fig_num,image_path,image_caption,golden_corpus,positive_corpus
Figure 19.1,cell_bio/images/Figure 19.1.jpg,Figure 19.1: Overview of the extracellular matrix.,"Structurally proteoglycans contain both proteins plus glycosaminoglycans (carbohydrates) and take on a bottle-brush structure (figure 19.1). They assemble into larger complexes, bound to a central hyaluronic acid. The overall structure is negatively charged, which attracts water, allowing it to function as a cushion.","{'b0871a89-2d06-48db-a376-ca140335415e': 'Structurally proteoglycans contain both proteins plus glycosaminoglycans (carbohydrates) and take on a bottle-brush structure (figure 19.1). They assemble into larger complexes, bound to a central hyaluronic acid. The overall structure is negatively charged, which attracts water, allowing it to function as a cushion.', '05b7b429-f7c4-4d24-8605-e9ecba289a5c': '19.1 References and resources', 'fb2083ca-79a2-4a58-9475-ef9550c8af16': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', '9714d027-8bc9-41fe-a60e-5beaef4509f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 7: Interactions between Cells and Their Environment.', '89475d98-4f42-4bb9-8069-aa6d7941f250': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 50–51.', '1097bc3e-f06c-4a29-864a-de482fbea113': 'The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).', '09a44727-5944-4178-965c-4d0737fb8dae': 'Microfilaments thicken the cortex around the cellʼs inner edge. Like rubber bands, they resist tension. There are microtubules in the cellʼs interior where they maintain their shape by resisting compressive forces. There are intermediate filaments throughout the cell that hold organelles in place.'}"
Figure 19.2,cell_bio/images/Figure 19.2.jpg,Figure 19.2: Schematic of integrin structure. The protein spans the plasma membrane and is an extracellular domain that can bind other matrix proteins.,Integrins span the plasma membrane and connect the matrix to the cellular environment (inside-out or outside-in signaling). They are associated with fibronectin (RGD sequences) on the extracellular side and have both active and inactive states (figure 19.2).,"{'c4c4ddaa-1c23-4573-885f-6b8df42e6944': 'Integrins span the plasma membrane and connect the matrix to the cellular environment (inside-out or outside-in signaling). They are associated with fibronectin (RGD sequences) on the extracellular side and have both active and inactive states (figure 19.2).', '05b7b429-f7c4-4d24-8605-e9ecba289a5c': '19.1 References and resources', 'fb2083ca-79a2-4a58-9475-ef9550c8af16': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', '9714d027-8bc9-41fe-a60e-5beaef4509f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 7: Interactions between Cells and Their Environment.', '89475d98-4f42-4bb9-8069-aa6d7941f250': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 50–51.', '1097bc3e-f06c-4a29-864a-de482fbea113': 'The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).', '09a44727-5944-4178-965c-4d0737fb8dae': 'Microfilaments thicken the cortex around the cellʼs inner edge. Like rubber bands, they resist tension. There are microtubules in the cellʼs interior where they maintain their shape by resisting compressive forces. There are intermediate filaments throughout the cell that hold organelles in place.'}"
Figure 19.3,cell_bio/images/Figure 19.3.jpg,Figure 19.3: Summary of cell adhesion mechanisms.,Focal adhesions and hemidesmosomes (figure 19.3) serve to anchor cells to the substratum.,"{'5e20a8af-bd88-4a9f-ba54-0e5f8f392ee1': 'Focal adhesions and hemidesmosomes (figure 19.3) serve to anchor cells to the substratum.', '0b87d11d-8d5b-40c4-92e5-646d1230a5b2': 'Focal adhesions are a cluster of rapidly assembling and disassembling proteins that involves a cluster of integrins connected to actin in the cytoskeleton.', 'c7fd4e83-ce7b-43a8-ab5c-553da706ecae': 'Hemidesmosomes are the tightest of all in vivo attachments. They consist of intermediate filaments (keratin) and form an attachment between the basal surface of epithelial cells to the basement membrane.', '05b7b429-f7c4-4d24-8605-e9ecba289a5c': '19.1 References and resources', 'fb2083ca-79a2-4a58-9475-ef9550c8af16': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', '9714d027-8bc9-41fe-a60e-5beaef4509f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 7: Interactions between Cells and Their Environment.', '89475d98-4f42-4bb9-8069-aa6d7941f250': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 50–51.', '1097bc3e-f06c-4a29-864a-de482fbea113': 'The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).', '09a44727-5944-4178-965c-4d0737fb8dae': 'Microfilaments thicken the cortex around the cellʼs inner edge. Like rubber bands, they resist tension. There are microtubules in the cellʼs interior where they maintain their shape by resisting compressive forces. There are intermediate filaments throughout the cell that hold organelles in place.'}"
Figure 19.1,cell_bio/images/Figure 19.1.jpg,Figure 19.1: Overview of the extracellular matrix.,"Structurally proteoglycans contain both proteins plus glycosaminoglycans (carbohydrates) and take on a bottle-brush structure (figure 19.1). They assemble into larger complexes, bound to a central hyaluronic acid. The overall structure is negatively charged, which attracts water, allowing it to function as a cushion.","{'b0871a89-2d06-48db-a376-ca140335415e': 'Structurally proteoglycans contain both proteins plus glycosaminoglycans (carbohydrates) and take on a bottle-brush structure (figure 19.1). They assemble into larger complexes, bound to a central hyaluronic acid. The overall structure is negatively charged, which attracts water, allowing it to function as a cushion.', '05b7b429-f7c4-4d24-8605-e9ecba289a5c': '19.1 References and resources', 'fb2083ca-79a2-4a58-9475-ef9550c8af16': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', '9714d027-8bc9-41fe-a60e-5beaef4509f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 7: Interactions between Cells and Their Environment.', '89475d98-4f42-4bb9-8069-aa6d7941f250': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 50–51.', '1097bc3e-f06c-4a29-864a-de482fbea113': 'The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).', '09a44727-5944-4178-965c-4d0737fb8dae': 'Microfilaments thicken the cortex around the cellʼs inner edge. Like rubber bands, they resist tension. There are microtubules in the cellʼs interior where they maintain their shape by resisting compressive forces. There are intermediate filaments throughout the cell that hold organelles in place.'}"
Figure 19.2,cell_bio/images/Figure 19.2.jpg,Figure 19.2: Schematic of integrin structure. The protein spans the plasma membrane and is an extracellular domain that can bind other matrix proteins.,Integrins span the plasma membrane and connect the matrix to the cellular environment (inside-out or outside-in signaling). They are associated with fibronectin (RGD sequences) on the extracellular side and have both active and inactive states (figure 19.2).,"{'c4c4ddaa-1c23-4573-885f-6b8df42e6944': 'Integrins span the plasma membrane and connect the matrix to the cellular environment (inside-out or outside-in signaling). They are associated with fibronectin (RGD sequences) on the extracellular side and have both active and inactive states (figure 19.2).', '05b7b429-f7c4-4d24-8605-e9ecba289a5c': '19.1 References and resources', 'fb2083ca-79a2-4a58-9475-ef9550c8af16': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', '9714d027-8bc9-41fe-a60e-5beaef4509f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 7: Interactions between Cells and Their Environment.', '89475d98-4f42-4bb9-8069-aa6d7941f250': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 50–51.', '1097bc3e-f06c-4a29-864a-de482fbea113': 'The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).', '09a44727-5944-4178-965c-4d0737fb8dae': 'Microfilaments thicken the cortex around the cellʼs inner edge. Like rubber bands, they resist tension. There are microtubules in the cellʼs interior where they maintain their shape by resisting compressive forces. There are intermediate filaments throughout the cell that hold organelles in place.'}"
Figure 19.3,cell_bio/images/Figure 19.3.jpg,Figure 19.3: Summary of cell adhesion mechanisms.,Focal adhesions and hemidesmosomes (figure 19.3) serve to anchor cells to the substratum.,"{'5e20a8af-bd88-4a9f-ba54-0e5f8f392ee1': 'Focal adhesions and hemidesmosomes (figure 19.3) serve to anchor cells to the substratum.', '0b87d11d-8d5b-40c4-92e5-646d1230a5b2': 'Focal adhesions are a cluster of rapidly assembling and disassembling proteins that involves a cluster of integrins connected to actin in the cytoskeleton.', 'c7fd4e83-ce7b-43a8-ab5c-553da706ecae': 'Hemidesmosomes are the tightest of all in vivo attachments. They consist of intermediate filaments (keratin) and form an attachment between the basal surface of epithelial cells to the basement membrane.', '05b7b429-f7c4-4d24-8605-e9ecba289a5c': '19.1 References and resources', 'fb2083ca-79a2-4a58-9475-ef9550c8af16': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', '9714d027-8bc9-41fe-a60e-5beaef4509f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 7: Interactions between Cells and Their Environment.', '89475d98-4f42-4bb9-8069-aa6d7941f250': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 50–51.', '1097bc3e-f06c-4a29-864a-de482fbea113': 'The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).', '09a44727-5944-4178-965c-4d0737fb8dae': 'Microfilaments thicken the cortex around the cellʼs inner edge. Like rubber bands, they resist tension. There are microtubules in the cellʼs interior where they maintain their shape by resisting compressive forces. There are intermediate filaments throughout the cell that hold organelles in place.'}"
Figure 18.2,cell_bio/images/Figure 18.2.jpg,"Figure 18.2: Spatial organization of the three types of fibers. Microfilaments thicken the cortex around the cell’s inner edge. Intermediate filaments have no role in cell movement. Their function is purely structural. They help the cell resist compression, provide a track along which vesicles move through the cell, and pull replicated chromosomes to opposite ends of a dividing cell.","The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).","{'05b7b429-f7c4-4d24-8605-e9ecba289a5c': '19.1 References and resources', 'fb2083ca-79a2-4a58-9475-ef9550c8af16': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', '9714d027-8bc9-41fe-a60e-5beaef4509f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 7: Interactions between Cells and Their Environment.', '89475d98-4f42-4bb9-8069-aa6d7941f250': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 50–51.', '1097bc3e-f06c-4a29-864a-de482fbea113': 'The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).', '09a44727-5944-4178-965c-4d0737fb8dae': 'Microfilaments thicken the cortex around the cellʼs inner edge. Like rubber bands, they resist tension. There are microtubules in the cellʼs interior where they maintain their shape by resisting compressive forces. There are intermediate filaments throughout the cell that hold organelles in place.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.', '6f43e8d0-d4c4-4374-a988-8df817adf5cc': 'Kinesin is a relatively small motor protein that moves membrane-bound cargo (e.g., vesicles). In contrast to dynein, most move toward the plus end β-tubulin) of the microtubules, which is typically away from the cell body. Figure 18.8 nicely summarizes the location and general role of each of these motor proteins.', '69f82ecb-d59a-4194-a202-44ced62a8233': '18.2 References and resources'}"
Figure 18.3,cell_bio/images/Figure 18.3.jpg,"Figure 18.3: Microfilaments are comprised of two globular protein intertwined strands, which we call actin. For this reason, we also call microfilaments actin filaments.","Of the three types of protein fibers in the cytoskeleton, microfilaments are the narrowest. They function in cellular movement, have a diameter of about 7 to 8 nm, and are comprised of two globular protein intertwined strands, which we call actin (figure 18.3). For this reason, we also call microfilaments actin filaments.","{'3112c05a-0535-4cc7-bf13-49e7a6be1d3f': 'Of the three types of protein fibers in the cytoskeleton, microfilaments are the narrowest. They function in cellular movement, have a diameter of about 7 to 8 nm, and are comprised of two globular protein intertwined strands, which we call actin (figure 18.3). For this reason, we also call microfilaments actin filaments.', '0907528b-eba0-4303-b1fc-1e30684edea4': 'ATP powers actin to assemble its filamentous form, which serves as a track for the movement of a motor protein we call myosin. This enables actin to engage in cellular events requiring motion, such as cell division in eukaryotic cells. Actin and myosin are plentiful in muscle cells.', 'ae9368ca-d113-44a6-9610-2c36c38cf551': 'Microfilaments also provide some rigidity and shape to the cell. They can depolymerize (disassemble) and reform quickly, thus enabling a cell to change its shape and move.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.'}"
Figure 18.4,cell_bio/images/Figure 18.4.jpg,Figure 18.4: Several strands of fibrous proteins that are wound together comprise intermediate filaments.,"Several strands of fibrous proteins that are wound together comprise intermediate filaments (figure 18.4). These cytoskeleton elements get their name from the fact that their diameter, 10 to 12 nm, is between those of microfilaments and microtubules.","{'2aa8d161-6203-4386-b283-24f5bd42a670': 'Several strands of fibrous proteins that are wound together comprise intermediate filaments (figure 18.4). These cytoskeleton elements get their name from the fact that their diameter, 10 to 12 nm, is between those of microfilaments and microtubules.', 'd1dccd26-9a40-494f-abcb-7c49affe18cd': 'Intermediate filaments have no role in cell movement. Their function is purely structural. They bear tension, thus maintaining the cellʼs shape, and anchor the nucleus and other organelles in place (figure 18.1).', '76215f44-8d54-4ed7-844a-fcf22411f661': 'The intermediate filaments are the most diverse group of cytoskeletal elements. They are unbranched and rope-like with long fibrous subunits. There is no polarity associated with their assembly. Intermediate filaments are classified by their location and function. The table below summarizes various types of intermediate filaments.', 'd6fef642-3bce-41a9-9c2c-11545bab765e': 'Table 18.1: Proteins and their functions.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.'}"
Figure 18.1,cell_bio/images/Figure 18.1.jpg,Figure 18.1: Summary of the three major types of structural filaments.,"Intermediate filaments have no role in cell movement. Their function is purely structural. They bear tension, thus maintaining the cellʼs shape, and anchor the nucleus and other organelles in place (figure 18.1).","{'2aa8d161-6203-4386-b283-24f5bd42a670': 'Several strands of fibrous proteins that are wound together comprise intermediate filaments (figure 18.4). These cytoskeleton elements get their name from the fact that their diameter, 10 to 12 nm, is between those of microfilaments and microtubules.', 'd1dccd26-9a40-494f-abcb-7c49affe18cd': 'Intermediate filaments have no role in cell movement. Their function is purely structural. They bear tension, thus maintaining the cellʼs shape, and anchor the nucleus and other organelles in place (figure 18.1).', '76215f44-8d54-4ed7-844a-fcf22411f661': 'The intermediate filaments are the most diverse group of cytoskeletal elements. They are unbranched and rope-like with long fibrous subunits. There is no polarity associated with their assembly. Intermediate filaments are classified by their location and function. The table below summarizes various types of intermediate filaments.', 'd6fef642-3bce-41a9-9c2c-11545bab765e': 'Table 18.1: Proteins and their functions.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.'}"
Figure 18.5,cell_bio/images/Figure 18.5.jpg,Figure 18.5: Microtubules are hollow. Their walls consist of thirteen polymerized dimers of α-tubulin and β-tubulin. The left image shows the tube’s molecular structure.,"As their name implies, microtubules are small hollow tubes. With a diameter of about 25 nm, microtubules are cytoskeletonsʼ widest components. They help the cell resist compression, provide a track along which vesicles move through the cell, and pull replicated chromosomes to opposite ends of a dividing cell (figure 18.5).","{'26b7f8b5-499b-4534-bb31-63250e654fc5': 'As their name implies, microtubules are small hollow tubes. With a diameter of about 25 nm, microtubules are cytoskeletonsʼ widest components. They help the cell resist compression, provide a track along which vesicles move through the cell, and pull replicated chromosomes to opposite ends of a dividing cell (figure 18.5).', 'a5907b4a-36a8-4a9c-b7be-6c5b8fd1e739': 'Like microfilaments, microtubules can disassemble and reform quickly using GTP. The tube is formed from polymerized dimers of α-tubulin and β-tubulin, two globular proteins. These proteins form long chains that comprise the microtubuleʼs walls. The assembly is slow and occurs from the plus end, which is designated by a row of β-tubulin. Disassembly can occur rapidly at the plus end. (Note the minus end has a row of α-tubulin.)', 'f26c84b4-a62f-4216-840c-00246af64a25': 'Microtubules are also the structural elements of flagella, cilia, and centrioles (the latter are the centrosomeʼs two perpendicular bodies). In animal cells, the centrosome is the microtubule-organizing center.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.'}"
Figure 18.6,cell_bio/images/Figure 18.6.jpg,Figure 18.6: This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet.,"Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).","{'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.'}"
Figure 18.1,cell_bio/images/Figure 18.1.jpg,Figure 18.1: Summary of the three major types of structural filaments.,"Intermediate filaments have no role in cell movement. Their function is purely structural. They bear tension, thus maintaining the cellʼs shape, and anchor the nucleus and other organelles in place (figure 18.1).","{'2aa8d161-6203-4386-b283-24f5bd42a670': 'Several strands of fibrous proteins that are wound together comprise intermediate filaments (figure 18.4). These cytoskeleton elements get their name from the fact that their diameter, 10 to 12 nm, is between those of microfilaments and microtubules.', 'd1dccd26-9a40-494f-abcb-7c49affe18cd': 'Intermediate filaments have no role in cell movement. Their function is purely structural. They bear tension, thus maintaining the cellʼs shape, and anchor the nucleus and other organelles in place (figure 18.1).', '76215f44-8d54-4ed7-844a-fcf22411f661': 'The intermediate filaments are the most diverse group of cytoskeletal elements. They are unbranched and rope-like with long fibrous subunits. There is no polarity associated with their assembly. Intermediate filaments are classified by their location and function. The table below summarizes various types of intermediate filaments.', 'd6fef642-3bce-41a9-9c2c-11545bab765e': 'Table 18.1: Proteins and their functions.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.'}"
Figure 18.2,cell_bio/images/Figure 18.2.jpg,"Figure 18.2: Spatial organization of the three types of fibers. Microfilaments thicken the cortex around the cell’s inner edge. Intermediate filaments have no role in cell movement. Their function is purely structural. They help the cell resist compression, provide a track along which vesicles move through the cell, and pull replicated chromosomes to opposite ends of a dividing cell.","The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).","{'05b7b429-f7c4-4d24-8605-e9ecba289a5c': '19.1 References and resources', 'fb2083ca-79a2-4a58-9475-ef9550c8af16': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', '9714d027-8bc9-41fe-a60e-5beaef4509f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 7: Interactions between Cells and Their Environment.', '89475d98-4f42-4bb9-8069-aa6d7941f250': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 50–51.', '1097bc3e-f06c-4a29-864a-de482fbea113': 'The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).', '09a44727-5944-4178-965c-4d0737fb8dae': 'Microfilaments thicken the cortex around the cellʼs inner edge. Like rubber bands, they resist tension. There are microtubules in the cellʼs interior where they maintain their shape by resisting compressive forces. There are intermediate filaments throughout the cell that hold organelles in place.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.', '6f43e8d0-d4c4-4374-a988-8df817adf5cc': 'Kinesin is a relatively small motor protein that moves membrane-bound cargo (e.g., vesicles). In contrast to dynein, most move toward the plus end β-tubulin) of the microtubules, which is typically away from the cell body. Figure 18.8 nicely summarizes the location and general role of each of these motor proteins.', '69f82ecb-d59a-4194-a202-44ced62a8233': '18.2 References and resources'}"
Figure 18.3,cell_bio/images/Figure 18.3.jpg,"Figure 18.3: Microfilaments are comprised of two globular protein intertwined strands, which we call actin. For this reason, we also call microfilaments actin filaments.","Of the three types of protein fibers in the cytoskeleton, microfilaments are the narrowest. They function in cellular movement, have a diameter of about 7 to 8 nm, and are comprised of two globular protein intertwined strands, which we call actin (figure 18.3). For this reason, we also call microfilaments actin filaments.","{'3112c05a-0535-4cc7-bf13-49e7a6be1d3f': 'Of the three types of protein fibers in the cytoskeleton, microfilaments are the narrowest. They function in cellular movement, have a diameter of about 7 to 8 nm, and are comprised of two globular protein intertwined strands, which we call actin (figure 18.3). For this reason, we also call microfilaments actin filaments.', '0907528b-eba0-4303-b1fc-1e30684edea4': 'ATP powers actin to assemble its filamentous form, which serves as a track for the movement of a motor protein we call myosin. This enables actin to engage in cellular events requiring motion, such as cell division in eukaryotic cells. Actin and myosin are plentiful in muscle cells.', 'ae9368ca-d113-44a6-9610-2c36c38cf551': 'Microfilaments also provide some rigidity and shape to the cell. They can depolymerize (disassemble) and reform quickly, thus enabling a cell to change its shape and move.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.'}"
Figure 18.4,cell_bio/images/Figure 18.4.jpg,Figure 18.4: Several strands of fibrous proteins that are wound together comprise intermediate filaments.,"Several strands of fibrous proteins that are wound together comprise intermediate filaments (figure 18.4). These cytoskeleton elements get their name from the fact that their diameter, 10 to 12 nm, is between those of microfilaments and microtubules.","{'2aa8d161-6203-4386-b283-24f5bd42a670': 'Several strands of fibrous proteins that are wound together comprise intermediate filaments (figure 18.4). These cytoskeleton elements get their name from the fact that their diameter, 10 to 12 nm, is between those of microfilaments and microtubules.', 'd1dccd26-9a40-494f-abcb-7c49affe18cd': 'Intermediate filaments have no role in cell movement. Their function is purely structural. They bear tension, thus maintaining the cellʼs shape, and anchor the nucleus and other organelles in place (figure 18.1).', '76215f44-8d54-4ed7-844a-fcf22411f661': 'The intermediate filaments are the most diverse group of cytoskeletal elements. They are unbranched and rope-like with long fibrous subunits. There is no polarity associated with their assembly. Intermediate filaments are classified by their location and function. The table below summarizes various types of intermediate filaments.', 'd6fef642-3bce-41a9-9c2c-11545bab765e': 'Table 18.1: Proteins and their functions.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.'}"
Figure 18.5,cell_bio/images/Figure 18.5.jpg,Figure 18.5: Microtubules are hollow. Their walls consist of thirteen polymerized dimers of α-tubulin and β-tubulin. The left image shows the tube’s molecular structure.,"As their name implies, microtubules are small hollow tubes. With a diameter of about 25 nm, microtubules are cytoskeletonsʼ widest components. They help the cell resist compression, provide a track along which vesicles move through the cell, and pull replicated chromosomes to opposite ends of a dividing cell (figure 18.5).","{'26b7f8b5-499b-4534-bb31-63250e654fc5': 'As their name implies, microtubules are small hollow tubes. With a diameter of about 25 nm, microtubules are cytoskeletonsʼ widest components. They help the cell resist compression, provide a track along which vesicles move through the cell, and pull replicated chromosomes to opposite ends of a dividing cell (figure 18.5).', 'a5907b4a-36a8-4a9c-b7be-6c5b8fd1e739': 'Like microfilaments, microtubules can disassemble and reform quickly using GTP. The tube is formed from polymerized dimers of α-tubulin and β-tubulin, two globular proteins. These proteins form long chains that comprise the microtubuleʼs walls. The assembly is slow and occurs from the plus end, which is designated by a row of β-tubulin. Disassembly can occur rapidly at the plus end. (Note the minus end has a row of α-tubulin.)', 'f26c84b4-a62f-4216-840c-00246af64a25': 'Microtubules are also the structural elements of flagella, cilia, and centrioles (the latter are the centrosomeʼs two perpendicular bodies). In animal cells, the centrosome is the microtubule-organizing center.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.'}"
Figure 18.7,cell_bio/images/Figure 18.7.jpg,Figure 18.7: Comparison of the three different motor proteins.,"Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.","{'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.', '6f43e8d0-d4c4-4374-a988-8df817adf5cc': 'Kinesin is a relatively small motor protein that moves membrane-bound cargo (e.g., vesicles). In contrast to dynein, most move toward the plus end β-tubulin) of the microtubules, which is typically away from the cell body. Figure 18.8 nicely summarizes the location and general role of each of these motor proteins.', '69f82ecb-d59a-4194-a202-44ced62a8233': '18.2 References and resources'}"
Figure 18.8,cell_bio/images/Figure 18.8.jpg,Figure 18.8: Summary of the roles and movement of the motor proteins along various cytoskeletal elements.,"Kinesin is a relatively small motor protein that moves membrane-bound cargo (e.g., vesicles). In contrast to dynein, most move toward the plus end β-tubulin) of the microtubules, which is typically away from the cell body. Figure 18.8 nicely summarizes the location and general role of each of these motor proteins.","{'6f43e8d0-d4c4-4374-a988-8df817adf5cc': 'Kinesin is a relatively small motor protein that moves membrane-bound cargo (e.g., vesicles). In contrast to dynein, most move toward the plus end β-tubulin) of the microtubules, which is typically away from the cell body. Figure 18.8 nicely summarizes the location and general role of each of these motor proteins.', '69f82ecb-d59a-4194-a202-44ced62a8233': '18.2 References and resources'}"
Figure 18.7,cell_bio/images/Figure 18.7.jpg,Figure 18.7: Comparison of the three different motor proteins.,"Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.","{'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.', '6f43e8d0-d4c4-4374-a988-8df817adf5cc': 'Kinesin is a relatively small motor protein that moves membrane-bound cargo (e.g., vesicles). In contrast to dynein, most move toward the plus end β-tubulin) of the microtubules, which is typically away from the cell body. Figure 18.8 nicely summarizes the location and general role of each of these motor proteins.', '69f82ecb-d59a-4194-a202-44ced62a8233': '18.2 References and resources'}"
Figure 18.2,cell_bio/images/Figure 18.2.jpg,"Figure 18.2: Spatial organization of the three types of fibers. Microfilaments thicken the cortex around the cell’s inner edge. Intermediate filaments have no role in cell movement. Their function is purely structural. They help the cell resist compression, provide a track along which vesicles move through the cell, and pull replicated chromosomes to opposite ends of a dividing cell.","The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).","{'05b7b429-f7c4-4d24-8605-e9ecba289a5c': '19.1 References and resources', 'fb2083ca-79a2-4a58-9475-ef9550c8af16': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', '9714d027-8bc9-41fe-a60e-5beaef4509f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 7: Interactions between Cells and Their Environment.', '89475d98-4f42-4bb9-8069-aa6d7941f250': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 50–51.', '1097bc3e-f06c-4a29-864a-de482fbea113': 'The collection of these fibers plays key roles in structure and support, intracellular transport, contractility and motility, as well as spacial organization (figure 18.2).', '09a44727-5944-4178-965c-4d0737fb8dae': 'Microfilaments thicken the cortex around the cellʼs inner edge. Like rubber bands, they resist tension. There are microtubules in the cellʼs interior where they maintain their shape by resisting compressive forces. There are intermediate filaments throughout the cell that hold organelles in place.', 'ffe12d1e-4b92-4b66-9e6e-23a8347017e7': 'The flagella (singular = flagellum) are long, hair-like structures that extend from the plasma membrane and enable an entire cell to move. When present, the cell has just one flagellum or a few flagella.', '87b0431a-fae2-4668-bf7e-d96bb4b3cdd9': 'However, when cilia (singular = cilium) are present, many of them extend along the plasma membraneʼs entire surface. They are short, hair-like structures that move entire cells (such as paramecia) or substances along the cellʼs outer surface (for example, the cilia of cells lining the Fallopian tubes that move the ovum toward the uterus, or cilia lining the cells of the respiratory tract that trap particulate matter and move it toward your nostrils).', '282b3b9b-78d6-46ee-87f1-eed28c5106e8': 'Despite their differences in length and number, flagella and cilia share a common structural arrangement of microtubules called a “9 + 2 array.” This is an appropriate name because a single flagellum or cilium is made of a ring of nine microtubule doublets, surrounding a single microtubule doublet (axoneme) in the center (figure 18.6).', '726f254e-67ce-4609-8923-825fe56deb98': '18.1 References and resources', '8de04fb4-faa7-4d1a-9014-9ecd3be6078f': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 4: Cell Structure, Chapter 5: Structure and Function of the Plasma Membranes.', 'e8f59ea5-e5a2-48f7-9b0e-4623c1ff2211': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 9: The Cytoskeleton and Cell Mobility.', '9609c241-c248-44a9-93de-77484094e4c2': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 48–49.', '83d045d4-a113-419a-a82e-b49114ab94d1': 'Dartmouth Electron Microscope Facility, Dartmouth College. Figure 18.6 This transmission electron micrograph of two flagella shows the microtubules’ 9 + 2 array: nine microtubule doublets surround a single microtubule doublet. Scale bar data from Matt Russell. Public domain. From Wikimedia Commons.', '0a91747f-a15f-400e-a97e-bf1356d4568c': '18.2 Cell Movement', '488828ca-11e2-4912-8264-91505ead7037': 'Motor proteins, such as myosins, dyneins, and kinesins (figure 18.7), move along cytoskeletal filaments via a force-dependent mechanism that is driven by the hydrolysis of ATP molecules. Motor proteins propel themselves along the cytoskeleton using a mechanochemical cycle of filament binding, conformational change, filament release, conformation reversal, and filament rebinding. In most cases, the conformational change(s) on the motor protein prevents subsequent nucleotide binding or hydrolysis until the prior round of hydrolysis and release is complete.', '6f43e8d0-d4c4-4374-a988-8df817adf5cc': 'Kinesin is a relatively small motor protein that moves membrane-bound cargo (e.g., vesicles). In contrast to dynein, most move toward the plus end β-tubulin) of the microtubules, which is typically away from the cell body. Figure 18.8 nicely summarizes the location and general role of each of these motor proteins.', '69f82ecb-d59a-4194-a202-44ced62a8233': '18.2 References and resources'}"
Figure 17.1,cell_bio/images/Figure 17.1.jpg,Figure 17.1: EM of the nucleus and nucleolus.,"Inside the nuclear envelope is a gel-like nucleoplasm with solutes that include the building blocks of nucleic acids. There also can be a dark-staining mass often visible under a simple light microscope, called a nucleolus (plural = nucleoli). The nucleolus is a region of the nucleus that is responsible for manufacturing the RNA necessary for construction of ribosomes. Once synthesized, newly made ribosomal subunits exit the cellʼs nucleus through the nuclear pores (figure 17.1). Proteins entering the nucleus require nuclear localization signals, while proteins exiting require nuclear export signals.","{'5fd5e4cd-b544-48af-8a83-cc519f8c4113': 'Proteins called pore complexes lining the nuclear pores regulate the passage of materials into and out of the nucleus.', '3b2d10f2-7d09-4392-aeea-565cefd9e45a': 'Inside the nuclear envelope is a gel-like nucleoplasm with solutes that include the building blocks of nucleic acids. There also can be a dark-staining mass often visible under a simple light microscope, called a nucleolus (plural = nucleoli). The nucleolus is a region of the nucleus that is responsible for manufacturing the RNA necessary for construction of ribosomes. Once synthesized, newly made ribosomal subunits exit the cellʼs nucleus through the nuclear pores (figure 17.1). Proteins entering the nucleus require nuclear localization signals, while proteins exiting require nuclear export signals.', 'cd2a48c5-bbf1-4e75-bef4-83bb25040bc2': 'Lysosomes are organelles formed by the fusion of a late endosome\xa0and a lysosomal-enzyme-filled vesicle secreted from the Golgi. Proteins are targeted to lysosomes by the\xa0presence of mannose 6-phosphate (acquired in the RER), and the presence of these tags are essential for trafficking to the lysosome.', '722394f9-21c2-47f4-983e-30675bbd6068': 'The major function for these organelles is to break down macromolecules through enzymatic degradation. Both processes of autophagy and exocytosis can be facilitated. Lysosomal storage diseases are inherited metabolic diseases characterized by an abnormal buildup of various metabolic intermediates. Collectively, there are approximately fifty\xa0of these disorders, and they may affect different parts of the body. Clinical correlates include: Gaucher disease, Fabry disease, glycogen storage disease, mucopolisacaridosis, and sphingolipidoses.', '462eb4c5-ee3b-4e93-a06a-8907a5112b10': 'This is in contrast to peroxisomes, which are formed by budding from the ER. They primarily perform hydrogen peroxide-mediated degradation of lipids (i.e., very long-chain fatty acids) and some amino acids. Zellweger syndrome is one of the heritable disorders of peroxisome biogenesis and results in infant death before six\xa0months.', '4df50db6-2c03-4953-9886-3476f69bb217': '17.1 References and resources', '4cc4c798-c137-4039-8a5c-b9720561a1d2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '8519085e-908b-4ed1-a45f-7e8e69294a2d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.'}"
Figure 17.2,cell_bio/images/Figure 17.2.jpg,Figure 17.2: Interaction of the endomembrane systems.,"The endomembrane system (endo = “within”) is a group of membranes and organelles (figure 17.2) in eukaryotic cells that work together to modify, package, and transport lipids and proteins. It includes the nuclear envelope as well as:","{'43649321-a9b3-44c6-8292-c87d85fbfaa7': 'The endomembrane system (endo = “within”) is a group of membranes and organelles (figure 17.2) in eukaryotic cells that work\xa0together to modify, package, and transport lipids and proteins. It includes the nuclear envelope as well as:', 'e0073d76-09c7-4f11-a795-5528a0bacc87': 'Although not technically within the cell\xa0the plasma membrane is included in the endomembrane system because, it interacts with the other endomembranous organelles. The endomembrane system does not include the mitochondria. The system of intracellular membranes is designed to move proteins through both the secretory pathway (constitutive or regulated) and the endocytic pathways.', '1cbd75ac-8c6e-4ef3-8625-1132b2949f66': 'The endoplasmic reticulum (ER) (figure 17.2) is a series of interconnected membranous sacs and tubules that collectively modify\xa0proteins and synthesize\xa0lipids. However, these two functions take place in separate areas of the ER: the rough ER and the smooth ER, respectively.', 'cd2a48c5-bbf1-4e75-bef4-83bb25040bc2': 'Lysosomes are organelles formed by the fusion of a late endosome\xa0and a lysosomal-enzyme-filled vesicle secreted from the Golgi. Proteins are targeted to lysosomes by the\xa0presence of mannose 6-phosphate (acquired in the RER), and the presence of these tags are essential for trafficking to the lysosome.', '722394f9-21c2-47f4-983e-30675bbd6068': 'The major function for these organelles is to break down macromolecules through enzymatic degradation. Both processes of autophagy and exocytosis can be facilitated. Lysosomal storage diseases are inherited metabolic diseases characterized by an abnormal buildup of various metabolic intermediates. Collectively, there are approximately fifty\xa0of these disorders, and they may affect different parts of the body. Clinical correlates include: Gaucher disease, Fabry disease, glycogen storage disease, mucopolisacaridosis, and sphingolipidoses.', '462eb4c5-ee3b-4e93-a06a-8907a5112b10': 'This is in contrast to peroxisomes, which are formed by budding from the ER. They primarily perform hydrogen peroxide-mediated degradation of lipids (i.e., very long-chain fatty acids) and some amino acids. Zellweger syndrome is one of the heritable disorders of peroxisome biogenesis and results in infant death before six\xa0months.', '4df50db6-2c03-4953-9886-3476f69bb217': '17.1 References and resources', '4cc4c798-c137-4039-8a5c-b9720561a1d2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '8519085e-908b-4ed1-a45f-7e8e69294a2d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.'}"
Figure 17.2,cell_bio/images/Figure 17.2.jpg,Figure 17.2: Interaction of the endomembrane systems.,"The endomembrane system (endo = “within”) is a group of membranes and organelles (figure 17.2) in eukaryotic cells that work together to modify, package, and transport lipids and proteins. It includes the nuclear envelope as well as:","{'43649321-a9b3-44c6-8292-c87d85fbfaa7': 'The endomembrane system (endo = “within”) is a group of membranes and organelles (figure 17.2) in eukaryotic cells that work\xa0together to modify, package, and transport lipids and proteins. It includes the nuclear envelope as well as:', 'e0073d76-09c7-4f11-a795-5528a0bacc87': 'Although not technically within the cell\xa0the plasma membrane is included in the endomembrane system because, it interacts with the other endomembranous organelles. The endomembrane system does not include the mitochondria. The system of intracellular membranes is designed to move proteins through both the secretory pathway (constitutive or regulated) and the endocytic pathways.', '1cbd75ac-8c6e-4ef3-8625-1132b2949f66': 'The endoplasmic reticulum (ER) (figure 17.2) is a series of interconnected membranous sacs and tubules that collectively modify\xa0proteins and synthesize\xa0lipids. However, these two functions take place in separate areas of the ER: the rough ER and the smooth ER, respectively.', 'cd2a48c5-bbf1-4e75-bef4-83bb25040bc2': 'Lysosomes are organelles formed by the fusion of a late endosome\xa0and a lysosomal-enzyme-filled vesicle secreted from the Golgi. Proteins are targeted to lysosomes by the\xa0presence of mannose 6-phosphate (acquired in the RER), and the presence of these tags are essential for trafficking to the lysosome.', '722394f9-21c2-47f4-983e-30675bbd6068': 'The major function for these organelles is to break down macromolecules through enzymatic degradation. Both processes of autophagy and exocytosis can be facilitated. Lysosomal storage diseases are inherited metabolic diseases characterized by an abnormal buildup of various metabolic intermediates. Collectively, there are approximately fifty\xa0of these disorders, and they may affect different parts of the body. Clinical correlates include: Gaucher disease, Fabry disease, glycogen storage disease, mucopolisacaridosis, and sphingolipidoses.', '462eb4c5-ee3b-4e93-a06a-8907a5112b10': 'This is in contrast to peroxisomes, which are formed by budding from the ER. They primarily perform hydrogen peroxide-mediated degradation of lipids (i.e., very long-chain fatty acids) and some amino acids. Zellweger syndrome is one of the heritable disorders of peroxisome biogenesis and results in infant death before six\xa0months.', '4df50db6-2c03-4953-9886-3476f69bb217': '17.1 References and resources', '4cc4c798-c137-4039-8a5c-b9720561a1d2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '8519085e-908b-4ed1-a45f-7e8e69294a2d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.'}"
Figure 17.3,cell_bio/images/Figure 17.3.jpg,Figure 17.3: Unfolded protein response in the RER.,"If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).","{'49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).', 'cd2a48c5-bbf1-4e75-bef4-83bb25040bc2': 'Lysosomes are organelles formed by the fusion of a late endosome\xa0and a lysosomal-enzyme-filled vesicle secreted from the Golgi. Proteins are targeted to lysosomes by the\xa0presence of mannose 6-phosphate (acquired in the RER), and the presence of these tags are essential for trafficking to the lysosome.', '722394f9-21c2-47f4-983e-30675bbd6068': 'The major function for these organelles is to break down macromolecules through enzymatic degradation. Both processes of autophagy and exocytosis can be facilitated. Lysosomal storage diseases are inherited metabolic diseases characterized by an abnormal buildup of various metabolic intermediates. Collectively, there are approximately fifty\xa0of these disorders, and they may affect different parts of the body. Clinical correlates include: Gaucher disease, Fabry disease, glycogen storage disease, mucopolisacaridosis, and sphingolipidoses.', '462eb4c5-ee3b-4e93-a06a-8907a5112b10': 'This is in contrast to peroxisomes, which are formed by budding from the ER. They primarily perform hydrogen peroxide-mediated degradation of lipids (i.e., very long-chain fatty acids) and some amino acids. Zellweger syndrome is one of the heritable disorders of peroxisome biogenesis and results in infant death before six\xa0months.', '4df50db6-2c03-4953-9886-3476f69bb217': '17.1 References and resources', '4cc4c798-c137-4039-8a5c-b9720561a1d2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '8519085e-908b-4ed1-a45f-7e8e69294a2d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.'}"
Figure 17.2,cell_bio/images/Figure 17.2.jpg,Figure 17.2: Interaction of the endomembrane systems.,"The endomembrane system (endo = “within”) is a group of membranes and organelles (figure 17.2) in eukaryotic cells that work together to modify, package, and transport lipids and proteins. It includes the nuclear envelope as well as:","{'43649321-a9b3-44c6-8292-c87d85fbfaa7': 'The endomembrane system (endo = “within”) is a group of membranes and organelles (figure 17.2) in eukaryotic cells that work\xa0together to modify, package, and transport lipids and proteins. It includes the nuclear envelope as well as:', 'e0073d76-09c7-4f11-a795-5528a0bacc87': 'Although not technically within the cell\xa0the plasma membrane is included in the endomembrane system because, it interacts with the other endomembranous organelles. The endomembrane system does not include the mitochondria. The system of intracellular membranes is designed to move proteins through both the secretory pathway (constitutive or regulated) and the endocytic pathways.', '1cbd75ac-8c6e-4ef3-8625-1132b2949f66': 'The endoplasmic reticulum (ER) (figure 17.2) is a series of interconnected membranous sacs and tubules that collectively modify\xa0proteins and synthesize\xa0lipids. However, these two functions take place in separate areas of the ER: the rough ER and the smooth ER, respectively.', 'cd2a48c5-bbf1-4e75-bef4-83bb25040bc2': 'Lysosomes are organelles formed by the fusion of a late endosome\xa0and a lysosomal-enzyme-filled vesicle secreted from the Golgi. Proteins are targeted to lysosomes by the\xa0presence of mannose 6-phosphate (acquired in the RER), and the presence of these tags are essential for trafficking to the lysosome.', '722394f9-21c2-47f4-983e-30675bbd6068': 'The major function for these organelles is to break down macromolecules through enzymatic degradation. Both processes of autophagy and exocytosis can be facilitated. Lysosomal storage diseases are inherited metabolic diseases characterized by an abnormal buildup of various metabolic intermediates. Collectively, there are approximately fifty\xa0of these disorders, and they may affect different parts of the body. Clinical correlates include: Gaucher disease, Fabry disease, glycogen storage disease, mucopolisacaridosis, and sphingolipidoses.', '462eb4c5-ee3b-4e93-a06a-8907a5112b10': 'This is in contrast to peroxisomes, which are formed by budding from the ER. They primarily perform hydrogen peroxide-mediated degradation of lipids (i.e., very long-chain fatty acids) and some amino acids. Zellweger syndrome is one of the heritable disorders of peroxisome biogenesis and results in infant death before six\xa0months.', '4df50db6-2c03-4953-9886-3476f69bb217': '17.1 References and resources', '4cc4c798-c137-4039-8a5c-b9720561a1d2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '8519085e-908b-4ed1-a45f-7e8e69294a2d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.'}"
Figure 17.3,cell_bio/images/Figure 17.3.jpg,Figure 17.3: Unfolded protein response in the RER.,"If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).","{'49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).', 'cd2a48c5-bbf1-4e75-bef4-83bb25040bc2': 'Lysosomes are organelles formed by the fusion of a late endosome\xa0and a lysosomal-enzyme-filled vesicle secreted from the Golgi. Proteins are targeted to lysosomes by the\xa0presence of mannose 6-phosphate (acquired in the RER), and the presence of these tags are essential for trafficking to the lysosome.', '722394f9-21c2-47f4-983e-30675bbd6068': 'The major function for these organelles is to break down macromolecules through enzymatic degradation. Both processes of autophagy and exocytosis can be facilitated. Lysosomal storage diseases are inherited metabolic diseases characterized by an abnormal buildup of various metabolic intermediates. Collectively, there are approximately fifty\xa0of these disorders, and they may affect different parts of the body. Clinical correlates include: Gaucher disease, Fabry disease, glycogen storage disease, mucopolisacaridosis, and sphingolipidoses.', '462eb4c5-ee3b-4e93-a06a-8907a5112b10': 'This is in contrast to peroxisomes, which are formed by budding from the ER. They primarily perform hydrogen peroxide-mediated degradation of lipids (i.e., very long-chain fatty acids) and some amino acids. Zellweger syndrome is one of the heritable disorders of peroxisome biogenesis and results in infant death before six\xa0months.', '4df50db6-2c03-4953-9886-3476f69bb217': '17.1 References and resources', '4cc4c798-c137-4039-8a5c-b9720561a1d2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '8519085e-908b-4ed1-a45f-7e8e69294a2d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.'}"
Figure 17.1,cell_bio/images/Figure 17.1.jpg,Figure 17.1: EM of the nucleus and nucleolus.,"Inside the nuclear envelope is a gel-like nucleoplasm with solutes that include the building blocks of nucleic acids. There also can be a dark-staining mass often visible under a simple light microscope, called a nucleolus (plural = nucleoli). The nucleolus is a region of the nucleus that is responsible for manufacturing the RNA necessary for construction of ribosomes. Once synthesized, newly made ribosomal subunits exit the cellʼs nucleus through the nuclear pores (figure 17.1). Proteins entering the nucleus require nuclear localization signals, while proteins exiting require nuclear export signals.","{'5fd5e4cd-b544-48af-8a83-cc519f8c4113': 'Proteins called pore complexes lining the nuclear pores regulate the passage of materials into and out of the nucleus.', '3b2d10f2-7d09-4392-aeea-565cefd9e45a': 'Inside the nuclear envelope is a gel-like nucleoplasm with solutes that include the building blocks of nucleic acids. There also can be a dark-staining mass often visible under a simple light microscope, called a nucleolus (plural = nucleoli). The nucleolus is a region of the nucleus that is responsible for manufacturing the RNA necessary for construction of ribosomes. Once synthesized, newly made ribosomal subunits exit the cellʼs nucleus through the nuclear pores (figure 17.1). Proteins entering the nucleus require nuclear localization signals, while proteins exiting require nuclear export signals.', 'cd2a48c5-bbf1-4e75-bef4-83bb25040bc2': 'Lysosomes are organelles formed by the fusion of a late endosome\xa0and a lysosomal-enzyme-filled vesicle secreted from the Golgi. Proteins are targeted to lysosomes by the\xa0presence of mannose 6-phosphate (acquired in the RER), and the presence of these tags are essential for trafficking to the lysosome.', '722394f9-21c2-47f4-983e-30675bbd6068': 'The major function for these organelles is to break down macromolecules through enzymatic degradation. Both processes of autophagy and exocytosis can be facilitated. Lysosomal storage diseases are inherited metabolic diseases characterized by an abnormal buildup of various metabolic intermediates. Collectively, there are approximately fifty\xa0of these disorders, and they may affect different parts of the body. Clinical correlates include: Gaucher disease, Fabry disease, glycogen storage disease, mucopolisacaridosis, and sphingolipidoses.', '462eb4c5-ee3b-4e93-a06a-8907a5112b10': 'This is in contrast to peroxisomes, which are formed by budding from the ER. They primarily perform hydrogen peroxide-mediated degradation of lipids (i.e., very long-chain fatty acids) and some amino acids. Zellweger syndrome is one of the heritable disorders of peroxisome biogenesis and results in infant death before six\xa0months.', '4df50db6-2c03-4953-9886-3476f69bb217': '17.1 References and resources', '4cc4c798-c137-4039-8a5c-b9720561a1d2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '8519085e-908b-4ed1-a45f-7e8e69294a2d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.'}"
Figure 17.4,cell_bio/images/Figure 17.4.jpg,"Figure 17.4: General process of phagocytosis. In phagocytosis, the cell membrane surrounds the particle and engulfs it.","Phagocytosis (the condition of “cell eating”) is the process by which a cell takes in large particles, such as other cells or relatively large particles. For example, when microorganisms invade the human body, a type of white blood cell, a neutrophil, will remove the invaders through this process, surrounding and engulfing the microorganism, which the neutrophil then destroys (figure 17.4).","{'7185bf0c-2836-421b-966d-d3309ff13fb8': 'Phagocytosis (the condition of “cell eating”) is the process by which a cell takes in large particles, such as other cells or relatively large particles. For example, when microorganisms invade the human body, a type of white blood cell, a neutrophil, will remove the invaders through this process, surrounding and engulfing the microorganism, which the neutrophil then destroys (figure 17.4).', 'bb1645a6-55ef-4042-baff-74ace4610d0f': 'In preparation for phagocytosis, a portion of the plasma membraneʼs inward-facing surface becomes coated with the protein clathrin, which stabilizes this membraneʼs section. The membraneʼs coated portion then extends from the cellʼs body and surrounds the particle, eventually enclosing it. Once the vesicle containing the particle is enclosed within the cell, the clathrin disengages from the membrane ,and the vesicle merges with a lysosome for breaking down the material in the newly formed compartment (endosome). When accessible nutrients from the vesicular contentsʼ degradation have been extracted, the newly formed endosome merges with the plasma membrane and releases its contents into the extracellular fluid. The endosomal membrane again becomes part of the plasma membrane.', '5a2bb561-1157-46d0-8de7-449c7e6fcbac': 'Exocytosis is the opposite of the processes we discussed above in that its purpose is to expel material from the cell into the extracellular fluid. Waste material is enveloped in a membrane and fuses with the plasma membraneʼs interior. This fusion opens the membranous envelope on the cellʼs exterior, and the waste material expels into the extracellular space. Other examples of cells releasing molecules via exocytosis include extracellular matrix protein secretion and neurotransmitter secretion into the synaptic cleft by synaptic vesicles (figure 17.6).', 'dafc7e66-578a-4b3f-b0ed-72310debe357': '17.2 References and resources', '852c5438-5d39-4c8a-b176-1e67625ba63c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '281f0c74-291c-4ff9-821c-fb7da8f3c2b4': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.', 'c9f95463-d7b4-4a70-8691-e9b32dda0cb9': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.4 General process of phagocytosis… Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 308. Figure 8.46 A summary of phagocytic pathway. 2014.', '740bae32-2822-46e4-ae64-f54d07e8cd7b': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.5 Receptor mediated endocytosis, LDL-receptor is a classic example of this process. Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 306. Figure 8.42 The endocytic pathway. 2014.', '017d18f8-e904-4371-905c-c35b23a07117': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.6 Exocytosis: vesicles containing substances fuse with the plasma membrane… Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 299. Figure 35 A summary of the autophagic pathway. 2014.'}"
Figure 17.5,cell_bio/images/Figure 17.5.jpg,Figure 17.5: Receptor-mediated endocytosis; LDL receptor is a classic example of this process.,A targeted variation of endocytosis employs receptor proteins in the plasma membrane that have a specific binding affinity for certain substances (figure 17.5).,"{'0f6add49-23d9-4f4a-ad74-d2d3b7d75e85': 'A targeted variation of endocytosis employs receptor proteins in the plasma membrane that have a specific binding affinity for certain substances (figure 17.5).', '7fc6efd2-6812-4c10-85fb-254e01d94173': 'In receptor-mediated endocytosis, the cellʼs uptake of substances targets a single type of substance that binds to the receptor on the cell membraneʼs external surface.', 'c4fbf4db-6b52-43ac-8f82-59b9d3d706e6': 'Clathrin attaches to the plasma membraneʼs cytoplasmic side. If a compoundʼs uptake is dependent on receptor-mediated endocytosis and the process is ineffective, the material will not be removed from the tissue fluids or blood. Instead, it will stay in those fluids and increase in concentration. The failure of receptor-mediated endocytosis causes some human diseases.', '206db806-138f-46ac-9292-6ece23934ac7': 'For example, receptor-mediated endocytosis removes low-density lipoprotein or LDL from the blood. In the human genetic disease familial hypercholesterolemia, the LDL receptors are defective or missing entirely. People with this condition have life-threatening levels of cholesterol in their blood\xa0because their cells cannot clear LDL particles. See chapter\xa06.', '5a2bb561-1157-46d0-8de7-449c7e6fcbac': 'Exocytosis is the opposite of the processes we discussed above in that its purpose is to expel material from the cell into the extracellular fluid. Waste material is enveloped in a membrane and fuses with the plasma membraneʼs interior. This fusion opens the membranous envelope on the cellʼs exterior, and the waste material expels into the extracellular space. Other examples of cells releasing molecules via exocytosis include extracellular matrix protein secretion and neurotransmitter secretion into the synaptic cleft by synaptic vesicles (figure 17.6).', 'dafc7e66-578a-4b3f-b0ed-72310debe357': '17.2 References and resources', '852c5438-5d39-4c8a-b176-1e67625ba63c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '281f0c74-291c-4ff9-821c-fb7da8f3c2b4': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.', 'c9f95463-d7b4-4a70-8691-e9b32dda0cb9': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.4 General process of phagocytosis… Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 308. Figure 8.46 A summary of phagocytic pathway. 2014.', '740bae32-2822-46e4-ae64-f54d07e8cd7b': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.5 Receptor mediated endocytosis, LDL-receptor is a classic example of this process. Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 306. Figure 8.42 The endocytic pathway. 2014.', '017d18f8-e904-4371-905c-c35b23a07117': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.6 Exocytosis: vesicles containing substances fuse with the plasma membrane… Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 299. Figure 35 A summary of the autophagic pathway. 2014.'}"
Figure 17.6,cell_bio/images/Figure 17.6.jpg,Figure 17.6: Exocytosis: vesicles containing substances fuse with the plasma membrane. The contents then release to the cell’s exterior.,"Exocytosis is the opposite of the processes we discussed above in that its purpose is to expel material from the cell into the extracellular fluid. Waste material is enveloped in a membrane and fuses with the plasma membraneʼs interior. This fusion opens the membranous envelope on the cellʼs exterior, and the waste material expels into the extracellular space. Other examples of cells releasing molecules via exocytosis include extracellular matrix protein secretion and neurotransmitter secretion into the synaptic cleft by synaptic vesicles (figure 17.6).","{'5a2bb561-1157-46d0-8de7-449c7e6fcbac': 'Exocytosis is the opposite of the processes we discussed above in that its purpose is to expel material from the cell into the extracellular fluid. Waste material is enveloped in a membrane and fuses with the plasma membraneʼs interior. This fusion opens the membranous envelope on the cellʼs exterior, and the waste material expels into the extracellular space. Other examples of cells releasing molecules via exocytosis include extracellular matrix protein secretion and neurotransmitter secretion into the synaptic cleft by synaptic vesicles (figure 17.6).', 'dafc7e66-578a-4b3f-b0ed-72310debe357': '17.2 References and resources', '852c5438-5d39-4c8a-b176-1e67625ba63c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '281f0c74-291c-4ff9-821c-fb7da8f3c2b4': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.', 'c9f95463-d7b4-4a70-8691-e9b32dda0cb9': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.4 General process of phagocytosis… Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 308. Figure 8.46 A summary of phagocytic pathway. 2014.', '740bae32-2822-46e4-ae64-f54d07e8cd7b': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.5 Receptor mediated endocytosis, LDL-receptor is a classic example of this process. Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 306. Figure 8.42 The endocytic pathway. 2014.', '017d18f8-e904-4371-905c-c35b23a07117': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.6 Exocytosis: vesicles containing substances fuse with the plasma membrane… Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 299. Figure 35 A summary of the autophagic pathway. 2014.'}"
Figure 17.4,cell_bio/images/Figure 17.4.jpg,"Figure 17.4: General process of phagocytosis. In phagocytosis, the cell membrane surrounds the particle and engulfs it.","Phagocytosis (the condition of “cell eating”) is the process by which a cell takes in large particles, such as other cells or relatively large particles. For example, when microorganisms invade the human body, a type of white blood cell, a neutrophil, will remove the invaders through this process, surrounding and engulfing the microorganism, which the neutrophil then destroys (figure 17.4).","{'7185bf0c-2836-421b-966d-d3309ff13fb8': 'Phagocytosis (the condition of “cell eating”) is the process by which a cell takes in large particles, such as other cells or relatively large particles. For example, when microorganisms invade the human body, a type of white blood cell, a neutrophil, will remove the invaders through this process, surrounding and engulfing the microorganism, which the neutrophil then destroys (figure 17.4).', 'bb1645a6-55ef-4042-baff-74ace4610d0f': 'In preparation for phagocytosis, a portion of the plasma membraneʼs inward-facing surface becomes coated with the protein clathrin, which stabilizes this membraneʼs section. The membraneʼs coated portion then extends from the cellʼs body and surrounds the particle, eventually enclosing it. Once the vesicle containing the particle is enclosed within the cell, the clathrin disengages from the membrane ,and the vesicle merges with a lysosome for breaking down the material in the newly formed compartment (endosome). When accessible nutrients from the vesicular contentsʼ degradation have been extracted, the newly formed endosome merges with the plasma membrane and releases its contents into the extracellular fluid. The endosomal membrane again becomes part of the plasma membrane.', '5a2bb561-1157-46d0-8de7-449c7e6fcbac': 'Exocytosis is the opposite of the processes we discussed above in that its purpose is to expel material from the cell into the extracellular fluid. Waste material is enveloped in a membrane and fuses with the plasma membraneʼs interior. This fusion opens the membranous envelope on the cellʼs exterior, and the waste material expels into the extracellular space. Other examples of cells releasing molecules via exocytosis include extracellular matrix protein secretion and neurotransmitter secretion into the synaptic cleft by synaptic vesicles (figure 17.6).', 'dafc7e66-578a-4b3f-b0ed-72310debe357': '17.2 References and resources', '852c5438-5d39-4c8a-b176-1e67625ba63c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '281f0c74-291c-4ff9-821c-fb7da8f3c2b4': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.', 'c9f95463-d7b4-4a70-8691-e9b32dda0cb9': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.4 General process of phagocytosis… Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 308. Figure 8.46 A summary of phagocytic pathway. 2014.', '740bae32-2822-46e4-ae64-f54d07e8cd7b': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.5 Receptor mediated endocytosis, LDL-receptor is a classic example of this process. Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 306. Figure 8.42 The endocytic pathway. 2014.', '017d18f8-e904-4371-905c-c35b23a07117': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.6 Exocytosis: vesicles containing substances fuse with the plasma membrane… Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 299. Figure 35 A summary of the autophagic pathway. 2014.'}"
Figure 17.5,cell_bio/images/Figure 17.5.jpg,Figure 17.5: Receptor-mediated endocytosis; LDL receptor is a classic example of this process.,A targeted variation of endocytosis employs receptor proteins in the plasma membrane that have a specific binding affinity for certain substances (figure 17.5).,"{'0f6add49-23d9-4f4a-ad74-d2d3b7d75e85': 'A targeted variation of endocytosis employs receptor proteins in the plasma membrane that have a specific binding affinity for certain substances (figure 17.5).', '7fc6efd2-6812-4c10-85fb-254e01d94173': 'In receptor-mediated endocytosis, the cellʼs uptake of substances targets a single type of substance that binds to the receptor on the cell membraneʼs external surface.', 'c4fbf4db-6b52-43ac-8f82-59b9d3d706e6': 'Clathrin attaches to the plasma membraneʼs cytoplasmic side. If a compoundʼs uptake is dependent on receptor-mediated endocytosis and the process is ineffective, the material will not be removed from the tissue fluids or blood. Instead, it will stay in those fluids and increase in concentration. The failure of receptor-mediated endocytosis causes some human diseases.', '206db806-138f-46ac-9292-6ece23934ac7': 'For example, receptor-mediated endocytosis removes low-density lipoprotein or LDL from the blood. In the human genetic disease familial hypercholesterolemia, the LDL receptors are defective or missing entirely. People with this condition have life-threatening levels of cholesterol in their blood\xa0because their cells cannot clear LDL particles. See chapter\xa06.', '5a2bb561-1157-46d0-8de7-449c7e6fcbac': 'Exocytosis is the opposite of the processes we discussed above in that its purpose is to expel material from the cell into the extracellular fluid. Waste material is enveloped in a membrane and fuses with the plasma membraneʼs interior. This fusion opens the membranous envelope on the cellʼs exterior, and the waste material expels into the extracellular space. Other examples of cells releasing molecules via exocytosis include extracellular matrix protein secretion and neurotransmitter secretion into the synaptic cleft by synaptic vesicles (figure 17.6).', 'dafc7e66-578a-4b3f-b0ed-72310debe357': '17.2 References and resources', '852c5438-5d39-4c8a-b176-1e67625ba63c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 8: Cytoplasmic Membrane Systems: Structure, Function, and Membrane Trafficking.', '281f0c74-291c-4ff9-821c-fb7da8f3c2b4': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 46–47.', 'c9f95463-d7b4-4a70-8691-e9b32dda0cb9': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.4 General process of phagocytosis… Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 308. Figure 8.46 A summary of phagocytic pathway. 2014.', '740bae32-2822-46e4-ae64-f54d07e8cd7b': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.5 Receptor mediated endocytosis, LDL-receptor is a classic example of this process. Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 306. Figure 8.42 The endocytic pathway. 2014.', '017d18f8-e904-4371-905c-c35b23a07117': 'Alberts B, Johnson A, Lewis J, et al. Figure 17.6 Exocytosis: vesicles containing substances fuse with the plasma membrane… Adapted under Fair Use from Cell and Molecular Biology. 6th Ed. pp 299. Figure 35 A summary of the autophagic pathway. 2014.'}"
Figure 16.1,cell_bio/images/Figure 16.1.jpg,Figure 16.1: Schematic of the cell membrane. Plasma membranes range from 5 to 10 nm in thickness.,"The fluid mosaic model describes the plasma membrane structure as a mosaic of components — including phospholipids, cholesterol, proteins, and carbohydrates — that gives the membrane a fluid character. Plasma membranes range from 5 to 10 nm in thickness (figure 16.1). The protein, lipid, and carbohydrate proportions in the plasma membrane vary with cell type.","{'3f0380cf-e47f-4898-8d8d-8eb24fcacc3f': 'The fluid mosaic model describes the plasma membrane structure as a mosaic of components —\xa0including phospholipids, cholesterol, proteins, and carbohydrates —\xa0that gives the membrane a fluid character. Plasma membranes range from 5 to 10 nm in thickness (figure 16.1). The protein, lipid, and carbohydrate proportions in the plasma membrane vary with cell type.', 'e95c58bc-9740-4db8-96fd-a1ba38612c49': 'The integral proteins and lipids exist in the membrane as separate but loosely attached molecules. The membraneʼs mosaic characteristics explain some but not all of its fluidity. There are two other factors that help maintain this fluid characteristic.', '66ac4fb8-4015-45c2-a56d-7cf08e5ca809': 'One factor is the nature of the phospholipids themselves. In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms. There are no double bonds between adjacent carbon atoms. This results in tails that are relatively straight. In contrast, unsaturated fatty acids do not contain a maximal number of hydrogen atoms, but they do contain some double bonds between adjacent carbon atoms.', '306cf956-2726-4a2a-a6ec-51ebf8f9fe44': 'Temperature can also influence membrane rigidity. Decreasing temperatures compress saturated fatty acids with their straight tails, and they press in on each other, making a dense and fairly rigid membrane. If unsaturated fatty acids are compressed, the “kinks” in their tails elbow adjacent phospholipid molecules away, maintaining some space between the phospholipid molecules. This “elbow room” helps\xa0maintain fluidity in the membrane at temperatures at which membranes with saturated fatty acid tails in their phospholipids would “freeze” or solidify.', 'bad7fc51-1890-40dc-97ca-570cc46c1a67': '16.1 References and resources', '20714ecd-650e-4675-ab00-fbea5ac8287c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 4: The Structure and Function of the Plasma Membrane.', '6654f888-3e5c-441e-9b9c-9c1e9777bd93': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 49.', 'b15d658a-4218-426b-afc4-fdfaa2f1ae76': '16.2 Passive Transport', '965cce02-2bce-4a5d-a2db-e75a1eecce4e': 'Plasma membranes must allow certain substances to enter and leave a cell, and prevent some harmful materials from entering and some essential materials from leaving. In other words, plasma membranes are selectively permeable;\xa0they allow some substances to pass through, but not others. If they were to lose this selectivity, the cell would no longer be able to sustain itself, and it would be destroyed. There are four major types of transport across the cell membrane:', 'd0456482-8bd5-483f-876b-d25c4e749298': 'Recall that plasma membranes are amphiphilic: they have hydrophilic and hydrophobic regions. This characteristic helps move some materials through the membrane and hinders the movement of others.', 'd83b6775-e57b-45c0-8b7c-500d29e22081': 'Nonpolar and lipid-soluble material with a low molecular weight can easily slip through the membraneʼs hydrophobic lipid core. Substances such as the fat-soluble vitamins A, D, E, and K readily pass through the plasma membranes in the digestive tract and other tissues. Fat-soluble drugs and hormones also gain easy entry into cells and readily transport themselves into the bodyʼs tissues and organs. Oxygen and carbon dioxide molecules have no charge and pass through membranes by simple diffusion.'}"
Figure 16.2,cell_bio/images/Figure 16.2.jpg,Figure 16.2: Structure of a phospholipid.,"The membraneʼs main fabric comprises amphiphilic, phospholipid molecules. The hydrophilic or “water-loving” areas of these molecules (figure 16.2) are in contact with the aqueous fluid both inside and outside the cell. Hydrophobic or “water-hating” molecules tend to be nonpolar. They interact with other nonpolar molecules in chemical reactions, but generally do not interact with polar molecules. A phospholipid molecule consists of a three-carbon glycerol backbone with two fatty acid molecules attached. This arrangement gives the overall molecule a head area (the phosphatecontaining group), which has a polar character or negative charge, and a tail area (the fatty acids), which has no charge. The head can form hydrogen bonds, but the tail cannot (figure 16.2).","{'1aaaa479-7562-457c-862c-ee45c3078db6': 'The membraneʼs main fabric comprises amphiphilic, phospholipid molecules. The hydrophilic or “water-loving” areas of these molecules (figure 16.2) are in contact with the aqueous fluid both inside and outside the cell. Hydrophobic\xa0or “water-hating” molecules\xa0tend to be nonpolar. They interact with other nonpolar molecules in chemical reactions, but generally do not interact with polar molecules. A phospholipid molecule consists of a three-carbon glycerol backbone with two fatty acid molecules attached. This arrangement gives the overall molecule a head area (the phosphatecontaining group), which has a polar character or negative charge, and a tail area (the fatty acids), which has no charge. The head can form hydrogen bonds, but the tail cannot (figure 16.2).', 'f6bcd43e-c81e-4adf-a95e-067d460fed2d': 'Cholesterol, another lipid comprised of four fused carbon rings, is situated alongside the phospholipids in the membraneʼs core (figure 16.2).', '6ac81ef3-05dc-47f3-bcd4-821977696124': 'Specific phospholipids play key roles in the membrane; phosphatidylcholine, serine, inositol, and ethanolamine (figure 16.3) play various roles in the membrane.', 'e95c58bc-9740-4db8-96fd-a1ba38612c49': 'The integral proteins and lipids exist in the membrane as separate but loosely attached molecules. The membraneʼs mosaic characteristics explain some but not all of its fluidity. There are two other factors that help maintain this fluid characteristic.', '66ac4fb8-4015-45c2-a56d-7cf08e5ca809': 'One factor is the nature of the phospholipids themselves. In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms. There are no double bonds between adjacent carbon atoms. This results in tails that are relatively straight. In contrast, unsaturated fatty acids do not contain a maximal number of hydrogen atoms, but they do contain some double bonds between adjacent carbon atoms.', '306cf956-2726-4a2a-a6ec-51ebf8f9fe44': 'Temperature can also influence membrane rigidity. Decreasing temperatures compress saturated fatty acids with their straight tails, and they press in on each other, making a dense and fairly rigid membrane. If unsaturated fatty acids are compressed, the “kinks” in their tails elbow adjacent phospholipid molecules away, maintaining some space between the phospholipid molecules. This “elbow room” helps\xa0maintain fluidity in the membrane at temperatures at which membranes with saturated fatty acid tails in their phospholipids would “freeze” or solidify.', 'bad7fc51-1890-40dc-97ca-570cc46c1a67': '16.1 References and resources', '20714ecd-650e-4675-ab00-fbea5ac8287c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 4: The Structure and Function of the Plasma Membrane.', '6654f888-3e5c-441e-9b9c-9c1e9777bd93': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 49.', 'b15d658a-4218-426b-afc4-fdfaa2f1ae76': '16.2 Passive Transport', '965cce02-2bce-4a5d-a2db-e75a1eecce4e': 'Plasma membranes must allow certain substances to enter and leave a cell, and prevent some harmful materials from entering and some essential materials from leaving. In other words, plasma membranes are selectively permeable;\xa0they allow some substances to pass through, but not others. If they were to lose this selectivity, the cell would no longer be able to sustain itself, and it would be destroyed. There are four major types of transport across the cell membrane:', 'd0456482-8bd5-483f-876b-d25c4e749298': 'Recall that plasma membranes are amphiphilic: they have hydrophilic and hydrophobic regions. This characteristic helps move some materials through the membrane and hinders the movement of others.', 'd83b6775-e57b-45c0-8b7c-500d29e22081': 'Nonpolar and lipid-soluble material with a low molecular weight can easily slip through the membraneʼs hydrophobic lipid core. Substances such as the fat-soluble vitamins A, D, E, and K readily pass through the plasma membranes in the digestive tract and other tissues. Fat-soluble drugs and hormones also gain easy entry into cells and readily transport themselves into the bodyʼs tissues and organs. Oxygen and carbon dioxide molecules have no charge and pass through membranes by simple diffusion.'}"
Figure 16.2,cell_bio/images/Figure 16.2.jpg,Figure 16.2: Structure of a phospholipid.,"The membraneʼs main fabric comprises amphiphilic, phospholipid molecules. The hydrophilic or “water-loving” areas of these molecules (figure 16.2) are in contact with the aqueous fluid both inside and outside the cell. Hydrophobic or “water-hating” molecules tend to be nonpolar. They interact with other nonpolar molecules in chemical reactions, but generally do not interact with polar molecules. A phospholipid molecule consists of a three-carbon glycerol backbone with two fatty acid molecules attached. This arrangement gives the overall molecule a head area (the phosphatecontaining group), which has a polar character or negative charge, and a tail area (the fatty acids), which has no charge. The head can form hydrogen bonds, but the tail cannot (figure 16.2).","{'1aaaa479-7562-457c-862c-ee45c3078db6': 'The membraneʼs main fabric comprises amphiphilic, phospholipid molecules. The hydrophilic or “water-loving” areas of these molecules (figure 16.2) are in contact with the aqueous fluid both inside and outside the cell. Hydrophobic\xa0or “water-hating” molecules\xa0tend to be nonpolar. They interact with other nonpolar molecules in chemical reactions, but generally do not interact with polar molecules. A phospholipid molecule consists of a three-carbon glycerol backbone with two fatty acid molecules attached. This arrangement gives the overall molecule a head area (the phosphatecontaining group), which has a polar character or negative charge, and a tail area (the fatty acids), which has no charge. The head can form hydrogen bonds, but the tail cannot (figure 16.2).', 'f6bcd43e-c81e-4adf-a95e-067d460fed2d': 'Cholesterol, another lipid comprised of four fused carbon rings, is situated alongside the phospholipids in the membraneʼs core (figure 16.2).', '6ac81ef3-05dc-47f3-bcd4-821977696124': 'Specific phospholipids play key roles in the membrane; phosphatidylcholine, serine, inositol, and ethanolamine (figure 16.3) play various roles in the membrane.', 'e95c58bc-9740-4db8-96fd-a1ba38612c49': 'The integral proteins and lipids exist in the membrane as separate but loosely attached molecules. The membraneʼs mosaic characteristics explain some but not all of its fluidity. There are two other factors that help maintain this fluid characteristic.', '66ac4fb8-4015-45c2-a56d-7cf08e5ca809': 'One factor is the nature of the phospholipids themselves. In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms. There are no double bonds between adjacent carbon atoms. This results in tails that are relatively straight. In contrast, unsaturated fatty acids do not contain a maximal number of hydrogen atoms, but they do contain some double bonds between adjacent carbon atoms.', '306cf956-2726-4a2a-a6ec-51ebf8f9fe44': 'Temperature can also influence membrane rigidity. Decreasing temperatures compress saturated fatty acids with their straight tails, and they press in on each other, making a dense and fairly rigid membrane. If unsaturated fatty acids are compressed, the “kinks” in their tails elbow adjacent phospholipid molecules away, maintaining some space between the phospholipid molecules. This “elbow room” helps\xa0maintain fluidity in the membrane at temperatures at which membranes with saturated fatty acid tails in their phospholipids would “freeze” or solidify.', 'bad7fc51-1890-40dc-97ca-570cc46c1a67': '16.1 References and resources', '20714ecd-650e-4675-ab00-fbea5ac8287c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 4: The Structure and Function of the Plasma Membrane.', '6654f888-3e5c-441e-9b9c-9c1e9777bd93': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 49.', 'b15d658a-4218-426b-afc4-fdfaa2f1ae76': '16.2 Passive Transport', '965cce02-2bce-4a5d-a2db-e75a1eecce4e': 'Plasma membranes must allow certain substances to enter and leave a cell, and prevent some harmful materials from entering and some essential materials from leaving. In other words, plasma membranes are selectively permeable;\xa0they allow some substances to pass through, but not others. If they were to lose this selectivity, the cell would no longer be able to sustain itself, and it would be destroyed. There are four major types of transport across the cell membrane:', 'd0456482-8bd5-483f-876b-d25c4e749298': 'Recall that plasma membranes are amphiphilic: they have hydrophilic and hydrophobic regions. This characteristic helps move some materials through the membrane and hinders the movement of others.', 'd83b6775-e57b-45c0-8b7c-500d29e22081': 'Nonpolar and lipid-soluble material with a low molecular weight can easily slip through the membraneʼs hydrophobic lipid core. Substances such as the fat-soluble vitamins A, D, E, and K readily pass through the plasma membranes in the digestive tract and other tissues. Fat-soluble drugs and hormones also gain easy entry into cells and readily transport themselves into the bodyʼs tissues and organs. Oxygen and carbon dioxide molecules have no charge and pass through membranes by simple diffusion.'}"
Figure 16.3,cell_bio/images/Figure 16.3.jpg,Figure 16.3: Important membrane lipids.,"Specific phospholipids play key roles in the membrane; phosphatidylcholine, serine, inositol, and ethanolamine (figure 16.3) play various roles in the membrane.","{'f6bcd43e-c81e-4adf-a95e-067d460fed2d': 'Cholesterol, another lipid comprised of four fused carbon rings, is situated alongside the phospholipids in the membraneʼs core (figure 16.2).', '6ac81ef3-05dc-47f3-bcd4-821977696124': 'Specific phospholipids play key roles in the membrane; phosphatidylcholine, serine, inositol, and ethanolamine (figure 16.3) play various roles in the membrane.', 'e95c58bc-9740-4db8-96fd-a1ba38612c49': 'The integral proteins and lipids exist in the membrane as separate but loosely attached molecules. The membraneʼs mosaic characteristics explain some but not all of its fluidity. There are two other factors that help maintain this fluid characteristic.', '66ac4fb8-4015-45c2-a56d-7cf08e5ca809': 'One factor is the nature of the phospholipids themselves. In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms. There are no double bonds between adjacent carbon atoms. This results in tails that are relatively straight. In contrast, unsaturated fatty acids do not contain a maximal number of hydrogen atoms, but they do contain some double bonds between adjacent carbon atoms.', '306cf956-2726-4a2a-a6ec-51ebf8f9fe44': 'Temperature can also influence membrane rigidity. Decreasing temperatures compress saturated fatty acids with their straight tails, and they press in on each other, making a dense and fairly rigid membrane. If unsaturated fatty acids are compressed, the “kinks” in their tails elbow adjacent phospholipid molecules away, maintaining some space between the phospholipid molecules. This “elbow room” helps\xa0maintain fluidity in the membrane at temperatures at which membranes with saturated fatty acid tails in their phospholipids would “freeze” or solidify.', 'bad7fc51-1890-40dc-97ca-570cc46c1a67': '16.1 References and resources', '20714ecd-650e-4675-ab00-fbea5ac8287c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 4: The Structure and Function of the Plasma Membrane.', '6654f888-3e5c-441e-9b9c-9c1e9777bd93': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 49.', 'b15d658a-4218-426b-afc4-fdfaa2f1ae76': '16.2 Passive Transport', '965cce02-2bce-4a5d-a2db-e75a1eecce4e': 'Plasma membranes must allow certain substances to enter and leave a cell, and prevent some harmful materials from entering and some essential materials from leaving. In other words, plasma membranes are selectively permeable;\xa0they allow some substances to pass through, but not others. If they were to lose this selectivity, the cell would no longer be able to sustain itself, and it would be destroyed. There are four major types of transport across the cell membrane:', 'd0456482-8bd5-483f-876b-d25c4e749298': 'Recall that plasma membranes are amphiphilic: they have hydrophilic and hydrophobic regions. This characteristic helps move some materials through the membrane and hinders the movement of others.', 'd83b6775-e57b-45c0-8b7c-500d29e22081': 'Nonpolar and lipid-soluble material with a low molecular weight can easily slip through the membraneʼs hydrophobic lipid core. Substances such as the fat-soluble vitamins A, D, E, and K readily pass through the plasma membranes in the digestive tract and other tissues. Fat-soluble drugs and hormones also gain easy entry into cells and readily transport themselves into the bodyʼs tissues and organs. Oxygen and carbon dioxide molecules have no charge and pass through membranes by simple diffusion.'}"
Figure 16.1,cell_bio/images/Figure 16.1.jpg,Figure 16.1: Schematic of the cell membrane. Plasma membranes range from 5 to 10 nm in thickness.,"The fluid mosaic model describes the plasma membrane structure as a mosaic of components — including phospholipids, cholesterol, proteins, and carbohydrates — that gives the membrane a fluid character. Plasma membranes range from 5 to 10 nm in thickness (figure 16.1). The protein, lipid, and carbohydrate proportions in the plasma membrane vary with cell type.","{'3f0380cf-e47f-4898-8d8d-8eb24fcacc3f': 'The fluid mosaic model describes the plasma membrane structure as a mosaic of components —\xa0including phospholipids, cholesterol, proteins, and carbohydrates —\xa0that gives the membrane a fluid character. Plasma membranes range from 5 to 10 nm in thickness (figure 16.1). The protein, lipid, and carbohydrate proportions in the plasma membrane vary with cell type.', 'e95c58bc-9740-4db8-96fd-a1ba38612c49': 'The integral proteins and lipids exist in the membrane as separate but loosely attached molecules. The membraneʼs mosaic characteristics explain some but not all of its fluidity. There are two other factors that help maintain this fluid characteristic.', '66ac4fb8-4015-45c2-a56d-7cf08e5ca809': 'One factor is the nature of the phospholipids themselves. In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms. There are no double bonds between adjacent carbon atoms. This results in tails that are relatively straight. In contrast, unsaturated fatty acids do not contain a maximal number of hydrogen atoms, but they do contain some double bonds between adjacent carbon atoms.', '306cf956-2726-4a2a-a6ec-51ebf8f9fe44': 'Temperature can also influence membrane rigidity. Decreasing temperatures compress saturated fatty acids with their straight tails, and they press in on each other, making a dense and fairly rigid membrane. If unsaturated fatty acids are compressed, the “kinks” in their tails elbow adjacent phospholipid molecules away, maintaining some space between the phospholipid molecules. This “elbow room” helps\xa0maintain fluidity in the membrane at temperatures at which membranes with saturated fatty acid tails in their phospholipids would “freeze” or solidify.', 'bad7fc51-1890-40dc-97ca-570cc46c1a67': '16.1 References and resources', '20714ecd-650e-4675-ab00-fbea5ac8287c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 4: The Structure and Function of the Plasma Membrane.', '6654f888-3e5c-441e-9b9c-9c1e9777bd93': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 49.', 'b15d658a-4218-426b-afc4-fdfaa2f1ae76': '16.2 Passive Transport', '965cce02-2bce-4a5d-a2db-e75a1eecce4e': 'Plasma membranes must allow certain substances to enter and leave a cell, and prevent some harmful materials from entering and some essential materials from leaving. In other words, plasma membranes are selectively permeable;\xa0they allow some substances to pass through, but not others. If they were to lose this selectivity, the cell would no longer be able to sustain itself, and it would be destroyed. There are four major types of transport across the cell membrane:', 'd0456482-8bd5-483f-876b-d25c4e749298': 'Recall that plasma membranes are amphiphilic: they have hydrophilic and hydrophobic regions. This characteristic helps move some materials through the membrane and hinders the movement of others.', 'd83b6775-e57b-45c0-8b7c-500d29e22081': 'Nonpolar and lipid-soluble material with a low molecular weight can easily slip through the membraneʼs hydrophobic lipid core. Substances such as the fat-soluble vitamins A, D, E, and K readily pass through the plasma membranes in the digestive tract and other tissues. Fat-soluble drugs and hormones also gain easy entry into cells and readily transport themselves into the bodyʼs tissues and organs. Oxygen and carbon dioxide molecules have no charge and pass through membranes by simple diffusion.'}"
Figure 16.2,cell_bio/images/Figure 16.2.jpg,Figure 16.2: Structure of a phospholipid.,"The membraneʼs main fabric comprises amphiphilic, phospholipid molecules. The hydrophilic or “water-loving” areas of these molecules (figure 16.2) are in contact with the aqueous fluid both inside and outside the cell. Hydrophobic or “water-hating” molecules tend to be nonpolar. They interact with other nonpolar molecules in chemical reactions, but generally do not interact with polar molecules. A phospholipid molecule consists of a three-carbon glycerol backbone with two fatty acid molecules attached. This arrangement gives the overall molecule a head area (the phosphatecontaining group), which has a polar character or negative charge, and a tail area (the fatty acids), which has no charge. The head can form hydrogen bonds, but the tail cannot (figure 16.2).","{'1aaaa479-7562-457c-862c-ee45c3078db6': 'The membraneʼs main fabric comprises amphiphilic, phospholipid molecules. The hydrophilic or “water-loving” areas of these molecules (figure 16.2) are in contact with the aqueous fluid both inside and outside the cell. Hydrophobic\xa0or “water-hating” molecules\xa0tend to be nonpolar. They interact with other nonpolar molecules in chemical reactions, but generally do not interact with polar molecules. A phospholipid molecule consists of a three-carbon glycerol backbone with two fatty acid molecules attached. This arrangement gives the overall molecule a head area (the phosphatecontaining group), which has a polar character or negative charge, and a tail area (the fatty acids), which has no charge. The head can form hydrogen bonds, but the tail cannot (figure 16.2).', 'f6bcd43e-c81e-4adf-a95e-067d460fed2d': 'Cholesterol, another lipid comprised of four fused carbon rings, is situated alongside the phospholipids in the membraneʼs core (figure 16.2).', '6ac81ef3-05dc-47f3-bcd4-821977696124': 'Specific phospholipids play key roles in the membrane; phosphatidylcholine, serine, inositol, and ethanolamine (figure 16.3) play various roles in the membrane.', 'e95c58bc-9740-4db8-96fd-a1ba38612c49': 'The integral proteins and lipids exist in the membrane as separate but loosely attached molecules. The membraneʼs mosaic characteristics explain some but not all of its fluidity. There are two other factors that help maintain this fluid characteristic.', '66ac4fb8-4015-45c2-a56d-7cf08e5ca809': 'One factor is the nature of the phospholipids themselves. In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms. There are no double bonds between adjacent carbon atoms. This results in tails that are relatively straight. In contrast, unsaturated fatty acids do not contain a maximal number of hydrogen atoms, but they do contain some double bonds between adjacent carbon atoms.', '306cf956-2726-4a2a-a6ec-51ebf8f9fe44': 'Temperature can also influence membrane rigidity. Decreasing temperatures compress saturated fatty acids with their straight tails, and they press in on each other, making a dense and fairly rigid membrane. If unsaturated fatty acids are compressed, the “kinks” in their tails elbow adjacent phospholipid molecules away, maintaining some space between the phospholipid molecules. This “elbow room” helps\xa0maintain fluidity in the membrane at temperatures at which membranes with saturated fatty acid tails in their phospholipids would “freeze” or solidify.', 'bad7fc51-1890-40dc-97ca-570cc46c1a67': '16.1 References and resources', '20714ecd-650e-4675-ab00-fbea5ac8287c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 4: The Structure and Function of the Plasma Membrane.', '6654f888-3e5c-441e-9b9c-9c1e9777bd93': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 49.', 'b15d658a-4218-426b-afc4-fdfaa2f1ae76': '16.2 Passive Transport', '965cce02-2bce-4a5d-a2db-e75a1eecce4e': 'Plasma membranes must allow certain substances to enter and leave a cell, and prevent some harmful materials from entering and some essential materials from leaving. In other words, plasma membranes are selectively permeable;\xa0they allow some substances to pass through, but not others. If they were to lose this selectivity, the cell would no longer be able to sustain itself, and it would be destroyed. There are four major types of transport across the cell membrane:', 'd0456482-8bd5-483f-876b-d25c4e749298': 'Recall that plasma membranes are amphiphilic: they have hydrophilic and hydrophobic regions. This characteristic helps move some materials through the membrane and hinders the movement of others.', 'd83b6775-e57b-45c0-8b7c-500d29e22081': 'Nonpolar and lipid-soluble material with a low molecular weight can easily slip through the membraneʼs hydrophobic lipid core. Substances such as the fat-soluble vitamins A, D, E, and K readily pass through the plasma membranes in the digestive tract and other tissues. Fat-soluble drugs and hormones also gain easy entry into cells and readily transport themselves into the bodyʼs tissues and organs. Oxygen and carbon dioxide molecules have no charge and pass through membranes by simple diffusion.'}"
Figure 16.3,cell_bio/images/Figure 16.3.jpg,Figure 16.3: Important membrane lipids.,"Specific phospholipids play key roles in the membrane; phosphatidylcholine, serine, inositol, and ethanolamine (figure 16.3) play various roles in the membrane.","{'f6bcd43e-c81e-4adf-a95e-067d460fed2d': 'Cholesterol, another lipid comprised of four fused carbon rings, is situated alongside the phospholipids in the membraneʼs core (figure 16.2).', '6ac81ef3-05dc-47f3-bcd4-821977696124': 'Specific phospholipids play key roles in the membrane; phosphatidylcholine, serine, inositol, and ethanolamine (figure 16.3) play various roles in the membrane.', 'e95c58bc-9740-4db8-96fd-a1ba38612c49': 'The integral proteins and lipids exist in the membrane as separate but loosely attached molecules. The membraneʼs mosaic characteristics explain some but not all of its fluidity. There are two other factors that help maintain this fluid characteristic.', '66ac4fb8-4015-45c2-a56d-7cf08e5ca809': 'One factor is the nature of the phospholipids themselves. In their saturated form, the fatty acids in phospholipid tails are saturated with bound hydrogen atoms. There are no double bonds between adjacent carbon atoms. This results in tails that are relatively straight. In contrast, unsaturated fatty acids do not contain a maximal number of hydrogen atoms, but they do contain some double bonds between adjacent carbon atoms.', '306cf956-2726-4a2a-a6ec-51ebf8f9fe44': 'Temperature can also influence membrane rigidity. Decreasing temperatures compress saturated fatty acids with their straight tails, and they press in on each other, making a dense and fairly rigid membrane. If unsaturated fatty acids are compressed, the “kinks” in their tails elbow adjacent phospholipid molecules away, maintaining some space between the phospholipid molecules. This “elbow room” helps\xa0maintain fluidity in the membrane at temperatures at which membranes with saturated fatty acid tails in their phospholipids would “freeze” or solidify.', 'bad7fc51-1890-40dc-97ca-570cc46c1a67': '16.1 References and resources', '20714ecd-650e-4675-ab00-fbea5ac8287c': 'Karp, G., and J. G. Patton.\xa0Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 4: The Structure and Function of the Plasma Membrane.', '6654f888-3e5c-441e-9b9c-9c1e9777bd93': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 49.', 'b15d658a-4218-426b-afc4-fdfaa2f1ae76': '16.2 Passive Transport', '965cce02-2bce-4a5d-a2db-e75a1eecce4e': 'Plasma membranes must allow certain substances to enter and leave a cell, and prevent some harmful materials from entering and some essential materials from leaving. In other words, plasma membranes are selectively permeable;\xa0they allow some substances to pass through, but not others. If they were to lose this selectivity, the cell would no longer be able to sustain itself, and it would be destroyed. There are four major types of transport across the cell membrane:', 'd0456482-8bd5-483f-876b-d25c4e749298': 'Recall that plasma membranes are amphiphilic: they have hydrophilic and hydrophobic regions. This characteristic helps move some materials through the membrane and hinders the movement of others.', 'd83b6775-e57b-45c0-8b7c-500d29e22081': 'Nonpolar and lipid-soluble material with a low molecular weight can easily slip through the membraneʼs hydrophobic lipid core. Substances such as the fat-soluble vitamins A, D, E, and K readily pass through the plasma membranes in the digestive tract and other tissues. Fat-soluble drugs and hormones also gain easy entry into cells and readily transport themselves into the bodyʼs tissues and organs. Oxygen and carbon dioxide molecules have no charge and pass through membranes by simple diffusion.'}"
Figure 16.4,cell_bio/images/Figure 16.4.jpg,Figure 16.4: Diffusion across the plasma membrane.,"Diffusion is a passive process of transport. A single substance moves from a high concentration to a low concentration area until the concentration is equal across a space (figure 16.4). Materials move within the cellʼs cytosol by diffusion, and certain materials move through the plasma membrane by diffusion such as lipids and fat-soluble vitamins. Diffusion expends no energy. On the contrary, concentration gradients are a form of potential energy, which dissipates as the gradient is eliminated.","{'550b5322-064f-4663-85ac-508ce5d2973f': 'Diffusion is a passive process of transport. A single substance moves from a high concentration to a low concentration area until the concentration is equal across a space (figure 16.4). Materials move within the cellʼs cytosol by diffusion, and certain materials move through the plasma membrane by diffusion such as lipids and fat-soluble vitamins. Diffusion expends no energy. On the contrary, concentration gradients are a form of potential energy, which dissipates as the gradient is eliminated.', 'd4dd56cb-80ff-40e9-bc71-702cd7070e76': 'Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, thus triggers a change of its own shape, moving the bound molecule from the cellʼs outside to its interior (figure 16.8).', '4bc1a57f-2fd7-4991-8c3d-5067ece820b7': 'Depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This selectivity adds to the plasma membraneʼs overall selectivity. One group of carrier proteins, glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.', 'b3861f4b-743e-45f6-82f3-01cec421df8d': 'Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second,\xa0whereas\xa0carrier proteins work at a rate of a thousand to a million molecules per second.', 'c1a691d9-5eca-4329-bd04-ce256f63fd1d': '16.2 References and resources', '4488bf3b-b43a-4b89-8a17-3cb1d8daf6bc': 'Lieberman M, Peet A. Figure 16.7 Protein channel. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '9dd753d9-f995-4b3b-b975-5931a92a5c6b': 'Lieberman M, Peet A. Figure 16.8 Carrier proteins… Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', 'e37885a6-dda6-4a4d-93b9-a16ec574d053': '16.3 Active Transport', '43b5c5a7-5f74-43f1-adbb-3e6ccd388a50': 'Active transport mechanisms require the cellʼs energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient —\xa0that is, if the substanceʼs concentration inside the cell is greater than its concentration in the extracellular fluid (and vice versa) —\xa0the cell must use energy to move the substance.'}"
Figure 16.5,cell_bio/images/Figure 16.5.jpg,"Figure 16.5: Illustration of osmosis. In the diagram, the solute cannot pass through the selectively permeable membrane, but the water can.","Osmosis is the movement of water through a semipermeable membrane according to the waterʼs concentration gradient across the membrane, which is inversely proportional to the solute’s concentration. While diffusion transports material across membranes and within cells, osmosis transports only water across a membrane, and the membrane limits the solute’s diffusion in the water (figure 16.5). Not surprisingly, the aquaporins that facilitate water movement play a large role in osmosis, most prominently in red blood cells and the membranes of kidney tubules. In osmosis, water always moves from an area of higher water concentration to one of lower concentration.","{'ce084e63-75ad-44d1-a3c2-d458cdc0faf7': 'Osmosis is the movement of water through a semipermeable membrane according to the waterʼs concentration gradient across the membrane, which is inversely proportional to the solute’s\xa0concentration. While diffusion transports material across membranes and within cells, osmosis transports only water across a membrane, and the membrane limits the solute’s\xa0diffusion in the water (figure 16.5). Not surprisingly, the aquaporins that facilitate water movement play a large role in osmosis, most prominently in red blood cells and the membranes of kidney tubules. In osmosis, water always moves from an area of higher water concentration to one of lower concentration.', 'd4dd56cb-80ff-40e9-bc71-702cd7070e76': 'Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, thus triggers a change of its own shape, moving the bound molecule from the cellʼs outside to its interior (figure 16.8).', '4bc1a57f-2fd7-4991-8c3d-5067ece820b7': 'Depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This selectivity adds to the plasma membraneʼs overall selectivity. One group of carrier proteins, glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.', 'b3861f4b-743e-45f6-82f3-01cec421df8d': 'Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second,\xa0whereas\xa0carrier proteins work at a rate of a thousand to a million molecules per second.', 'c1a691d9-5eca-4329-bd04-ce256f63fd1d': '16.2 References and resources', '4488bf3b-b43a-4b89-8a17-3cb1d8daf6bc': 'Lieberman M, Peet A. Figure 16.7 Protein channel. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '9dd753d9-f995-4b3b-b975-5931a92a5c6b': 'Lieberman M, Peet A. Figure 16.8 Carrier proteins… Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', 'e37885a6-dda6-4a4d-93b9-a16ec574d053': '16.3 Active Transport', '43b5c5a7-5f74-43f1-adbb-3e6ccd388a50': 'Active transport mechanisms require the cellʼs energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient —\xa0that is, if the substanceʼs concentration inside the cell is greater than its concentration in the extracellular fluid (and vice versa) —\xa0the cell must use energy to move the substance.'}"
Figure 16.6,cell_bio/images/Figure 16.6.jpg,"Figure 16.6: Comparison of red blood cell morphology in isotonic, hypertonic, and hypotonic solutions.","In an isotonic solution, the extracellular fluid has the same osmolarity as the cell. If the cellʼs osmolarity matches that of the extracellular fluid, there will be no net movement of water into or out of the cell, although water will still move in and out. Osmotic pressure changes red blood cellsʼ shape in hypertonic, isotonic, and hypotonic solutions (figure 16.6).","{'17b21802-7f8e-4717-ab97-8368080a8d50': 'In an isotonic solution, the extracellular fluid has the same osmolarity as the cell. If the cellʼs osmolarity matches that of the extracellular fluid, there will be no net movement of water into or out of the cell, although water will still move in and out. Osmotic pressure changes red blood cellsʼ shape in hypertonic, isotonic, and hypotonic solutions (figure 16.6).', 'd4dd56cb-80ff-40e9-bc71-702cd7070e76': 'Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, thus triggers a change of its own shape, moving the bound molecule from the cellʼs outside to its interior (figure 16.8).', '4bc1a57f-2fd7-4991-8c3d-5067ece820b7': 'Depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This selectivity adds to the plasma membraneʼs overall selectivity. One group of carrier proteins, glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.', 'b3861f4b-743e-45f6-82f3-01cec421df8d': 'Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second,\xa0whereas\xa0carrier proteins work at a rate of a thousand to a million molecules per second.', 'c1a691d9-5eca-4329-bd04-ce256f63fd1d': '16.2 References and resources', '4488bf3b-b43a-4b89-8a17-3cb1d8daf6bc': 'Lieberman M, Peet A. Figure 16.7 Protein channel. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '9dd753d9-f995-4b3b-b975-5931a92a5c6b': 'Lieberman M, Peet A. Figure 16.8 Carrier proteins… Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', 'e37885a6-dda6-4a4d-93b9-a16ec574d053': '16.3 Active Transport', '43b5c5a7-5f74-43f1-adbb-3e6ccd388a50': 'Active transport mechanisms require the cellʼs energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient —\xa0that is, if the substanceʼs concentration inside the cell is greater than its concentration in the extracellular fluid (and vice versa) —\xa0the cell must use energy to move the substance.'}"
Figure 16.7,cell_bio/images/Figure 16.7.jpg,Figure 16.7: Protein channel.,"Channels are specific for the transported substance. Channel proteins have hydrophilic domains exposed to the intracellular and extracellular fluids. In addition, they have a hydrophilic channel through their core that provides a hydrated opening through the membrane layers (figure 16.7).","{'02363e2c-0819-4eb4-b6ee-da074c4f3551': 'Channels are specific for the transported substance. Channel proteins have hydrophilic domains exposed to the intracellular and extracellular fluids. In addition, they have a hydrophilic channel through their core that provides a hydrated opening through the membrane layers (figure 16.7).', '91a46208-db56-4a32-b18e-380a6f726afe': 'Channel proteins are either open at all times or they are “gated,” which controls the channelʼs opening. The gating can be controlled by volatage, ligand (such as ATP), or mechanical stimulus. When a particular ion attaches to the channel protein, it may control the opening, or other mechanisms or substances may be involved.', '8f80ee92-5e64-4024-8e2d-a38b2339e1fe': 'In some tissues, sodium and chloride ions pass freely through open channels,\xa0whereas\xa0in other tissues a gate must open to allow passage. Cells involved in transmitting electrical impulses, such as nerve and muscle cells, have gated channels for sodium, potassium, and calcium in their membranes. Opening and closing these channels changes the relative concentrations on opposing sides of the membrane of these ions, resulting in facilitating electrical transmission along membranes (in the case of nerve cells) or in muscle contraction (in the case of muscle cells).', 'd4dd56cb-80ff-40e9-bc71-702cd7070e76': 'Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, thus triggers a change of its own shape, moving the bound molecule from the cellʼs outside to its interior (figure 16.8).', '4bc1a57f-2fd7-4991-8c3d-5067ece820b7': 'Depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This selectivity adds to the plasma membraneʼs overall selectivity. One group of carrier proteins, glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.', 'b3861f4b-743e-45f6-82f3-01cec421df8d': 'Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second,\xa0whereas\xa0carrier proteins work at a rate of a thousand to a million molecules per second.', 'c1a691d9-5eca-4329-bd04-ce256f63fd1d': '16.2 References and resources', '4488bf3b-b43a-4b89-8a17-3cb1d8daf6bc': 'Lieberman M, Peet A. Figure 16.7 Protein channel. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '9dd753d9-f995-4b3b-b975-5931a92a5c6b': 'Lieberman M, Peet A. Figure 16.8 Carrier proteins… Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', 'e37885a6-dda6-4a4d-93b9-a16ec574d053': '16.3 Active Transport', '43b5c5a7-5f74-43f1-adbb-3e6ccd388a50': 'Active transport mechanisms require the cellʼs energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient —\xa0that is, if the substanceʼs concentration inside the cell is greater than its concentration in the extracellular fluid (and vice versa) —\xa0the cell must use energy to move the substance.'}"
Figure 16.8,cell_bio/images/Figure 16.8.jpg,"Figure 16.8: Carrier proteins. This aptly named protein binds a substance and thus triggers a change of its own shape, moving the bound molecule from the cell’s outside to its interior.","Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, thus triggers a change of its own shape, moving the bound molecule from the cellʼs outside to its interior (figure 16.8).","{'d4dd56cb-80ff-40e9-bc71-702cd7070e76': 'Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, thus triggers a change of its own shape, moving the bound molecule from the cellʼs outside to its interior (figure 16.8).', '4bc1a57f-2fd7-4991-8c3d-5067ece820b7': 'Depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This selectivity adds to the plasma membraneʼs overall selectivity. One group of carrier proteins, glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.', 'b3861f4b-743e-45f6-82f3-01cec421df8d': 'Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second,\xa0whereas\xa0carrier proteins work at a rate of a thousand to a million molecules per second.', 'c1a691d9-5eca-4329-bd04-ce256f63fd1d': '16.2 References and resources', '4488bf3b-b43a-4b89-8a17-3cb1d8daf6bc': 'Lieberman M, Peet A. Figure 16.7 Protein channel. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '9dd753d9-f995-4b3b-b975-5931a92a5c6b': 'Lieberman M, Peet A. Figure 16.8 Carrier proteins… Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', 'e37885a6-dda6-4a4d-93b9-a16ec574d053': '16.3 Active Transport', '43b5c5a7-5f74-43f1-adbb-3e6ccd388a50': 'Active transport mechanisms require the cellʼs energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient —\xa0that is, if the substanceʼs concentration inside the cell is greater than its concentration in the extracellular fluid (and vice versa) —\xa0the cell must use energy to move the substance.'}"
Figure 16.4,cell_bio/images/Figure 16.4.jpg,Figure 16.4: Diffusion across the plasma membrane.,"Diffusion is a passive process of transport. A single substance moves from a high concentration to a low concentration area until the concentration is equal across a space (figure 16.4). Materials move within the cellʼs cytosol by diffusion, and certain materials move through the plasma membrane by diffusion such as lipids and fat-soluble vitamins. Diffusion expends no energy. On the contrary, concentration gradients are a form of potential energy, which dissipates as the gradient is eliminated.","{'550b5322-064f-4663-85ac-508ce5d2973f': 'Diffusion is a passive process of transport. A single substance moves from a high concentration to a low concentration area until the concentration is equal across a space (figure 16.4). Materials move within the cellʼs cytosol by diffusion, and certain materials move through the plasma membrane by diffusion such as lipids and fat-soluble vitamins. Diffusion expends no energy. On the contrary, concentration gradients are a form of potential energy, which dissipates as the gradient is eliminated.', 'd4dd56cb-80ff-40e9-bc71-702cd7070e76': 'Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, thus triggers a change of its own shape, moving the bound molecule from the cellʼs outside to its interior (figure 16.8).', '4bc1a57f-2fd7-4991-8c3d-5067ece820b7': 'Depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This selectivity adds to the plasma membraneʼs overall selectivity. One group of carrier proteins, glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.', 'b3861f4b-743e-45f6-82f3-01cec421df8d': 'Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second,\xa0whereas\xa0carrier proteins work at a rate of a thousand to a million molecules per second.', 'c1a691d9-5eca-4329-bd04-ce256f63fd1d': '16.2 References and resources', '4488bf3b-b43a-4b89-8a17-3cb1d8daf6bc': 'Lieberman M, Peet A. Figure 16.7 Protein channel. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '9dd753d9-f995-4b3b-b975-5931a92a5c6b': 'Lieberman M, Peet A. Figure 16.8 Carrier proteins… Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', 'e37885a6-dda6-4a4d-93b9-a16ec574d053': '16.3 Active Transport', '43b5c5a7-5f74-43f1-adbb-3e6ccd388a50': 'Active transport mechanisms require the cellʼs energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient —\xa0that is, if the substanceʼs concentration inside the cell is greater than its concentration in the extracellular fluid (and vice versa) —\xa0the cell must use energy to move the substance.'}"
Figure 16.5,cell_bio/images/Figure 16.5.jpg,"Figure 16.5: Illustration of osmosis. In the diagram, the solute cannot pass through the selectively permeable membrane, but the water can.","Osmosis is the movement of water through a semipermeable membrane according to the waterʼs concentration gradient across the membrane, which is inversely proportional to the solute’s concentration. While diffusion transports material across membranes and within cells, osmosis transports only water across a membrane, and the membrane limits the solute’s diffusion in the water (figure 16.5). Not surprisingly, the aquaporins that facilitate water movement play a large role in osmosis, most prominently in red blood cells and the membranes of kidney tubules. In osmosis, water always moves from an area of higher water concentration to one of lower concentration.","{'ce084e63-75ad-44d1-a3c2-d458cdc0faf7': 'Osmosis is the movement of water through a semipermeable membrane according to the waterʼs concentration gradient across the membrane, which is inversely proportional to the solute’s\xa0concentration. While diffusion transports material across membranes and within cells, osmosis transports only water across a membrane, and the membrane limits the solute’s\xa0diffusion in the water (figure 16.5). Not surprisingly, the aquaporins that facilitate water movement play a large role in osmosis, most prominently in red blood cells and the membranes of kidney tubules. In osmosis, water always moves from an area of higher water concentration to one of lower concentration.', 'd4dd56cb-80ff-40e9-bc71-702cd7070e76': 'Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, thus triggers a change of its own shape, moving the bound molecule from the cellʼs outside to its interior (figure 16.8).', '4bc1a57f-2fd7-4991-8c3d-5067ece820b7': 'Depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This selectivity adds to the plasma membraneʼs overall selectivity. One group of carrier proteins, glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.', 'b3861f4b-743e-45f6-82f3-01cec421df8d': 'Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second,\xa0whereas\xa0carrier proteins work at a rate of a thousand to a million molecules per second.', 'c1a691d9-5eca-4329-bd04-ce256f63fd1d': '16.2 References and resources', '4488bf3b-b43a-4b89-8a17-3cb1d8daf6bc': 'Lieberman M, Peet A. Figure 16.7 Protein channel. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '9dd753d9-f995-4b3b-b975-5931a92a5c6b': 'Lieberman M, Peet A. Figure 16.8 Carrier proteins… Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', 'e37885a6-dda6-4a4d-93b9-a16ec574d053': '16.3 Active Transport', '43b5c5a7-5f74-43f1-adbb-3e6ccd388a50': 'Active transport mechanisms require the cellʼs energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient —\xa0that is, if the substanceʼs concentration inside the cell is greater than its concentration in the extracellular fluid (and vice versa) —\xa0the cell must use energy to move the substance.'}"
Figure 16.6,cell_bio/images/Figure 16.6.jpg,"Figure 16.6: Comparison of red blood cell morphology in isotonic, hypertonic, and hypotonic solutions.","In an isotonic solution, the extracellular fluid has the same osmolarity as the cell. If the cellʼs osmolarity matches that of the extracellular fluid, there will be no net movement of water into or out of the cell, although water will still move in and out. Osmotic pressure changes red blood cellsʼ shape in hypertonic, isotonic, and hypotonic solutions (figure 16.6).","{'17b21802-7f8e-4717-ab97-8368080a8d50': 'In an isotonic solution, the extracellular fluid has the same osmolarity as the cell. If the cellʼs osmolarity matches that of the extracellular fluid, there will be no net movement of water into or out of the cell, although water will still move in and out. Osmotic pressure changes red blood cellsʼ shape in hypertonic, isotonic, and hypotonic solutions (figure 16.6).', 'd4dd56cb-80ff-40e9-bc71-702cd7070e76': 'Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, thus triggers a change of its own shape, moving the bound molecule from the cellʼs outside to its interior (figure 16.8).', '4bc1a57f-2fd7-4991-8c3d-5067ece820b7': 'Depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This selectivity adds to the plasma membraneʼs overall selectivity. One group of carrier proteins, glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.', 'b3861f4b-743e-45f6-82f3-01cec421df8d': 'Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second,\xa0whereas\xa0carrier proteins work at a rate of a thousand to a million molecules per second.', 'c1a691d9-5eca-4329-bd04-ce256f63fd1d': '16.2 References and resources', '4488bf3b-b43a-4b89-8a17-3cb1d8daf6bc': 'Lieberman M, Peet A. Figure 16.7 Protein channel. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '9dd753d9-f995-4b3b-b975-5931a92a5c6b': 'Lieberman M, Peet A. Figure 16.8 Carrier proteins… Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', 'e37885a6-dda6-4a4d-93b9-a16ec574d053': '16.3 Active Transport', '43b5c5a7-5f74-43f1-adbb-3e6ccd388a50': 'Active transport mechanisms require the cellʼs energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient —\xa0that is, if the substanceʼs concentration inside the cell is greater than its concentration in the extracellular fluid (and vice versa) —\xa0the cell must use energy to move the substance.'}"
Figure 16.7,cell_bio/images/Figure 16.7.jpg,Figure 16.7: Protein channel.,"Channels are specific for the transported substance. Channel proteins have hydrophilic domains exposed to the intracellular and extracellular fluids. In addition, they have a hydrophilic channel through their core that provides a hydrated opening through the membrane layers (figure 16.7).","{'02363e2c-0819-4eb4-b6ee-da074c4f3551': 'Channels are specific for the transported substance. Channel proteins have hydrophilic domains exposed to the intracellular and extracellular fluids. In addition, they have a hydrophilic channel through their core that provides a hydrated opening through the membrane layers (figure 16.7).', '91a46208-db56-4a32-b18e-380a6f726afe': 'Channel proteins are either open at all times or they are “gated,” which controls the channelʼs opening. The gating can be controlled by volatage, ligand (such as ATP), or mechanical stimulus. When a particular ion attaches to the channel protein, it may control the opening, or other mechanisms or substances may be involved.', '8f80ee92-5e64-4024-8e2d-a38b2339e1fe': 'In some tissues, sodium and chloride ions pass freely through open channels,\xa0whereas\xa0in other tissues a gate must open to allow passage. Cells involved in transmitting electrical impulses, such as nerve and muscle cells, have gated channels for sodium, potassium, and calcium in their membranes. Opening and closing these channels changes the relative concentrations on opposing sides of the membrane of these ions, resulting in facilitating electrical transmission along membranes (in the case of nerve cells) or in muscle contraction (in the case of muscle cells).', 'd4dd56cb-80ff-40e9-bc71-702cd7070e76': 'Another type of protein embedded in the plasma membrane is a carrier protein. This aptly named protein binds a substance and, thus triggers a change of its own shape, moving the bound molecule from the cellʼs outside to its interior (figure 16.8).', '4bc1a57f-2fd7-4991-8c3d-5067ece820b7': 'Depending on the gradient, the material may move in the opposite direction. Carrier proteins are typically specific for a single substance. This selectivity adds to the plasma membraneʼs overall selectivity. One group of carrier proteins, glucose transport proteins, or GLUTs, are involved in transporting glucose and other hexose sugars through plasma membranes within the body.', 'b3861f4b-743e-45f6-82f3-01cec421df8d': 'Channel and carrier proteins transport material at different rates. Channel proteins transport much more quickly than carrier proteins. Channel proteins facilitate diffusion at a rate of tens of millions of molecules per second,\xa0whereas\xa0carrier proteins work at a rate of a thousand to a million molecules per second.', 'c1a691d9-5eca-4329-bd04-ce256f63fd1d': '16.2 References and resources', '4488bf3b-b43a-4b89-8a17-3cb1d8daf6bc': 'Lieberman M, Peet A. Figure 16.7 Protein channel. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '9dd753d9-f995-4b3b-b975-5931a92a5c6b': 'Lieberman M, Peet A. Figure 16.8 Carrier proteins… Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.7 Common types of transport mechanisms for human cells. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', 'e37885a6-dda6-4a4d-93b9-a16ec574d053': '16.3 Active Transport', '43b5c5a7-5f74-43f1-adbb-3e6ccd388a50': 'Active transport mechanisms require the cellʼs energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient —\xa0that is, if the substanceʼs concentration inside the cell is greater than its concentration in the extracellular fluid (and vice versa) —\xa0the cell must use energy to move the substance.'}"
Figure 16.9,cell_bio/images/Figure 16.9.jpg,Figure 16.9: Electrochemical gradients.,"The interior of living cells is electrically negative with respect to the extracellular fluid in which they are bathed, and at the same time, cells have higher concentrations of potassium (K+) and lower concentrations of sodium (Na+) than the extracellular fluid. Thus in a living cell, the concentration gradient of Na+ tends to drive it into the cell, and its electrical gradient (a positive ion) also drives it inward to the negatively charged interior. However, the situation is more complex for other elements such as potassium. The electrical gradient of K+, a positive ion, also drives it into the cell, but the concentration gradient of K+ drives K+ out of the cell (figure 16.9). We call the combined concentration gradient and electrical charge that affects an ion its electrochemical gradient.","{'592203af-40f2-4feb-9c5d-549ae9bc410a': 'We have discussed simple concentration gradients —\xa0a substanceʼs differential concentrations across a space or a membrane —\xa0but in living systems, gradients are more complex. Because ions move into and out of cells and because cells contain proteins that do not move across the membrane and are mostly negatively charged, there is also an electrical gradient, a difference of charge, across the plasma membrane.', '5aed8114-d399-45ab-9a93-39d29b148c07': 'The interior of living cells is electrically negative with respect to the extracellular fluid in which they are bathed, and at the same time, cells have higher concentrations of potassium (K+) and lower concentrations of sodium (Na+) than the extracellular fluid. Thus in a living cell, the concentration gradient of Na+ tends to drive it into the cell, and its electrical gradient (a positive ion) also drives it inward to the negatively charged interior. However, the situation is more complex for other elements such as potassium. The electrical gradient of K+, a positive ion, also drives it into the cell, but the concentration gradient of K+ drives K+ out of the cell (figure 16.9). We call the combined concentration gradient and electrical charge that affects an ion its electrochemical gradient.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 16.10,cell_bio/images/Figure 16.10.jpg,Figure 16.10: Different types of carrier proteins for active transport.,An important membrane adaptation for active transport is the presence of specific carrier proteins or pumps to facilitate movement. There are three protein types or transporters (figure 16.10).,"{'7c1a33aa-913e-41d8-8aa2-39b34a888287': 'An important membrane adaptation for active transport is the presence of specific carrier proteins or pumps to facilitate movement.\xa0There are three protein types or transporters (figure 16.10).', 'ee00c13b-f472-422c-a746-01152e74316a': 'All of these transporters can also transport small, uncharged organic molecules like glucose. These three types of carrier proteins are also in facilitated diffusion, but they do not require ATP to work in that process.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 16.11,cell_bio/images/Figure 16.11.jpg,Figure 16.11: Primary active transport.,The primary active transport that functions with the active transport of sodium and potassium allows secondary active transport to occur. The second transport method is still active because it depends on using energy as does primary transport (figure 16.11).,"{'b639ad1c-a650-448e-80d6-6cd69a936402': 'The primary active transport that functions with the active transport of sodium and potassium allows secondary active transport to occur. The second transport method is still active because it depends on using energy as does primary transport (figure 16.11).', '1775a1f9-4e20-4993-8eda-677b4596c87b': 'One of the most important pumps in animal cells is the sodium-potassium pump (Na+-K+ ATPase), which maintains the electrochemical gradient (and the correct concentrations of Na+ and K+) in living cells. The sodium-potassium pump moves K+ into the cell while moving Na+ out at the same time, at a ratio of three Na+ for every two K+ ions moved in. The Na+-K+ ATPase exists in two forms, depending on its orientation to the cellʼs interior or exterior and its affinity for either sodium or potassium ions. The process consists of the following six steps.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 16.9,cell_bio/images/Figure 16.9.jpg,Figure 16.9: Electrochemical gradients.,"The interior of living cells is electrically negative with respect to the extracellular fluid in which they are bathed, and at the same time, cells have higher concentrations of potassium (K+) and lower concentrations of sodium (Na+) than the extracellular fluid. Thus in a living cell, the concentration gradient of Na+ tends to drive it into the cell, and its electrical gradient (a positive ion) also drives it inward to the negatively charged interior. However, the situation is more complex for other elements such as potassium. The electrical gradient of K+, a positive ion, also drives it into the cell, but the concentration gradient of K+ drives K+ out of the cell (figure 16.9). We call the combined concentration gradient and electrical charge that affects an ion its electrochemical gradient.","{'592203af-40f2-4feb-9c5d-549ae9bc410a': 'We have discussed simple concentration gradients —\xa0a substanceʼs differential concentrations across a space or a membrane —\xa0but in living systems, gradients are more complex. Because ions move into and out of cells and because cells contain proteins that do not move across the membrane and are mostly negatively charged, there is also an electrical gradient, a difference of charge, across the plasma membrane.', '5aed8114-d399-45ab-9a93-39d29b148c07': 'The interior of living cells is electrically negative with respect to the extracellular fluid in which they are bathed, and at the same time, cells have higher concentrations of potassium (K+) and lower concentrations of sodium (Na+) than the extracellular fluid. Thus in a living cell, the concentration gradient of Na+ tends to drive it into the cell, and its electrical gradient (a positive ion) also drives it inward to the negatively charged interior. However, the situation is more complex for other elements such as potassium. The electrical gradient of K+, a positive ion, also drives it into the cell, but the concentration gradient of K+ drives K+ out of the cell (figure 16.9). We call the combined concentration gradient and electrical charge that affects an ion its electrochemical gradient.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 16.10,cell_bio/images/Figure 16.10.jpg,Figure 16.10: Different types of carrier proteins for active transport.,An important membrane adaptation for active transport is the presence of specific carrier proteins or pumps to facilitate movement. There are three protein types or transporters (figure 16.10).,"{'7c1a33aa-913e-41d8-8aa2-39b34a888287': 'An important membrane adaptation for active transport is the presence of specific carrier proteins or pumps to facilitate movement.\xa0There are three protein types or transporters (figure 16.10).', 'ee00c13b-f472-422c-a746-01152e74316a': 'All of these transporters can also transport small, uncharged organic molecules like glucose. These three types of carrier proteins are also in facilitated diffusion, but they do not require ATP to work in that process.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 16.11,cell_bio/images/Figure 16.11.jpg,Figure 16.11: Primary active transport.,The primary active transport that functions with the active transport of sodium and potassium allows secondary active transport to occur. The second transport method is still active because it depends on using energy as does primary transport (figure 16.11).,"{'b639ad1c-a650-448e-80d6-6cd69a936402': 'The primary active transport that functions with the active transport of sodium and potassium allows secondary active transport to occur. The second transport method is still active because it depends on using energy as does primary transport (figure 16.11).', '1775a1f9-4e20-4993-8eda-677b4596c87b': 'One of the most important pumps in animal cells is the sodium-potassium pump (Na+-K+ ATPase), which maintains the electrochemical gradient (and the correct concentrations of Na+ and K+) in living cells. The sodium-potassium pump moves K+ into the cell while moving Na+ out at the same time, at a ratio of three Na+ for every two K+ ions moved in. The Na+-K+ ATPase exists in two forms, depending on its orientation to the cellʼs interior or exterior and its affinity for either sodium or potassium ions. The process consists of the following six steps.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 15.1,cell_bio/images/Figure 15.1.jpg,Figure 15.1: Summary of types of cell signaling.,"Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):","{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.', 'b0fff953-f683-4a4e-913d-f3121f7388e0': 'Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.', '17707305-a984-4dcb-bce5-09f5714567b6': 'NO has a very short half-life and, therefore, only functions over short distances. It activates guanylyl cyclase to synthesize cGMP. This in turn results in smooth muscle relaxation.', 'c372d548-9d92-41a6-baf5-21da6998b388': 'Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra (erection involves dilated blood vessels).', '24559bee-77d1-4eb8-8620-c28e5020d266': '15.1 References and resources', 'e8322c26-db78-49a3-b8dd-b45b0c71ad1f': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 9: Cell Communication, Chapter 10: Cell Reproduction.', 'd4dfe93a-b6fb-4aff-ad3c-fcb46143b6ff': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 15: Cell Signaling and Signal Transduction.', '758dc906-b92f-4b14-a2fc-aa133168286d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 85, 208, 238.', '6af147b6-1810-4da0-a36a-5796f8e0ea98': '15.2 Apoptosis', '6cad671f-c018-410c-9f66-a3fe485377fd': 'Both cell proliferation and apoptosis (controlled/programed cell death) are decisive processes within a cell. Keep in mind, apoptosis is distinct from cell necrosis, in which cell death is usually attributable to physical or chemical damage and rapidly spontaneous; think explosion.', '8706319e-1bbe-43b8-91c8-6f112a40d628': 'Apoptosis is genetically programmed cell death, which leads to “tidy” breakdown and disposal of cells. Morphologically, apoptosis is characterized by shrinking of the cell, changes in the cell membrane (with the formation of small blebs known as “apoptotic bodies”), shrinking of the nucleus, chromatin condensation, and fragmentation of DNA. Macrophages and other phagocytic cells recognize this signal and remove apoptotic cells by phagocytosis without inflammatory phenomena developing. Apoptosis regulates the growth of normal tissues and removes unwanted cells in a controlled manner.', '1e55f670-59fc-41c7-af6c-593280627676': 'Caspases are a family of enzymes that control this process. These are cysteine proteases that\xa0cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which\xa0are able to fragment the nuclear DNA (figure 15.6).'}"
Figure 15.3,cell_bio/images/Figure 15.3.jpg,Figure 15.3: Common G-protein-coupled receptor signaling cascade.,"The classic cascade starts with hormone binding, to an extracellular domain of a seven-helix receptor (GPCR), which causes a conformational change in the receptor that is transmitted to a G protein on the cytosolic side of the membrane (figure 15.3).","{'c69f7d88-963f-43a4-897f-56138a3a5d55': 'G-protein-coupled receptors (GPCR) can come in several different classes: Gαs, Gαi, and Gαq. Activation of a Gαs (activated by glucagon) will increase the second messenger cAMP, while both Gαi or Gαt cascades function to reduce cAMP, either through inhibition of adenylyl cyclase (also known as adenylate cyclase) or through activation of phosphodiesterase, respectively.', '4f207cd9-a49f-4df1-9cbb-6924f30aceb5': 'The classic cascade starts with hormone binding, to an extracellular domain of a seven-helix receptor (GPCR), which causes a conformational change in the receptor that is transmitted to a G protein on the cytosolic side of the membrane (figure 15.3).', 'b0fff953-f683-4a4e-913d-f3121f7388e0': 'Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.', '17707305-a984-4dcb-bce5-09f5714567b6': 'NO has a very short half-life and, therefore, only functions over short distances. It activates guanylyl cyclase to synthesize cGMP. This in turn results in smooth muscle relaxation.', 'c372d548-9d92-41a6-baf5-21da6998b388': 'Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra (erection involves dilated blood vessels).', '24559bee-77d1-4eb8-8620-c28e5020d266': '15.1 References and resources', 'e8322c26-db78-49a3-b8dd-b45b0c71ad1f': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 9: Cell Communication, Chapter 10: Cell Reproduction.', 'd4dfe93a-b6fb-4aff-ad3c-fcb46143b6ff': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 15: Cell Signaling and Signal Transduction.', '758dc906-b92f-4b14-a2fc-aa133168286d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 85, 208, 238.', '6af147b6-1810-4da0-a36a-5796f8e0ea98': '15.2 Apoptosis', '6cad671f-c018-410c-9f66-a3fe485377fd': 'Both cell proliferation and apoptosis (controlled/programed cell death) are decisive processes within a cell. Keep in mind, apoptosis is distinct from cell necrosis, in which cell death is usually attributable to physical or chemical damage and rapidly spontaneous; think explosion.', '8706319e-1bbe-43b8-91c8-6f112a40d628': 'Apoptosis is genetically programmed cell death, which leads to “tidy” breakdown and disposal of cells. Morphologically, apoptosis is characterized by shrinking of the cell, changes in the cell membrane (with the formation of small blebs known as “apoptotic bodies”), shrinking of the nucleus, chromatin condensation, and fragmentation of DNA. Macrophages and other phagocytic cells recognize this signal and remove apoptotic cells by phagocytosis without inflammatory phenomena developing. Apoptosis regulates the growth of normal tissues and removes unwanted cells in a controlled manner.', '1e55f670-59fc-41c7-af6c-593280627676': 'Caspases are a family of enzymes that control this process. These are cysteine proteases that\xa0cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which\xa0are able to fragment the nuclear DNA (figure 15.6).'}"
Figure 15.4,cell_bio/images/Figure 15.4.jpg,Figure 15.4: Signaling cascade initiated by DAG and IP3.,Phosphatidylinositols are membrane-bound compounds that can be phosphorylated or cleaved to function as second messengers in a signaling cascade (figure 15.4).,"{'0ef9d026-dd74-4257-8a9c-d956a9d8ad65': 'Phosphatidylinositols are membrane-bound compounds that can be phosphorylated or cleaved to function as second messengers in a signaling cascade (figure 15.4).', '8c84013d-f70e-4dfb-93db-8d1c7b3a8ca5': 'The common membrane component, phosphatidylinositol (PI), can be phosphorylated (by any number of kinases) to form PI 4,5-bisphosphate. This molecule can\xa0undergo two different fates.', 'f6c6d4f5-af94-4dfd-b13f-14fdb087e9d6': 'This cascade will become important for calcium signaling, which is modulated through interactions of IP3 with the mitochondria.', '321fbd6d-c0cb-42c9-9944-6330ed19145a': 'Changes in intracellular calcium can alter membrane permeability through calcium-induced calcium release.', 'b0fff953-f683-4a4e-913d-f3121f7388e0': 'Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.', '17707305-a984-4dcb-bce5-09f5714567b6': 'NO has a very short half-life and, therefore, only functions over short distances. It activates guanylyl cyclase to synthesize cGMP. This in turn results in smooth muscle relaxation.', 'c372d548-9d92-41a6-baf5-21da6998b388': 'Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra (erection involves dilated blood vessels).', '24559bee-77d1-4eb8-8620-c28e5020d266': '15.1 References and resources', 'e8322c26-db78-49a3-b8dd-b45b0c71ad1f': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 9: Cell Communication, Chapter 10: Cell Reproduction.', 'd4dfe93a-b6fb-4aff-ad3c-fcb46143b6ff': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 15: Cell Signaling and Signal Transduction.', '758dc906-b92f-4b14-a2fc-aa133168286d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 85, 208, 238.', '6af147b6-1810-4da0-a36a-5796f8e0ea98': '15.2 Apoptosis', '6cad671f-c018-410c-9f66-a3fe485377fd': 'Both cell proliferation and apoptosis (controlled/programed cell death) are decisive processes within a cell. Keep in mind, apoptosis is distinct from cell necrosis, in which cell death is usually attributable to physical or chemical damage and rapidly spontaneous; think explosion.', '8706319e-1bbe-43b8-91c8-6f112a40d628': 'Apoptosis is genetically programmed cell death, which leads to “tidy” breakdown and disposal of cells. Morphologically, apoptosis is characterized by shrinking of the cell, changes in the cell membrane (with the formation of small blebs known as “apoptotic bodies”), shrinking of the nucleus, chromatin condensation, and fragmentation of DNA. Macrophages and other phagocytic cells recognize this signal and remove apoptotic cells by phagocytosis without inflammatory phenomena developing. Apoptosis regulates the growth of normal tissues and removes unwanted cells in a controlled manner.', '1e55f670-59fc-41c7-af6c-593280627676': 'Caspases are a family of enzymes that control this process. These are cysteine proteases that\xa0cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which\xa0are able to fragment the nuclear DNA (figure 15.6).'}"
Figure 15.1,cell_bio/images/Figure 15.1.jpg,Figure 15.1: Summary of types of cell signaling.,"Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):","{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.', 'b0fff953-f683-4a4e-913d-f3121f7388e0': 'Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.', '17707305-a984-4dcb-bce5-09f5714567b6': 'NO has a very short half-life and, therefore, only functions over short distances. It activates guanylyl cyclase to synthesize cGMP. This in turn results in smooth muscle relaxation.', 'c372d548-9d92-41a6-baf5-21da6998b388': 'Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra (erection involves dilated blood vessels).', '24559bee-77d1-4eb8-8620-c28e5020d266': '15.1 References and resources', 'e8322c26-db78-49a3-b8dd-b45b0c71ad1f': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 9: Cell Communication, Chapter 10: Cell Reproduction.', 'd4dfe93a-b6fb-4aff-ad3c-fcb46143b6ff': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 15: Cell Signaling and Signal Transduction.', '758dc906-b92f-4b14-a2fc-aa133168286d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 85, 208, 238.', '6af147b6-1810-4da0-a36a-5796f8e0ea98': '15.2 Apoptosis', '6cad671f-c018-410c-9f66-a3fe485377fd': 'Both cell proliferation and apoptosis (controlled/programed cell death) are decisive processes within a cell. Keep in mind, apoptosis is distinct from cell necrosis, in which cell death is usually attributable to physical or chemical damage and rapidly spontaneous; think explosion.', '8706319e-1bbe-43b8-91c8-6f112a40d628': 'Apoptosis is genetically programmed cell death, which leads to “tidy” breakdown and disposal of cells. Morphologically, apoptosis is characterized by shrinking of the cell, changes in the cell membrane (with the formation of small blebs known as “apoptotic bodies”), shrinking of the nucleus, chromatin condensation, and fragmentation of DNA. Macrophages and other phagocytic cells recognize this signal and remove apoptotic cells by phagocytosis without inflammatory phenomena developing. Apoptosis regulates the growth of normal tissues and removes unwanted cells in a controlled manner.', '1e55f670-59fc-41c7-af6c-593280627676': 'Caspases are a family of enzymes that control this process. These are cysteine proteases that\xa0cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which\xa0are able to fragment the nuclear DNA (figure 15.6).'}"
Figure 15.2,cell_bio/images/Figure 15.2.jpg,,Figure 15.2: Examples of steroid hormones.,"{'b0fff953-f683-4a4e-913d-f3121f7388e0': 'Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.', '17707305-a984-4dcb-bce5-09f5714567b6': 'NO has a very short half-life and, therefore, only functions over short distances. It activates guanylyl cyclase to synthesize cGMP. This in turn results in smooth muscle relaxation.', 'c372d548-9d92-41a6-baf5-21da6998b388': 'Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra (erection involves dilated blood vessels).', '24559bee-77d1-4eb8-8620-c28e5020d266': '15.1 References and resources', 'e8322c26-db78-49a3-b8dd-b45b0c71ad1f': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 9: Cell Communication, Chapter 10: Cell Reproduction.', 'd4dfe93a-b6fb-4aff-ad3c-fcb46143b6ff': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 15: Cell Signaling and Signal Transduction.', '758dc906-b92f-4b14-a2fc-aa133168286d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 85, 208, 238.', '6af147b6-1810-4da0-a36a-5796f8e0ea98': '15.2 Apoptosis', '6cad671f-c018-410c-9f66-a3fe485377fd': 'Both cell proliferation and apoptosis (controlled/programed cell death) are decisive processes within a cell. Keep in mind, apoptosis is distinct from cell necrosis, in which cell death is usually attributable to physical or chemical damage and rapidly spontaneous; think explosion.', '8706319e-1bbe-43b8-91c8-6f112a40d628': 'Apoptosis is genetically programmed cell death, which leads to “tidy” breakdown and disposal of cells. Morphologically, apoptosis is characterized by shrinking of the cell, changes in the cell membrane (with the formation of small blebs known as “apoptotic bodies”), shrinking of the nucleus, chromatin condensation, and fragmentation of DNA. Macrophages and other phagocytic cells recognize this signal and remove apoptotic cells by phagocytosis without inflammatory phenomena developing. Apoptosis regulates the growth of normal tissues and removes unwanted cells in a controlled manner.', '1e55f670-59fc-41c7-af6c-593280627676': 'Caspases are a family of enzymes that control this process. These are cysteine proteases that\xa0cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which\xa0are able to fragment the nuclear DNA (figure 15.6).'}"
Figure 15.3,cell_bio/images/Figure 15.3.jpg,Figure 15.3: Common G-protein-coupled receptor signaling cascade.,"The classic cascade starts with hormone binding, to an extracellular domain of a seven-helix receptor (GPCR), which causes a conformational change in the receptor that is transmitted to a G protein on the cytosolic side of the membrane (figure 15.3).","{'c69f7d88-963f-43a4-897f-56138a3a5d55': 'G-protein-coupled receptors (GPCR) can come in several different classes: Gαs, Gαi, and Gαq. Activation of a Gαs (activated by glucagon) will increase the second messenger cAMP, while both Gαi or Gαt cascades function to reduce cAMP, either through inhibition of adenylyl cyclase (also known as adenylate cyclase) or through activation of phosphodiesterase, respectively.', '4f207cd9-a49f-4df1-9cbb-6924f30aceb5': 'The classic cascade starts with hormone binding, to an extracellular domain of a seven-helix receptor (GPCR), which causes a conformational change in the receptor that is transmitted to a G protein on the cytosolic side of the membrane (figure 15.3).', 'b0fff953-f683-4a4e-913d-f3121f7388e0': 'Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.', '17707305-a984-4dcb-bce5-09f5714567b6': 'NO has a very short half-life and, therefore, only functions over short distances. It activates guanylyl cyclase to synthesize cGMP. This in turn results in smooth muscle relaxation.', 'c372d548-9d92-41a6-baf5-21da6998b388': 'Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra (erection involves dilated blood vessels).', '24559bee-77d1-4eb8-8620-c28e5020d266': '15.1 References and resources', 'e8322c26-db78-49a3-b8dd-b45b0c71ad1f': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 9: Cell Communication, Chapter 10: Cell Reproduction.', 'd4dfe93a-b6fb-4aff-ad3c-fcb46143b6ff': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 15: Cell Signaling and Signal Transduction.', '758dc906-b92f-4b14-a2fc-aa133168286d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 85, 208, 238.', '6af147b6-1810-4da0-a36a-5796f8e0ea98': '15.2 Apoptosis', '6cad671f-c018-410c-9f66-a3fe485377fd': 'Both cell proliferation and apoptosis (controlled/programed cell death) are decisive processes within a cell. Keep in mind, apoptosis is distinct from cell necrosis, in which cell death is usually attributable to physical or chemical damage and rapidly spontaneous; think explosion.', '8706319e-1bbe-43b8-91c8-6f112a40d628': 'Apoptosis is genetically programmed cell death, which leads to “tidy” breakdown and disposal of cells. Morphologically, apoptosis is characterized by shrinking of the cell, changes in the cell membrane (with the formation of small blebs known as “apoptotic bodies”), shrinking of the nucleus, chromatin condensation, and fragmentation of DNA. Macrophages and other phagocytic cells recognize this signal and remove apoptotic cells by phagocytosis without inflammatory phenomena developing. Apoptosis regulates the growth of normal tissues and removes unwanted cells in a controlled manner.', '1e55f670-59fc-41c7-af6c-593280627676': 'Caspases are a family of enzymes that control this process. These are cysteine proteases that\xa0cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which\xa0are able to fragment the nuclear DNA (figure 15.6).'}"
Figure 15.4,cell_bio/images/Figure 15.4.jpg,Figure 15.4: Signaling cascade initiated by DAG and IP3.,Phosphatidylinositols are membrane-bound compounds that can be phosphorylated or cleaved to function as second messengers in a signaling cascade (figure 15.4).,"{'0ef9d026-dd74-4257-8a9c-d956a9d8ad65': 'Phosphatidylinositols are membrane-bound compounds that can be phosphorylated or cleaved to function as second messengers in a signaling cascade (figure 15.4).', '8c84013d-f70e-4dfb-93db-8d1c7b3a8ca5': 'The common membrane component, phosphatidylinositol (PI), can be phosphorylated (by any number of kinases) to form PI 4,5-bisphosphate. This molecule can\xa0undergo two different fates.', 'f6c6d4f5-af94-4dfd-b13f-14fdb087e9d6': 'This cascade will become important for calcium signaling, which is modulated through interactions of IP3 with the mitochondria.', '321fbd6d-c0cb-42c9-9944-6330ed19145a': 'Changes in intracellular calcium can alter membrane permeability through calcium-induced calcium release.', 'b0fff953-f683-4a4e-913d-f3121f7388e0': 'Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.', '17707305-a984-4dcb-bce5-09f5714567b6': 'NO has a very short half-life and, therefore, only functions over short distances. It activates guanylyl cyclase to synthesize cGMP. This in turn results in smooth muscle relaxation.', 'c372d548-9d92-41a6-baf5-21da6998b388': 'Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra (erection involves dilated blood vessels).', '24559bee-77d1-4eb8-8620-c28e5020d266': '15.1 References and resources', 'e8322c26-db78-49a3-b8dd-b45b0c71ad1f': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 9: Cell Communication, Chapter 10: Cell Reproduction.', 'd4dfe93a-b6fb-4aff-ad3c-fcb46143b6ff': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 15: Cell Signaling and Signal Transduction.', '758dc906-b92f-4b14-a2fc-aa133168286d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 85, 208, 238.', '6af147b6-1810-4da0-a36a-5796f8e0ea98': '15.2 Apoptosis', '6cad671f-c018-410c-9f66-a3fe485377fd': 'Both cell proliferation and apoptosis (controlled/programed cell death) are decisive processes within a cell. Keep in mind, apoptosis is distinct from cell necrosis, in which cell death is usually attributable to physical or chemical damage and rapidly spontaneous; think explosion.', '8706319e-1bbe-43b8-91c8-6f112a40d628': 'Apoptosis is genetically programmed cell death, which leads to “tidy” breakdown and disposal of cells. Morphologically, apoptosis is characterized by shrinking of the cell, changes in the cell membrane (with the formation of small blebs known as “apoptotic bodies”), shrinking of the nucleus, chromatin condensation, and fragmentation of DNA. Macrophages and other phagocytic cells recognize this signal and remove apoptotic cells by phagocytosis without inflammatory phenomena developing. Apoptosis regulates the growth of normal tissues and removes unwanted cells in a controlled manner.', '1e55f670-59fc-41c7-af6c-593280627676': 'Caspases are a family of enzymes that control this process. These are cysteine proteases that\xa0cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which\xa0are able to fragment the nuclear DNA (figure 15.6).'}"
Figure 15.5,cell_bio/images/Figure 15.5.jpg,,Figure 15.5: Receptor tyrosine kinase signaling.,"{'b0fff953-f683-4a4e-913d-f3121f7388e0': 'Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.', '17707305-a984-4dcb-bce5-09f5714567b6': 'NO has a very short half-life and, therefore, only functions over short distances. It activates guanylyl cyclase to synthesize cGMP. This in turn results in smooth muscle relaxation.', 'c372d548-9d92-41a6-baf5-21da6998b388': 'Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra (erection involves dilated blood vessels).', '24559bee-77d1-4eb8-8620-c28e5020d266': '15.1 References and resources', 'e8322c26-db78-49a3-b8dd-b45b0c71ad1f': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 9: Cell Communication, Chapter 10: Cell Reproduction.', 'd4dfe93a-b6fb-4aff-ad3c-fcb46143b6ff': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 15: Cell Signaling and Signal Transduction.', '758dc906-b92f-4b14-a2fc-aa133168286d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 85, 208, 238.', '6af147b6-1810-4da0-a36a-5796f8e0ea98': '15.2 Apoptosis', '6cad671f-c018-410c-9f66-a3fe485377fd': 'Both cell proliferation and apoptosis (controlled/programed cell death) are decisive processes within a cell. Keep in mind, apoptosis is distinct from cell necrosis, in which cell death is usually attributable to physical or chemical damage and rapidly spontaneous; think explosion.', '8706319e-1bbe-43b8-91c8-6f112a40d628': 'Apoptosis is genetically programmed cell death, which leads to “tidy” breakdown and disposal of cells. Morphologically, apoptosis is characterized by shrinking of the cell, changes in the cell membrane (with the formation of small blebs known as “apoptotic bodies”), shrinking of the nucleus, chromatin condensation, and fragmentation of DNA. Macrophages and other phagocytic cells recognize this signal and remove apoptotic cells by phagocytosis without inflammatory phenomena developing. Apoptosis regulates the growth of normal tissues and removes unwanted cells in a controlled manner.', '1e55f670-59fc-41c7-af6c-593280627676': 'Caspases are a family of enzymes that control this process. These are cysteine proteases that\xa0cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which\xa0are able to fragment the nuclear DNA (figure 15.6).'}"
Figure 15.6,cell_bio/images/Figure 15.6.jpg,Figure 15.6: Comparison of intrinsic and extrinsic apoptosis pathways.,"Caspases are a family of enzymes that control this process. These are cysteine proteases that cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which are able to fragment the nuclear DNA (figure 15.6).","{'b0fff953-f683-4a4e-913d-f3121f7388e0': 'Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.', '17707305-a984-4dcb-bce5-09f5714567b6': 'NO has a very short half-life and, therefore, only functions over short distances. It activates guanylyl cyclase to synthesize cGMP. This in turn results in smooth muscle relaxation.', 'c372d548-9d92-41a6-baf5-21da6998b388': 'Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra (erection involves dilated blood vessels).', '24559bee-77d1-4eb8-8620-c28e5020d266': '15.1 References and resources', 'e8322c26-db78-49a3-b8dd-b45b0c71ad1f': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 9: Cell Communication, Chapter 10: Cell Reproduction.', 'd4dfe93a-b6fb-4aff-ad3c-fcb46143b6ff': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 15: Cell Signaling and Signal Transduction.', '758dc906-b92f-4b14-a2fc-aa133168286d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 85, 208, 238.', '6af147b6-1810-4da0-a36a-5796f8e0ea98': '15.2 Apoptosis', '6cad671f-c018-410c-9f66-a3fe485377fd': 'Both cell proliferation and apoptosis (controlled/programed cell death) are decisive processes within a cell. Keep in mind, apoptosis is distinct from cell necrosis, in which cell death is usually attributable to physical or chemical damage and rapidly spontaneous; think explosion.', '8706319e-1bbe-43b8-91c8-6f112a40d628': 'Apoptosis is genetically programmed cell death, which leads to “tidy” breakdown and disposal of cells. Morphologically, apoptosis is characterized by shrinking of the cell, changes in the cell membrane (with the formation of small blebs known as “apoptotic bodies”), shrinking of the nucleus, chromatin condensation, and fragmentation of DNA. Macrophages and other phagocytic cells recognize this signal and remove apoptotic cells by phagocytosis without inflammatory phenomena developing. Apoptosis regulates the growth of normal tissues and removes unwanted cells in a controlled manner.', '1e55f670-59fc-41c7-af6c-593280627676': 'Caspases are a family of enzymes that control this process. These are cysteine proteases that\xa0cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which\xa0are able to fragment the nuclear DNA (figure 15.6).', 'ece97080-3152-4b73-a754-86cb2cd01e04': 'The intrinsic, mitochondrial pathway is triggered by genotoxic (DNA damage) or oxidative stress. Aided by Bcl proteins, chemical stress makes the outer mitochondrial membrane leaky. As a result, mitochondrial proteins reach the cytoplasm. Cytochrome c in particular then triggers the caspase cascade by binding to the adapter protein Apaf1 and promoting formation of an apoptosome, a wheel-shaped heptamer that recruits initiator procaspase 9 and activates it to caspase\xa09.', 'c19d8db4-e9b5-44c0-8d6b-ed28366b30da': 'The Bcl protein family not only includes proapoptotic proteins (Bax, Bak, and Bim) but also proteins that inhibit apoptosis (including Bcl2). Extracellular growth factors ensure inactivation of Bad or replication of Bcl 2, thus preventing apoptosis.', 'a20a473d-9d5e-4284-95cc-4a9b3e94c271': '15.2 References and resources', '9aa89210-9ac5-4c00-a2b3-a64d8b6be901': '15.3 Membrane Potential', 'c4397bc4-7135-4bfd-b860-b813ae1bf1f7': 'The electrical state of the cell membrane can have several variations. These are all variations in the membrane potential. A potential is a distribution of charge across the cell membrane, measured in millivolts (mV). The standard is to compare the inside of the cell relative to the outside, so the membrane potential is a value representing the charge on the intracellular side of the membrane based on the outside being zero, relatively speaking. Neurons harvest this membrane potential to generate or propagate a nerve impulse (figure 15.7).'}"
Figure 15.6,cell_bio/images/Figure 15.6.jpg,Figure 15.6: Comparison of intrinsic and extrinsic apoptosis pathways.,"Caspases are a family of enzymes that control this process. These are cysteine proteases that cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which are able to fragment the nuclear DNA (figure 15.6).","{'b0fff953-f683-4a4e-913d-f3121f7388e0': 'Nitric oxide NO is a gas that also acts as a ligand. It is able to diffuse directly across the plasma membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of the tissue.', '17707305-a984-4dcb-bce5-09f5714567b6': 'NO has a very short half-life and, therefore, only functions over short distances. It activates guanylyl cyclase to synthesize cGMP. This in turn results in smooth muscle relaxation.', 'c372d548-9d92-41a6-baf5-21da6998b388': 'Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart. NO has become better known recently because the pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra (erection involves dilated blood vessels).', '24559bee-77d1-4eb8-8620-c28e5020d266': '15.1 References and resources', 'e8322c26-db78-49a3-b8dd-b45b0c71ad1f': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 9: Cell Communication, Chapter 10: Cell Reproduction.', 'd4dfe93a-b6fb-4aff-ad3c-fcb46143b6ff': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 15: Cell Signaling and Signal Transduction.', '758dc906-b92f-4b14-a2fc-aa133168286d': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 85, 208, 238.', '6af147b6-1810-4da0-a36a-5796f8e0ea98': '15.2 Apoptosis', '6cad671f-c018-410c-9f66-a3fe485377fd': 'Both cell proliferation and apoptosis (controlled/programed cell death) are decisive processes within a cell. Keep in mind, apoptosis is distinct from cell necrosis, in which cell death is usually attributable to physical or chemical damage and rapidly spontaneous; think explosion.', '8706319e-1bbe-43b8-91c8-6f112a40d628': 'Apoptosis is genetically programmed cell death, which leads to “tidy” breakdown and disposal of cells. Morphologically, apoptosis is characterized by shrinking of the cell, changes in the cell membrane (with the formation of small blebs known as “apoptotic bodies”), shrinking of the nucleus, chromatin condensation, and fragmentation of DNA. Macrophages and other phagocytic cells recognize this signal and remove apoptotic cells by phagocytosis without inflammatory phenomena developing. Apoptosis regulates the growth of normal tissues and removes unwanted cells in a controlled manner.', '1e55f670-59fc-41c7-af6c-593280627676': 'Caspases are a family of enzymes that control this process. These are cysteine proteases that\xa0cleave proteins next to aspartate residues when they become activated. When a cell receives an apoptotic signal, the procaspases become active and begin the process of protein degradation starting with the cleavage of laminins in the nuclear envelope, protein kinases, transcription factors, snRP proteins, and inhibitors of special DNAses, which\xa0are able to fragment the nuclear DNA (figure 15.6).', 'ece97080-3152-4b73-a754-86cb2cd01e04': 'The intrinsic, mitochondrial pathway is triggered by genotoxic (DNA damage) or oxidative stress. Aided by Bcl proteins, chemical stress makes the outer mitochondrial membrane leaky. As a result, mitochondrial proteins reach the cytoplasm. Cytochrome c in particular then triggers the caspase cascade by binding to the adapter protein Apaf1 and promoting formation of an apoptosome, a wheel-shaped heptamer that recruits initiator procaspase 9 and activates it to caspase\xa09.', 'c19d8db4-e9b5-44c0-8d6b-ed28366b30da': 'The Bcl protein family not only includes proapoptotic proteins (Bax, Bak, and Bim) but also proteins that inhibit apoptosis (including Bcl2). Extracellular growth factors ensure inactivation of Bad or replication of Bcl 2, thus preventing apoptosis.', 'a20a473d-9d5e-4284-95cc-4a9b3e94c271': '15.2 References and resources', '9aa89210-9ac5-4c00-a2b3-a64d8b6be901': '15.3 Membrane Potential', 'c4397bc4-7135-4bfd-b860-b813ae1bf1f7': 'The electrical state of the cell membrane can have several variations. These are all variations in the membrane potential. A potential is a distribution of charge across the cell membrane, measured in millivolts (mV). The standard is to compare the inside of the cell relative to the outside, so the membrane potential is a value representing the charge on the intracellular side of the membrane based on the outside being zero, relatively speaking. Neurons harvest this membrane potential to generate or propagate a nerve impulse (figure 15.7).'}"
Figure 15.7,cell_bio/images/Figure 15.7.jpg,Figure 15.7: Neurotransmission by acetylcholine.,"The electrical state of the cell membrane can have several variations. These are all variations in the membrane potential. A potential is a distribution of charge across the cell membrane, measured in millivolts (mV). The standard is to compare the inside of the cell relative to the outside, so the membrane potential is a value representing the charge on the intracellular side of the membrane based on the outside being zero, relatively speaking. Neurons harvest this membrane potential to generate or propagate a nerve impulse (figure 15.7).","{'ece97080-3152-4b73-a754-86cb2cd01e04': 'The intrinsic, mitochondrial pathway is triggered by genotoxic (DNA damage) or oxidative stress. Aided by Bcl proteins, chemical stress makes the outer mitochondrial membrane leaky. As a result, mitochondrial proteins reach the cytoplasm. Cytochrome c in particular then triggers the caspase cascade by binding to the adapter protein Apaf1 and promoting formation of an apoptosome, a wheel-shaped heptamer that recruits initiator procaspase 9 and activates it to caspase\xa09.', 'c19d8db4-e9b5-44c0-8d6b-ed28366b30da': 'The Bcl protein family not only includes proapoptotic proteins (Bax, Bak, and Bim) but also proteins that inhibit apoptosis (including Bcl2). Extracellular growth factors ensure inactivation of Bad or replication of Bcl 2, thus preventing apoptosis.', 'a20a473d-9d5e-4284-95cc-4a9b3e94c271': '15.2 References and resources', '9aa89210-9ac5-4c00-a2b3-a64d8b6be901': '15.3 Membrane Potential', 'c4397bc4-7135-4bfd-b860-b813ae1bf1f7': 'The electrical state of the cell membrane can have several variations. These are all variations in the membrane potential. A potential is a distribution of charge across the cell membrane, measured in millivolts (mV). The standard is to compare the inside of the cell relative to the outside, so the membrane potential is a value representing the charge on the intracellular side of the membrane based on the outside being zero, relatively speaking. Neurons harvest this membrane potential to generate or propagate a nerve impulse (figure 15.7).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 15.7,cell_bio/images/Figure 15.7.jpg,Figure 15.7: Neurotransmission by acetylcholine.,"The electrical state of the cell membrane can have several variations. These are all variations in the membrane potential. A potential is a distribution of charge across the cell membrane, measured in millivolts (mV). The standard is to compare the inside of the cell relative to the outside, so the membrane potential is a value representing the charge on the intracellular side of the membrane based on the outside being zero, relatively speaking. Neurons harvest this membrane potential to generate or propagate a nerve impulse (figure 15.7).","{'ece97080-3152-4b73-a754-86cb2cd01e04': 'The intrinsic, mitochondrial pathway is triggered by genotoxic (DNA damage) or oxidative stress. Aided by Bcl proteins, chemical stress makes the outer mitochondrial membrane leaky. As a result, mitochondrial proteins reach the cytoplasm. Cytochrome c in particular then triggers the caspase cascade by binding to the adapter protein Apaf1 and promoting formation of an apoptosome, a wheel-shaped heptamer that recruits initiator procaspase 9 and activates it to caspase\xa09.', 'c19d8db4-e9b5-44c0-8d6b-ed28366b30da': 'The Bcl protein family not only includes proapoptotic proteins (Bax, Bak, and Bim) but also proteins that inhibit apoptosis (including Bcl2). Extracellular growth factors ensure inactivation of Bad or replication of Bcl 2, thus preventing apoptosis.', 'a20a473d-9d5e-4284-95cc-4a9b3e94c271': '15.2 References and resources', '9aa89210-9ac5-4c00-a2b3-a64d8b6be901': '15.3 Membrane Potential', 'c4397bc4-7135-4bfd-b860-b813ae1bf1f7': 'The electrical state of the cell membrane can have several variations. These are all variations in the membrane potential. A potential is a distribution of charge across the cell membrane, measured in millivolts (mV). The standard is to compare the inside of the cell relative to the outside, so the membrane potential is a value representing the charge on the intracellular side of the membrane based on the outside being zero, relatively speaking. Neurons harvest this membrane potential to generate or propagate a nerve impulse (figure 15.7).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 15.9,cell_bio/images/Figure 15.9.jpg,,Figure 15.9: Summary of the action potential as it relates to change in ion concentration across the membrane.,"{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 15.8,cell_bio/images/Figure 15.8.jpg,Figure 15.8: Summary of the action potential to membrane potential.,"Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.","{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 14.1,cell_bio/images/Figure 14.1.jpg,,Figure 14.1: Punnett square illustrating allelic distribution of recessive traits.,"{'21948c4d-0178-422d-8593-be4a974e84c4': '1 – 0.02 = 0.98 = p', '700187bb-ff1c-488b-b340-25c0141fd1dc': '14.1 References and resources', 'bdff4636-1d7b-47c9-aed3-773ba16621cd': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 12: Mendel’s Experiments and Heridity, Chapter 13: Modern Understandings of Inheritance.', 'f6a67306-8963-4d95-a9f2-8330504080e8': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 55–59.', '50b6d50a-3c9e-4be5-90af-0611fbed528b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 7: Patterns of Single Gene Inheritance, Chapter 9: Genetic Variations in Populations, Chapter 10: Identifying the Genetic Basis for Human Disease.'}"
Figure 14.2,cell_bio/images/Figure 14.2.jpg,,Figure 14.2: Allelic distributions in dominant traits.,"{'21948c4d-0178-422d-8593-be4a974e84c4': '1 – 0.02 = 0.98 = p', '700187bb-ff1c-488b-b340-25c0141fd1dc': '14.1 References and resources', 'bdff4636-1d7b-47c9-aed3-773ba16621cd': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 12: Mendel’s Experiments and Heridity, Chapter 13: Modern Understandings of Inheritance.', 'f6a67306-8963-4d95-a9f2-8330504080e8': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 55–59.', '50b6d50a-3c9e-4be5-90af-0611fbed528b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 7: Patterns of Single Gene Inheritance, Chapter 9: Genetic Variations in Populations, Chapter 10: Identifying the Genetic Basis for Human Disease.'}"
Figure 14.3,cell_bio/images/Figure 14.3.jpg,Figure 14.3: Graphic representation of penetrance and expressivity.,"Penetrance refers to the display of any signs or symptoms if you have the genetic abnormality; this does not describe the variety of phenotype. As illustrated in figure 14.3, this refers to the number of “affected (purple)” versus “unaffected (white)” cells in an individual. Individuals with a greater number of purple cells may have a more pronounced phenotype than individuals with greater numbers of white cells.","{'87b0abcd-4cd2-4dc1-bf29-07cd4bfc994c': '17.2 Endocytosis', 'b44f6426-7f61-492a-bb25-cca17ef783dd': '14.2 Non-Mendelian Inheritance', 'd1296041-94c4-4749-95bb-7c5387f35ff5': 'The majority of genetic disorders are not inherited in a Mendelian fashion. Even in cases where Mendelian genetics can predict genotype, the disease phenotype may not be displayed or may be variable due to external influences. This section describes some additional factors that influence presentation and inheritance patterns.', '72b8404a-4a28-4f4c-bc41-c30c39a353fa': 'Penetrance refers to the display of any signs or symptoms if you have the genetic abnormality; this\xa0does not describe the variety of phenotype. As illustrated in figure 14.3, this refers to the number of “affected (purple)” versus “unaffected (white)” cells in an individual. Individuals with a greater number of purple cells may have a more pronounced phenotype than individuals with greater numbers of white cells.', '51306d88-d853-4baa-9cbf-2cdf55e39cb7': 'Variable phenotypes can present due to changes in expressivity or pleiotropy. These terms refer to the variety of presentations from a single genetic disorder\xa0(variable expression). As illustrated in figure 14.3, expressivity can be a range of “purplish”\xa0colors, which may give rise to a variable phenotype. In other more complicated genetic cases, both penetrance and expressivity must be considered when making a diagnosis. Pleiotropy of a disorder is best described as a single gene disorder having implications on several different organ systems.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 14.4,cell_bio/images/Figure 14.4.jpg,Figure 14.4: Mitochondrial inheritance pattern.,"Therefore in this inheritance modality, the females can transmit the trait to all offspring (figure 14.4), however, only female offspring will continue to transmit the disorder. Disease phenotype in mitochondrial disease is extremely variable due to mitochondrial heteroplasmy.","{'546505ca-2408-4d24-9d61-57a21542b1f5': 'Mitochondria are unique in that they have multiple copies of a circular chromosome. This DNA is independent of nuclear DNA and inherited from the mother.', 'f9a83560-60fd-4e80-a82d-7ac388c514fe': 'Therefore in this inheritance modality, the females can transmit the trait to all offspring (figure 14.4), however, only female offspring will continue to transmit the disorder. Disease phenotype in mitochondrial disease is extremely variable due to mitochondrial heteroplasmy.', '1e3f5a07-6c9c-4ed6-b7f4-ceaf8d97ab9f': 'Heteroplasmy is a term referring to the diversity of the mitochondrial genome within each cell. During cell division, mitochondria are divided randomly between the two daughter cells, and therefore the percentage of affected mitochondrial DNA (mtDNA) will also be variable within the offspring. The mitochondria generate energy for the rest of the cell, therefore disease transmitted through mitochondrial inheritance affects high-energy organs (this is a good example of pleiotropy).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 14.5,cell_bio/images/Figure 14.5.jpg,Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease.,"Disorders in this category are caused by expansion of tandem trinucleotide repeats (figure 14.5). These repetitive regions can be within upstream regulatory elements or within the coding region themselves; typically these repeated regions are of low copy number. In each generation there is the potential for these repetitive sequences to expand, and the expansion will change gene expression.","{'57d4037c-af1a-4ef7-9399-4fba65103c73': 'Disorders in this category are caused by expansion of tandem trinucleotide repeats (figure 14.5). These repetitive regions can be within upstream regulatory elements or within the coding region themselves; typically these repeated regions are of low copy number. In each generation there is the potential for these repetitive sequences to expand, and the expansion will change gene expression.', '604dac48-3af5-40d1-bbaa-035508fca9b1': 'Triplicate repeat disorders are also characteristic of anticipation where the affected phenotype of individuals becomes progressively worse with each generation. Classic repeat disorders include Fragile X and Huntingtonʼs disease. In the case of Fragile X, the repeated region becomes hypermethylated and the methylation pattern expands into the promoter region for the gene. This will lead to silencing of the transcript. The gene itself, FMR1, is involved in mRNA splicing, and the loss of this gene product has a pleiotropic effect.', 'c31fb12a-2d98-4037-87f3-ac7c2f2d7503': '14.2 References and resources', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 14.3,cell_bio/images/Figure 14.3.jpg,Figure 14.3: Graphic representation of penetrance and expressivity.,"Penetrance refers to the display of any signs or symptoms if you have the genetic abnormality; this does not describe the variety of phenotype. As illustrated in figure 14.3, this refers to the number of “affected (purple)” versus “unaffected (white)” cells in an individual. Individuals with a greater number of purple cells may have a more pronounced phenotype than individuals with greater numbers of white cells.","{'87b0abcd-4cd2-4dc1-bf29-07cd4bfc994c': '17.2 Endocytosis', 'b44f6426-7f61-492a-bb25-cca17ef783dd': '14.2 Non-Mendelian Inheritance', 'd1296041-94c4-4749-95bb-7c5387f35ff5': 'The majority of genetic disorders are not inherited in a Mendelian fashion. Even in cases where Mendelian genetics can predict genotype, the disease phenotype may not be displayed or may be variable due to external influences. This section describes some additional factors that influence presentation and inheritance patterns.', '72b8404a-4a28-4f4c-bc41-c30c39a353fa': 'Penetrance refers to the display of any signs or symptoms if you have the genetic abnormality; this\xa0does not describe the variety of phenotype. As illustrated in figure 14.3, this refers to the number of “affected (purple)” versus “unaffected (white)” cells in an individual. Individuals with a greater number of purple cells may have a more pronounced phenotype than individuals with greater numbers of white cells.', '51306d88-d853-4baa-9cbf-2cdf55e39cb7': 'Variable phenotypes can present due to changes in expressivity or pleiotropy. These terms refer to the variety of presentations from a single genetic disorder\xa0(variable expression). As illustrated in figure 14.3, expressivity can be a range of “purplish”\xa0colors, which may give rise to a variable phenotype. In other more complicated genetic cases, both penetrance and expressivity must be considered when making a diagnosis. Pleiotropy of a disorder is best described as a single gene disorder having implications on several different organ systems.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 14.4,cell_bio/images/Figure 14.4.jpg,Figure 14.4: Mitochondrial inheritance pattern.,"Therefore in this inheritance modality, the females can transmit the trait to all offspring (figure 14.4), however, only female offspring will continue to transmit the disorder. Disease phenotype in mitochondrial disease is extremely variable due to mitochondrial heteroplasmy.","{'546505ca-2408-4d24-9d61-57a21542b1f5': 'Mitochondria are unique in that they have multiple copies of a circular chromosome. This DNA is independent of nuclear DNA and inherited from the mother.', 'f9a83560-60fd-4e80-a82d-7ac388c514fe': 'Therefore in this inheritance modality, the females can transmit the trait to all offspring (figure 14.4), however, only female offspring will continue to transmit the disorder. Disease phenotype in mitochondrial disease is extremely variable due to mitochondrial heteroplasmy.', '1e3f5a07-6c9c-4ed6-b7f4-ceaf8d97ab9f': 'Heteroplasmy is a term referring to the diversity of the mitochondrial genome within each cell. During cell division, mitochondria are divided randomly between the two daughter cells, and therefore the percentage of affected mitochondrial DNA (mtDNA) will also be variable within the offspring. The mitochondria generate energy for the rest of the cell, therefore disease transmitted through mitochondrial inheritance affects high-energy organs (this is a good example of pleiotropy).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 14.5,cell_bio/images/Figure 14.5.jpg,Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease.,"Disorders in this category are caused by expansion of tandem trinucleotide repeats (figure 14.5). These repetitive regions can be within upstream regulatory elements or within the coding region themselves; typically these repeated regions are of low copy number. In each generation there is the potential for these repetitive sequences to expand, and the expansion will change gene expression.","{'57d4037c-af1a-4ef7-9399-4fba65103c73': 'Disorders in this category are caused by expansion of tandem trinucleotide repeats (figure 14.5). These repetitive regions can be within upstream regulatory elements or within the coding region themselves; typically these repeated regions are of low copy number. In each generation there is the potential for these repetitive sequences to expand, and the expansion will change gene expression.', '604dac48-3af5-40d1-bbaa-035508fca9b1': 'Triplicate repeat disorders are also characteristic of anticipation where the affected phenotype of individuals becomes progressively worse with each generation. Classic repeat disorders include Fragile X and Huntingtonʼs disease. In the case of Fragile X, the repeated region becomes hypermethylated and the methylation pattern expands into the promoter region for the gene. This will lead to silencing of the transcript. The gene itself, FMR1, is involved in mRNA splicing, and the loss of this gene product has a pleiotropic effect.', 'c31fb12a-2d98-4037-87f3-ac7c2f2d7503': '14.2 References and resources', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 14.6,cell_bio/images/Figure 14.6.jpg,Figure 14.6: Relationship between centimorgans and recombination frequency.,"A very small linkage distance means the traits are rarely separated during meiosis. A distance of 0 cM means two traits always stay together, implying that they are extremely close to one another on the same chromosome. If the two traits separate from one another 1 percent of the time during meiosis, they are described as being 1 cM apart; if the two traits separate from one another 5 percent of the time during meiosis, they are described as being 5 cM apart (figure 14.6).","{'89c2199d-7df6-47ef-a661-a2adb655b9a1': 'Syntenic genes may become detached from one another through crossing over (or recombination). For large chromosomes, crossing over is so common that genes at opposite ends of the chromosome are inherited together no more often than if they resided on entirely different chromosomes.', '5ecb5062-be21-47b6-857f-d4b88861b38e': 'When markers are close enough together on the same chromosome, crossing over fails to separate them frequently enough for them to be inherited independently of one another. This is evidenced by coinheritance of greater than 50 percent.', '441daa8d-be56-4ad8-960a-cec991558edd': 'The unit of measure in linkage studies is “centimorgans.” This concept can be confusing because we refer to the “distance” between two traits, but what is measured experimentally is the frequency of coinheritance, not physical distance.', '33a2d8ce-42e5-401e-bca6-076592f8a368': 'A very small linkage distance means the traits are rarely separated during meiosis. A distance of 0 cM means two traits always stay together, implying that they are extremely close to one another on the same chromosome. If the two traits separate from one another 1 percent\xa0of the time during meiosis, they are described as being 1 cM apart; if the two traits separate from one another 5 percent\xa0of the time during meiosis, they are described as being 5 cM apart (figure 14.6).', '5da29400-62c9-43ee-99de-bf2751172856': 'The further apart two genes or markers are on the same chromosome increases the probability of a crossover occurring in between the two markers. Studies to determine linkage require the careful study of large numbers of parents and their offspring. Careful study of the family relationships across three generations allows linkage phases to be determined. In this case, the grandparents’ information is required to determine how the genes are initially linked in the parents, and the grandchildren are studied to determine recombination events (crossing over) that separate the genes or markers during meiosis in the parents.', 'b8187711-490a-45ba-a3cf-7731c045b8b9': 'Distance can be expressed in cM as described previously, or in terms of theta (θ), which are proportions. Remember, both are measures of probability, not physical distance. Linkage determinations are based on the fundamental rules of probability and binomial mathematics. Like any probability issue, a ratio greater than one reflects odds in favor (of linkage), and less than one reflects odds against.', 'eed374b7-d783-4045-bbc6-0ffdad5c9b2e': 'For linkage studies, each family represents an independent estimate of the odds in favor of (or against) linkage. The property within standard probability laws is the concept of joint probability. To determine joint probability, meaning the chance that BOTH of two events will happen, we use what is often called the “AND rule.”\xa0The AND rule applies whenever the probabilities under study are independent of one another.', 'eaa4b884-d485-4c10-afae-822e67f1001f': 'Multiplying the results of many families is challenging, and was particularly so before computer resources became readily available. It is simpler mathematically to add numbers. We can move from multiplication to addition if we simply use the log of the probability instead of the probability number itself. Remember that the log of a number that is less than one is a negative number, and for a number greater than one, it is a positive number. Using a log conversion makes it simple to see if the ratio of the odds is favorable (positive) or unfavorable. The term\xa0“LOD score” refers to the log (base 10) of the odds of linkage, looking across a series of independent families.', 'f5c3e44c-0c83-4bd9-9869-0e01002b6dae': 'There really are just two things to remember about LOD scores:', '9c1873bc-3395-4547-b81a-5b39d92e3ba3': 'Population association is easily confused with the concepts surrounding linkage. These studies look for a statistical association between a marker (often a single nucleotide polymorphism or SNP) and a specific trait. The concept of population association can be exploited to simultaneously study a very large number of detectable genetic markers (SNPs) in patient populations with common disorders.', 'df1d7f5b-d4d7-4aaf-8505-da6577a48c60': 'Much of the power of personalized medicine is derived from such associations. There is an abundance of GWAS\xa0that appear in the medical literature. This is a highly sophisticated type of case-control study for which careful study design is required to avoid spurious findings. These studies provide information related to common genetic traits but do not help address genetic manifestations of rare traits in a population (figure 14.7).', '83e189a5-b5d6-4da4-bb74-07a26297c2a7': 'For more information on these types of studies, please see: https://www.genome.gov/20019523/geno…ies-factsheet/.', '63a5e78c-76a1-4e96-b119-9cdc3c5b8fda': '14.3 References and resources', 'b06b4521-aa76-4a66-b570-f70cbc33f515': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 12: Mendel’s Experiments and Heridity, Chapter 13: Modern Understandings of Inheritance.', '741677e2-4c96-4098-b38e-8272afbca11e': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 55–59.', 'cebc5bd4-7375-4f54-8976-63606b77d14d': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson.\xa0Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 7: Patterns of Single Gene Inheritance, Chapter 9: Genetic Variations in Populations, Chapter 10: Identifying the Genetic Basis for Human Disease.'}"
Figure 14.7,cell_bio/images/Figure 14.7.jpg,Figure 14.7: Schematic of GWAS.,Much of the power of personalized medicine is derived from such associations. There is an abundance of GWAS that appear in the medical literature. This is a highly sophisticated type of case-control study for which careful study design is required to avoid spurious findings. These studies provide information related to common genetic traits but do not help address genetic manifestations of rare traits in a population (figure 14.7).,"{'9c1873bc-3395-4547-b81a-5b39d92e3ba3': 'Population association is easily confused with the concepts surrounding linkage. These studies look for a statistical association between a marker (often a single nucleotide polymorphism or SNP) and a specific trait. The concept of population association can be exploited to simultaneously study a very large number of detectable genetic markers (SNPs) in patient populations with common disorders.', 'df1d7f5b-d4d7-4aaf-8505-da6577a48c60': 'Much of the power of personalized medicine is derived from such associations. There is an abundance of GWAS\xa0that appear in the medical literature. This is a highly sophisticated type of case-control study for which careful study design is required to avoid spurious findings. These studies provide information related to common genetic traits but do not help address genetic manifestations of rare traits in a population (figure 14.7).', '83e189a5-b5d6-4da4-bb74-07a26297c2a7': 'For more information on these types of studies, please see: https://www.genome.gov/20019523/geno…ies-factsheet/.', '63a5e78c-76a1-4e96-b119-9cdc3c5b8fda': '14.3 References and resources', 'b06b4521-aa76-4a66-b570-f70cbc33f515': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 12: Mendel’s Experiments and Heridity, Chapter 13: Modern Understandings of Inheritance.', '741677e2-4c96-4098-b38e-8272afbca11e': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 55–59.', 'cebc5bd4-7375-4f54-8976-63606b77d14d': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson.\xa0Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 7: Patterns of Single Gene Inheritance, Chapter 9: Genetic Variations in Populations, Chapter 10: Identifying the Genetic Basis for Human Disease.'}"
Figure 14.6,cell_bio/images/Figure 14.6.jpg,Figure 14.6: Relationship between centimorgans and recombination frequency.,"A very small linkage distance means the traits are rarely separated during meiosis. A distance of 0 cM means two traits always stay together, implying that they are extremely close to one another on the same chromosome. If the two traits separate from one another 1 percent of the time during meiosis, they are described as being 1 cM apart; if the two traits separate from one another 5 percent of the time during meiosis, they are described as being 5 cM apart (figure 14.6).","{'89c2199d-7df6-47ef-a661-a2adb655b9a1': 'Syntenic genes may become detached from one another through crossing over (or recombination). For large chromosomes, crossing over is so common that genes at opposite ends of the chromosome are inherited together no more often than if they resided on entirely different chromosomes.', '5ecb5062-be21-47b6-857f-d4b88861b38e': 'When markers are close enough together on the same chromosome, crossing over fails to separate them frequently enough for them to be inherited independently of one another. This is evidenced by coinheritance of greater than 50 percent.', '441daa8d-be56-4ad8-960a-cec991558edd': 'The unit of measure in linkage studies is “centimorgans.” This concept can be confusing because we refer to the “distance” between two traits, but what is measured experimentally is the frequency of coinheritance, not physical distance.', '33a2d8ce-42e5-401e-bca6-076592f8a368': 'A very small linkage distance means the traits are rarely separated during meiosis. A distance of 0 cM means two traits always stay together, implying that they are extremely close to one another on the same chromosome. If the two traits separate from one another 1 percent\xa0of the time during meiosis, they are described as being 1 cM apart; if the two traits separate from one another 5 percent\xa0of the time during meiosis, they are described as being 5 cM apart (figure 14.6).', '5da29400-62c9-43ee-99de-bf2751172856': 'The further apart two genes or markers are on the same chromosome increases the probability of a crossover occurring in between the two markers. Studies to determine linkage require the careful study of large numbers of parents and their offspring. Careful study of the family relationships across three generations allows linkage phases to be determined. In this case, the grandparents’ information is required to determine how the genes are initially linked in the parents, and the grandchildren are studied to determine recombination events (crossing over) that separate the genes or markers during meiosis in the parents.', 'b8187711-490a-45ba-a3cf-7731c045b8b9': 'Distance can be expressed in cM as described previously, or in terms of theta (θ), which are proportions. Remember, both are measures of probability, not physical distance. Linkage determinations are based on the fundamental rules of probability and binomial mathematics. Like any probability issue, a ratio greater than one reflects odds in favor (of linkage), and less than one reflects odds against.', 'eed374b7-d783-4045-bbc6-0ffdad5c9b2e': 'For linkage studies, each family represents an independent estimate of the odds in favor of (or against) linkage. The property within standard probability laws is the concept of joint probability. To determine joint probability, meaning the chance that BOTH of two events will happen, we use what is often called the “AND rule.”\xa0The AND rule applies whenever the probabilities under study are independent of one another.', 'eaa4b884-d485-4c10-afae-822e67f1001f': 'Multiplying the results of many families is challenging, and was particularly so before computer resources became readily available. It is simpler mathematically to add numbers. We can move from multiplication to addition if we simply use the log of the probability instead of the probability number itself. Remember that the log of a number that is less than one is a negative number, and for a number greater than one, it is a positive number. Using a log conversion makes it simple to see if the ratio of the odds is favorable (positive) or unfavorable. The term\xa0“LOD score” refers to the log (base 10) of the odds of linkage, looking across a series of independent families.', 'f5c3e44c-0c83-4bd9-9869-0e01002b6dae': 'There really are just two things to remember about LOD scores:', '9c1873bc-3395-4547-b81a-5b39d92e3ba3': 'Population association is easily confused with the concepts surrounding linkage. These studies look for a statistical association between a marker (often a single nucleotide polymorphism or SNP) and a specific trait. The concept of population association can be exploited to simultaneously study a very large number of detectable genetic markers (SNPs) in patient populations with common disorders.', 'df1d7f5b-d4d7-4aaf-8505-da6577a48c60': 'Much of the power of personalized medicine is derived from such associations. There is an abundance of GWAS\xa0that appear in the medical literature. This is a highly sophisticated type of case-control study for which careful study design is required to avoid spurious findings. These studies provide information related to common genetic traits but do not help address genetic manifestations of rare traits in a population (figure 14.7).', '83e189a5-b5d6-4da4-bb74-07a26297c2a7': 'For more information on these types of studies, please see: https://www.genome.gov/20019523/geno…ies-factsheet/.', '63a5e78c-76a1-4e96-b119-9cdc3c5b8fda': '14.3 References and resources', 'b06b4521-aa76-4a66-b570-f70cbc33f515': 'Clark, M. A.\xa0Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 12: Mendel’s Experiments and Heridity, Chapter 13: Modern Understandings of Inheritance.', '741677e2-4c96-4098-b38e-8272afbca11e': 'Le, T., and V. Bhushan.\xa0First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 55–59.', 'cebc5bd4-7375-4f54-8976-63606b77d14d': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson.\xa0Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 7: Patterns of Single Gene Inheritance, Chapter 9: Genetic Variations in Populations, Chapter 10: Identifying the Genetic Basis for Human Disease.'}"
Figure 13.1,cell_bio/images/Figure 13.1.jpg,Figure 13.1: Representative karyotype illustrating twenty-two pairs of autosomes and one pair of sex chromosomes.,"Chromosomes can be analyzed from living tissue and arranged in a karyotype (figure 13.1). Chromosomes can be sorted into the autosomal pairs (twenty-two) and sex chromosomes and classified to determine any abnormalities. A normal karyotype for a female is 46,XX, and a male is 46,XY. Deviations from this patterning can result in chromosomal abnormalities, which may or may not produce viable offspring.","{'bad8f8d1-1d3a-43e7-8392-5213c3c48a96': 'Chromosomes can be analyzed from living tissue and arranged in a karyotype (figure 13.1). Chromosomes can be sorted into the autosomal pairs (twenty-two) and sex chromosomes and classified to determine any abnormalities. A normal karyotype for a female is 46,XX, and a male is 46,XY. Deviations from this patterning can result in chromosomal abnormalities, which may or may not produce viable offspring.', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.2,cell_bio/images/Figure 13.2.jpg,Figure 13.2: Basics of chromosome structure.,"Each chromosome is made up of a p and q arm held together by the centromere. The position of the centromere is a distinguishing characteristic and can be classified as metacentric, submetacentric, or acrocentric. The position of the centromere plays a key role in mitotic and meiotic division as chromosomes with skewed centromeres are more likely to be involved in nondisjunction events (figure 13.2).","{'b42eb673-ec33-42c6-8265-56b815cbc845': 'Each chromosome is made up of a p and q arm held together by the centromere. The position of the centromere is a distinguishing characteristic and can be classified as metacentric, submetacentric, or acrocentric. The position of the centromere plays a key role in mitotic and meiotic division as chromosomes with skewed centromeres are more likely to be involved in nondisjunction events (figure 13.2).', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.3,cell_bio/images/Figure 13.3.jpg,Figure 13.3: Summary of meiotic and mitotic cell divisions.,"The precise pairing and segregation during the two meiotic divisions ensures the equal division of the somatic diploid set of chromosomes into the four resulting haploid cells (figure 13.3). Nondisjunction is the term used when the two homologous chromosomes in the first division or the two sister chromatids in the second do not segregate from each other at anaphase, but instead move together into the same daughter cell. This term may also be used for the same occurrence in mitotic cell divisions when the sister chromatids fail to segregate properly.","{'2d57684c-1779-483e-9269-0ab2600660c9': 'The precise pairing and segregation during the two meiotic divisions ensures the equal division of the somatic diploid set of chromosomes into the four resulting haploid cells (figure 13.3). Nondisjunction is the term used when the two homologous chromosomes in the first division or the two sister chromatids in the second do not segregate from each other at anaphase, but instead move together into the same daughter cell. This term may also be used for the same occurrence in mitotic cell divisions when the sister chromatids fail to segregate properly.', '6be9bb20-9108-413d-a2d4-035d2d8e2402': 'Table 13.1: Summary of meiotic and mitotic cell divisions.', '0f8aaaa5-0a19-4cd6-bd72-8171aba3d86d': 'These nondisjunction events can result in unequal distribution of chromosomes rendering a cell with an atypical chromosome number. A cell that is euploid would contain all twenty-three\xa0chromosomes, while polyploidy would suggest additional chromosomes within the cell. In humans, aneuploidy of autosomes are the most clinically important abnormalities to address, and the most common cause of this is a nondisjunction event.', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.4,cell_bio/images/Figure 13.4.jpg,Figure 13.4: Comparison of nondisjunction in meiosis I versus meiosis II.,Chromosomal trisomies caused by nondisjunction at meiosis I can be distinguished from those occurring at meiosis II by examining the inheritance patterns of polymorphic markers near the centromere in cells obtained from the trisomic offspring (figure 13.4).,"{'4b2ca528-0100-41c6-8698-cd784fcbcfa2': 'Normally, one copy of each chromosome is inherited from each parent; however, when there is nondisjunction at either anaphase I or anaphase II, gametes will contain either two copies or no copies of the chromosome, which failed to disjoin. At fertilization, when the gamete provided by the other parent contributes one copy of each chromosome, the newly formed zygote will instead possess three copies (trisomy) or one copy (monosomy) of the chromosome, which failed to disjoin. Trisomy and monosomy are both examples of aneuploidy, a general term that\xa0denotes an abnormality in the number of copies of any given chromosome.', '1e1cdff8-54c0-4be4-833a-c7ad36c277e6': 'Chromosomal trisomies caused by nondisjunction at meiosis I can be distinguished from those occurring at meiosis II by examining the inheritance patterns of polymorphic markers near the centromere in cells obtained from the trisomic offspring (figure 13.4).', 'a3566fc6-cd1f-40f3-838b-b641923dd82d': 'Meiotic nondisjunction is the cause of the most common and clinically significant class of chromosomal abnormalities. This is true for chromosomal abnormalities found in spontaneous abortions where approximately 35 percent\xa0of miscarriages have a trisomy or monosomy, in stillbirths with approximately 4 percent\xa0being aneuploid, and also in live births with 0.3 percent\xa0being affected. Most autosomal trisomies and virtually all autosomal monosomies result in pregnancy failure or spontaneous abortion. Trisomies for chromosomes 13, 18, or 21 can result in the live birth of an infant with birth defects and intellectual disability. Extra copies of the X or Y chromosome are compatible with live birth, as is a small fraction of the conceptions with only a single X chromosome (Turner syndrome).', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.5,cell_bio/images/Figure 13.5.jpg,Figure 13.5: Mosaicism resulting in cells with differing genetics across the body.,"Mitotic nondisjunction occurs after zygote formation and may be the result of misdivision of a cell after a normal conception with gain (or loss) of a chromosome during embryogenesis. This typically results in mosaicism (figure 13.5), the presence of multiple and genetically distinct cell populations in the same individual. The timing of mitotic nondisjunction events determines the ratio of aneuploid to normal cells and the types of tissues affected. For example, if the nondisjunction occurs early in development, the majority of cells and tissues would carry this aneuploidy, which would result in an increased clinical severity.","{'d8c269d1-8e17-4d82-bbb3-40dd31c2b2b5': 'Mitotic nondisjunction occurs after zygote formation and may be the result of misdivision of a cell after a normal conception with gain (or loss) of a chromosome during embryogenesis. This typically results in mosaicism (figure 13.5), the presence of multiple and genetically distinct cell populations in the same individual. The timing of mitotic nondisjunction events determines the ratio of aneuploid to normal cells and the types of tissues affected. For example, if the nondisjunction occurs early in development, the majority of cells and tissues would carry this aneuploidy, which would result in an increased clinical severity.', '804205fc-eb30-43f4-a400-a40a5f8ab05e': 'Mosaicism is often found in sex chromosome abnormalities and some autosomal trisomies. Over half of mosaic trisomy 21 cases have been shown to be the result of loss of the extra 21 in subsequent mitotic divisions after a trisomic conception, while trisomy 8 mosaicism typically seems to be acquired during mitotic divisions after a normal conception.', '23884c1c-f607-4784-b779-b3004ef05ad7': 'Chimaerism is similar to mosaicism in that multiple, genetically distinct cell lines are present in the same individual. Here, however, the cell lines begin as different zygotes rather than arising through changes during mitosis. This can arise naturally from the fusion of closely implanted twins or migration of cells between embryos in multiple gestations, or it can be caused by the transplantation of tissues or organs from donors for medical treatment.', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.6,cell_bio/images/Figure 13.6.jpg,Figure 13.6: Genetic basis of Prader-Willi syndrome (PWS) and Angelman syndrome (AS). UPD: Uniparental disomy; Square: imprinting on the maternal allele.,"An example of this is Prader-Willi syndrome, a rare disorder due to the deletion or loss of expression from the paternal chromosome 15. This short region of genes is subject to maternal imprinting and typically only expressed from a single chromosomal loci. In these individuals, loss of expressivity from the paternal allele (either through a microdeletion or loss of chromosome 15) and imprinting of the maternal allele leads to this presentation. If both copies of the region are inherited from the paternal allele the result is the presentation of Angelman syndrome (figure 13.6).","{'779f1f86-7f82-4769-b64d-190de0a10fa3': 'A deletion occurs when a chromosome breaks at two sites and the segment between them gets lost. Depending on the size and breakage site, varying numbers of genes can be lost. In rare cases the deletions are large enough to be visible under the light microscope. Smaller deletions have traditionally been identified by molecular cytogenetic (FISH) analyses, although they are now routinely detected with chromosome oligonucleotide arrays. These are called microdeletions, while the resulting pathologies are called microdeletion syndromes.', 'ee2c0108-b8a6-4f02-b5cb-4c88126d99b5': 'An example of this is Prader-Willi syndrome, a rare disorder due to the deletion or loss of expression from the paternal chromosome 15. This short region of genes is subject to maternal imprinting and typically only expressed from a single chromosomal loci. In these individuals, loss of expressivity from the paternal allele (either through a microdeletion or loss of chromosome 15) and imprinting of the maternal allele leads to this presentation. If both copies of the region are inherited from the paternal allele the result is the presentation of Angelman syndrome (figure 13.6).', '6def6267-8e27-42a2-aa58-2f147743b535': 'Duplications refer to a chromosome segment appearing in two (often sequentially inserted) copies on a single homolog. Most of the time, this is caused by a nonhomologous recombination in the first meiotic division.', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.7,cell_bio/images/Figure 13.7.jpg,Figure 13.7: Example of a chromosome inversion and translocation.,"Inversion occurs when a chromosome segment between two breaks is rotated 180 degrees before reinsertion. The gene copy number remains the same; clinical symptoms may arise if there is an additional deletion or duplication, if the breaks occur within the coding region of a gene, or if the regulation of a gene is altered. Like other balanced chromosomal aberrations, inversions may cause infertility, recurrent miscarriages, or an unbalanced chromosome complement in a child (figure 13.7).","{'c5d22359-57cb-4792-a8fd-cfeed7b0aaf5': 'Inversion occurs when a chromosome segment between two breaks is rotated 180 degrees before reinsertion. The gene copy number remains the same; clinical symptoms may arise if there is an additional deletion or duplication, if the breaks occur within the coding region of a gene, or if the regulation of a gene is altered. Like other balanced chromosomal aberrations, inversions may cause infertility, recurrent miscarriages, or an unbalanced chromosome complement in a child (figure 13.7).', '44554f7d-4769-457e-8dc3-92de782d954c': 'Translocations occur most often during meiosis if unequal crossing over occurs. Additionally, translocations (interchange of genetic material between nonhomologous chromosomes) can be another source of chromosomal abnormality (figure 13.7).', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.7,cell_bio/images/Figure 13.7.jpg,Figure 13.7: Example of a chromosome inversion and translocation.,"Inversion occurs when a chromosome segment between two breaks is rotated 180 degrees before reinsertion. The gene copy number remains the same; clinical symptoms may arise if there is an additional deletion or duplication, if the breaks occur within the coding region of a gene, or if the regulation of a gene is altered. Like other balanced chromosomal aberrations, inversions may cause infertility, recurrent miscarriages, or an unbalanced chromosome complement in a child (figure 13.7).","{'c5d22359-57cb-4792-a8fd-cfeed7b0aaf5': 'Inversion occurs when a chromosome segment between two breaks is rotated 180 degrees before reinsertion. The gene copy number remains the same; clinical symptoms may arise if there is an additional deletion or duplication, if the breaks occur within the coding region of a gene, or if the regulation of a gene is altered. Like other balanced chromosomal aberrations, inversions may cause infertility, recurrent miscarriages, or an unbalanced chromosome complement in a child (figure 13.7).', '44554f7d-4769-457e-8dc3-92de782d954c': 'Translocations occur most often during meiosis if unequal crossing over occurs. Additionally, translocations (interchange of genetic material between nonhomologous chromosomes) can be another source of chromosomal abnormality (figure 13.7).', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.1,cell_bio/images/Figure 13.1.jpg,Figure 13.1: Representative karyotype illustrating twenty-two pairs of autosomes and one pair of sex chromosomes.,"Chromosomes can be analyzed from living tissue and arranged in a karyotype (figure 13.1). Chromosomes can be sorted into the autosomal pairs (twenty-two) and sex chromosomes and classified to determine any abnormalities. A normal karyotype for a female is 46,XX, and a male is 46,XY. Deviations from this patterning can result in chromosomal abnormalities, which may or may not produce viable offspring.","{'bad8f8d1-1d3a-43e7-8392-5213c3c48a96': 'Chromosomes can be analyzed from living tissue and arranged in a karyotype (figure 13.1). Chromosomes can be sorted into the autosomal pairs (twenty-two) and sex chromosomes and classified to determine any abnormalities. A normal karyotype for a female is 46,XX, and a male is 46,XY. Deviations from this patterning can result in chromosomal abnormalities, which may or may not produce viable offspring.', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.6,cell_bio/images/Figure 13.6.jpg,Figure 13.6: Genetic basis of Prader-Willi syndrome (PWS) and Angelman syndrome (AS). UPD: Uniparental disomy; Square: imprinting on the maternal allele.,"An example of this is Prader-Willi syndrome, a rare disorder due to the deletion or loss of expression from the paternal chromosome 15. This short region of genes is subject to maternal imprinting and typically only expressed from a single chromosomal loci. In these individuals, loss of expressivity from the paternal allele (either through a microdeletion or loss of chromosome 15) and imprinting of the maternal allele leads to this presentation. If both copies of the region are inherited from the paternal allele the result is the presentation of Angelman syndrome (figure 13.6).","{'779f1f86-7f82-4769-b64d-190de0a10fa3': 'A deletion occurs when a chromosome breaks at two sites and the segment between them gets lost. Depending on the size and breakage site, varying numbers of genes can be lost. In rare cases the deletions are large enough to be visible under the light microscope. Smaller deletions have traditionally been identified by molecular cytogenetic (FISH) analyses, although they are now routinely detected with chromosome oligonucleotide arrays. These are called microdeletions, while the resulting pathologies are called microdeletion syndromes.', 'ee2c0108-b8a6-4f02-b5cb-4c88126d99b5': 'An example of this is Prader-Willi syndrome, a rare disorder due to the deletion or loss of expression from the paternal chromosome 15. This short region of genes is subject to maternal imprinting and typically only expressed from a single chromosomal loci. In these individuals, loss of expressivity from the paternal allele (either through a microdeletion or loss of chromosome 15) and imprinting of the maternal allele leads to this presentation. If both copies of the region are inherited from the paternal allele the result is the presentation of Angelman syndrome (figure 13.6).', '6def6267-8e27-42a2-aa58-2f147743b535': 'Duplications refer to a chromosome segment appearing in two (often sequentially inserted) copies on a single homolog. Most of the time, this is caused by a nonhomologous recombination in the first meiotic division.', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.2,cell_bio/images/Figure 13.2.jpg,Figure 13.2: Basics of chromosome structure.,"Each chromosome is made up of a p and q arm held together by the centromere. The position of the centromere is a distinguishing characteristic and can be classified as metacentric, submetacentric, or acrocentric. The position of the centromere plays a key role in mitotic and meiotic division as chromosomes with skewed centromeres are more likely to be involved in nondisjunction events (figure 13.2).","{'b42eb673-ec33-42c6-8265-56b815cbc845': 'Each chromosome is made up of a p and q arm held together by the centromere. The position of the centromere is a distinguishing characteristic and can be classified as metacentric, submetacentric, or acrocentric. The position of the centromere plays a key role in mitotic and meiotic division as chromosomes with skewed centromeres are more likely to be involved in nondisjunction events (figure 13.2).', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.3,cell_bio/images/Figure 13.3.jpg,Figure 13.3: Summary of meiotic and mitotic cell divisions.,"The precise pairing and segregation during the two meiotic divisions ensures the equal division of the somatic diploid set of chromosomes into the four resulting haploid cells (figure 13.3). Nondisjunction is the term used when the two homologous chromosomes in the first division or the two sister chromatids in the second do not segregate from each other at anaphase, but instead move together into the same daughter cell. This term may also be used for the same occurrence in mitotic cell divisions when the sister chromatids fail to segregate properly.","{'2d57684c-1779-483e-9269-0ab2600660c9': 'The precise pairing and segregation during the two meiotic divisions ensures the equal division of the somatic diploid set of chromosomes into the four resulting haploid cells (figure 13.3). Nondisjunction is the term used when the two homologous chromosomes in the first division or the two sister chromatids in the second do not segregate from each other at anaphase, but instead move together into the same daughter cell. This term may also be used for the same occurrence in mitotic cell divisions when the sister chromatids fail to segregate properly.', '6be9bb20-9108-413d-a2d4-035d2d8e2402': 'Table 13.1: Summary of meiotic and mitotic cell divisions.', '0f8aaaa5-0a19-4cd6-bd72-8171aba3d86d': 'These nondisjunction events can result in unequal distribution of chromosomes rendering a cell with an atypical chromosome number. A cell that is euploid would contain all twenty-three\xa0chromosomes, while polyploidy would suggest additional chromosomes within the cell. In humans, aneuploidy of autosomes are the most clinically important abnormalities to address, and the most common cause of this is a nondisjunction event.', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.4,cell_bio/images/Figure 13.4.jpg,Figure 13.4: Comparison of nondisjunction in meiosis I versus meiosis II.,Chromosomal trisomies caused by nondisjunction at meiosis I can be distinguished from those occurring at meiosis II by examining the inheritance patterns of polymorphic markers near the centromere in cells obtained from the trisomic offspring (figure 13.4).,"{'4b2ca528-0100-41c6-8698-cd784fcbcfa2': 'Normally, one copy of each chromosome is inherited from each parent; however, when there is nondisjunction at either anaphase I or anaphase II, gametes will contain either two copies or no copies of the chromosome, which failed to disjoin. At fertilization, when the gamete provided by the other parent contributes one copy of each chromosome, the newly formed zygote will instead possess three copies (trisomy) or one copy (monosomy) of the chromosome, which failed to disjoin. Trisomy and monosomy are both examples of aneuploidy, a general term that\xa0denotes an abnormality in the number of copies of any given chromosome.', '1e1cdff8-54c0-4be4-833a-c7ad36c277e6': 'Chromosomal trisomies caused by nondisjunction at meiosis I can be distinguished from those occurring at meiosis II by examining the inheritance patterns of polymorphic markers near the centromere in cells obtained from the trisomic offspring (figure 13.4).', 'a3566fc6-cd1f-40f3-838b-b641923dd82d': 'Meiotic nondisjunction is the cause of the most common and clinically significant class of chromosomal abnormalities. This is true for chromosomal abnormalities found in spontaneous abortions where approximately 35 percent\xa0of miscarriages have a trisomy or monosomy, in stillbirths with approximately 4 percent\xa0being aneuploid, and also in live births with 0.3 percent\xa0being affected. Most autosomal trisomies and virtually all autosomal monosomies result in pregnancy failure or spontaneous abortion. Trisomies for chromosomes 13, 18, or 21 can result in the live birth of an infant with birth defects and intellectual disability. Extra copies of the X or Y chromosome are compatible with live birth, as is a small fraction of the conceptions with only a single X chromosome (Turner syndrome).', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.5,cell_bio/images/Figure 13.5.jpg,Figure 13.5: Mosaicism resulting in cells with differing genetics across the body.,"Mitotic nondisjunction occurs after zygote formation and may be the result of misdivision of a cell after a normal conception with gain (or loss) of a chromosome during embryogenesis. This typically results in mosaicism (figure 13.5), the presence of multiple and genetically distinct cell populations in the same individual. The timing of mitotic nondisjunction events determines the ratio of aneuploid to normal cells and the types of tissues affected. For example, if the nondisjunction occurs early in development, the majority of cells and tissues would carry this aneuploidy, which would result in an increased clinical severity.","{'d8c269d1-8e17-4d82-bbb3-40dd31c2b2b5': 'Mitotic nondisjunction occurs after zygote formation and may be the result of misdivision of a cell after a normal conception with gain (or loss) of a chromosome during embryogenesis. This typically results in mosaicism (figure 13.5), the presence of multiple and genetically distinct cell populations in the same individual. The timing of mitotic nondisjunction events determines the ratio of aneuploid to normal cells and the types of tissues affected. For example, if the nondisjunction occurs early in development, the majority of cells and tissues would carry this aneuploidy, which would result in an increased clinical severity.', '804205fc-eb30-43f4-a400-a40a5f8ab05e': 'Mosaicism is often found in sex chromosome abnormalities and some autosomal trisomies. Over half of mosaic trisomy 21 cases have been shown to be the result of loss of the extra 21 in subsequent mitotic divisions after a trisomic conception, while trisomy 8 mosaicism typically seems to be acquired during mitotic divisions after a normal conception.', '23884c1c-f607-4784-b779-b3004ef05ad7': 'Chimaerism is similar to mosaicism in that multiple, genetically distinct cell lines are present in the same individual. Here, however, the cell lines begin as different zygotes rather than arising through changes during mitosis. This can arise naturally from the fusion of closely implanted twins or migration of cells between embryos in multiple gestations, or it can be caused by the transplantation of tissues or organs from donors for medical treatment.', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.7,cell_bio/images/Figure 13.7.jpg,Figure 13.7: Example of a chromosome inversion and translocation.,"Inversion occurs when a chromosome segment between two breaks is rotated 180 degrees before reinsertion. The gene copy number remains the same; clinical symptoms may arise if there is an additional deletion or duplication, if the breaks occur within the coding region of a gene, or if the regulation of a gene is altered. Like other balanced chromosomal aberrations, inversions may cause infertility, recurrent miscarriages, or an unbalanced chromosome complement in a child (figure 13.7).","{'c5d22359-57cb-4792-a8fd-cfeed7b0aaf5': 'Inversion occurs when a chromosome segment between two breaks is rotated 180 degrees before reinsertion. The gene copy number remains the same; clinical symptoms may arise if there is an additional deletion or duplication, if the breaks occur within the coding region of a gene, or if the regulation of a gene is altered. Like other balanced chromosomal aberrations, inversions may cause infertility, recurrent miscarriages, or an unbalanced chromosome complement in a child (figure 13.7).', '44554f7d-4769-457e-8dc3-92de782d954c': 'Translocations occur most often during meiosis if unequal crossing over occurs. Additionally, translocations (interchange of genetic material between nonhomologous chromosomes) can be another source of chromosomal abnormality (figure 13.7).', '8e82a25e-74d4-4412-9ceb-6e3569561d0c': '13.1 References and resources', '5ce52b21-1270-4f00-a2a4-2a16f2b7bb00': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 13: Modern Understandings of Inheritance, Chapter 17: Biotechnology and Genomics.', 'b7b4a880-4845-42d0-a220-1384df7b9d95': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 52–55.', 'bea9c47f-2d76-4b3e-9b7f-9c8f9827d769': 'LeClair, R. J., and R. G. Best. “Chromosome Mechanics.” eLS (2016): 1–11. https://onlinelibrary.wiley.com/doi/….a0001441.pub3.', 'f472d67b-810e-4501-a8e1-16942e5f20d5': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 5: Principles of Clinical Cytogenetics.', '7029f490-3116-4d36-8cae-e27197201056': 'Csink AK, Henikoff S. Figure 13.6 Genetic basis of Prader-Willi (PWS) and Angelman syndrome(AS). Adapted under Fair Use from Trends in Genetics. Volume 14, Issue 5, 1 May 1998, pp 194-200. Figure 2. Prader-Willi and Angelman syndromes.', 'db853414-a1db-4f7c-9168-ffd4d2aaeb7c': '13.2 Biotechnology'}"
Figure 13.8,cell_bio/images/Figure 13.8.jpg,Figure 13.8: Basic process for DNA extraction.,"To study or manipulate nucleic acids, one must first isolate or extract the DNA or RNA from the cells. Most nucleic acid extraction techniques involve steps to break open the cell and use enzymatic reactions to destroy all macromolecules that are not desired. Enzymes such as proteases that break down proteins inactivate macromolecules, and ribonucleases (RNAses) that break down RNA are inhibited to ensure sample stability. Using alcohol precipitates the DNA. Human genomic DNA is usually visible as a gelatinous, white mass. One can store the DNA samples frozen at ‒80°C for several years (figure 13.8).","{'dfe65351-1ba7-4fa8-960e-e44770fe1482': 'To study or manipulate nucleic acids, one must first isolate or extract the DNA or RNA from the cells. Most nucleic acid extraction techniques involve steps to break open the cell and use enzymatic reactions to destroy all macromolecules that are not desired. Enzymes such as proteases that break down proteins inactivate macromolecules, and ribonucleases (RNAses) that break down RNA are inhibited to ensure sample stability. Using alcohol precipitates the DNA. Human genomic DNA is usually visible as a gelatinous, white mass. One can store the DNA samples frozen at ‒80°C for several years (figure 13.8).', '39d4cfc6-ce04-47b5-98c5-d4c1ab14badd': 'Different types of electrophoresis can be used to look at various changes at the level of the DNA (genome), RNA (transcriptome), or protein (proteome). In all cases, a sample (DNA, RNA, protein) is run on a gel (electrophoresis) and is then examined using a probe specific to the sample.', '4acfe7ef-a0ad-4d50-b52c-c791e0319240': 'Southern blots are designed to examine changes in DNA. DNA, typically genomic DNA, is probed with a DNA probe complementary to the region of interest in the genome (figure 13.12).', '571d2bed-0971-44cb-a251-73c8cd57b305': 'Northern blots are designed to examine changes in RNA. RNA is probed with a DNA probe complementary to the transcript of interest. This will detect changes in gene expression.', '031a0f8f-c5e9-4c3c-9765-046de41e93f2': 'Western blots are designed to examine changes in protein size and amount. Cell lysates or protein isolates are probed with an antibody specific to the protein of interest. This will detect changes in protein expression.', 'd549bc4e-7163-4272-9347-ceb25f5ae2e0': '13.2 References and resources', '19b8358b-71ca-4e78-8147-e5e8b16a93f5': 'Lieberman M, Peet A. Figure 13.11 Overview of polymerase chain reaction. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 329. Figure 17.10 Polymerase chain reaction (PCR). 2017.', '455d3428-bedc-45f5-9469-ad3db59bacba': 'National Cancer Institute. Figure 13.9 Male karyotype with G-banding patterns. Karyotype (normal). Public domain. From Wikimedia Commons.', '33f8d57d-33e6-4e6d-8074-027b7d7b4364': 'Some genes (the so-called “house-keeping genes”) are likely (constitutively) expressed in all cell types since certain proteins (and RNAs) are involved in the basic metabolic processes common to all cell types. Other genes are expressed in one cell type but not another (e.g., certain immune cells normally synthesize antibodies, but neurons do not). Thus, different cell types arise because of differential gene expression, and the RNA and protein content of different cell types shows considerable variation.', 'af521ffa-f57b-46d6-a124-40bf570ffc65': 'Changes to DNA content and rearrangement are addressed elsewhere. Briefly, DNA of different cell types does not vary in either amount or type. However, highly specialized cases are known to exist where DNA loss, rearrangement, and amplification profoundly influence gene expression in isolated situations.'}"
Figure 13.9,cell_bio/images/Figure 13.9.jpg,Figure 13.9: Male karyotype with G-banding patterns.,"The pattern of light and dark bands on each chromosome is numbered on each arm from the centromere to the telomere, and comparison of a patient sample to a standard map can be used to precisely identify changes in chromosome structure. Microdeletion syndromes can be detected with this technique (figure 13.9).","{'d9a33d67-8fa0-42b6-ab41-381586aa92fc': 'Karyotyping can be used to look at general chromosome morphology and chromosome number. To do this, cells are harvested and arrested in metaphase allowing for the chromosomes to be fixed, spread on slides, and stained by one of several techniques. Giemsa banding (G banding) is the gold standard for the detection and characterization of structural and numerical genomic abnormalities in clinical diagnostic settings for both constitutional (postnatal or prenatal) and acquired (cancer) disorders.', 'dbc2a865-a717-4143-ab7b-aa16a85baf23': 'The pattern of light and dark bands on each chromosome is numbered on each arm from the centromere to the telomere, and comparison of a patient sample to a standard map can be used to precisely identify changes in chromosome structure. Microdeletion syndromes can be detected with this technique (figure 13.9).', '39d4cfc6-ce04-47b5-98c5-d4c1ab14badd': 'Different types of electrophoresis can be used to look at various changes at the level of the DNA (genome), RNA (transcriptome), or protein (proteome). In all cases, a sample (DNA, RNA, protein) is run on a gel (electrophoresis) and is then examined using a probe specific to the sample.', '4acfe7ef-a0ad-4d50-b52c-c791e0319240': 'Southern blots are designed to examine changes in DNA. DNA, typically genomic DNA, is probed with a DNA probe complementary to the region of interest in the genome (figure 13.12).', '571d2bed-0971-44cb-a251-73c8cd57b305': 'Northern blots are designed to examine changes in RNA. RNA is probed with a DNA probe complementary to the transcript of interest. This will detect changes in gene expression.', '031a0f8f-c5e9-4c3c-9765-046de41e93f2': 'Western blots are designed to examine changes in protein size and amount. Cell lysates or protein isolates are probed with an antibody specific to the protein of interest. This will detect changes in protein expression.', 'd549bc4e-7163-4272-9347-ceb25f5ae2e0': '13.2 References and resources', '19b8358b-71ca-4e78-8147-e5e8b16a93f5': 'Lieberman M, Peet A. Figure 13.11 Overview of polymerase chain reaction. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 329. Figure 17.10 Polymerase chain reaction (PCR). 2017.', '455d3428-bedc-45f5-9469-ad3db59bacba': 'National Cancer Institute. Figure 13.9 Male karyotype with G-banding patterns. Karyotype (normal). Public domain. From Wikimedia Commons.', '33f8d57d-33e6-4e6d-8074-027b7d7b4364': 'Some genes (the so-called “house-keeping genes”) are likely (constitutively) expressed in all cell types since certain proteins (and RNAs) are involved in the basic metabolic processes common to all cell types. Other genes are expressed in one cell type but not another (e.g., certain immune cells normally synthesize antibodies, but neurons do not). Thus, different cell types arise because of differential gene expression, and the RNA and protein content of different cell types shows considerable variation.', 'af521ffa-f57b-46d6-a124-40bf570ffc65': 'Changes to DNA content and rearrangement are addressed elsewhere. Briefly, DNA of different cell types does not vary in either amount or type. However, highly specialized cases are known to exist where DNA loss, rearrangement, and amplification profoundly influence gene expression in isolated situations.'}"
Figure 13.10,cell_bio/images/Figure 13.10.jpg,Figure 13.10: Schematic of Sanger sequencing technique.,"The DNA sample to be sequenced is denatured (separated into two strands by heating it to high temperatures). The DNA is divided into four tubes in which a primer, DNA polymerase, and all four nucleoside triphosphates (A, T, G, and C) are added. In addition, limited quantities of one of the four dideoxynucleoside triphosphates (ddCTP, ddATP, ddGTP, and ddTTP) are added to each tube respectively. The tubes are labeled as A, T, G, and C according to the ddNTP added. For detection purposes, each of the four dideoxynucleotides carries a different fluorescent label. Chain elongation continues until a fluorescent dideoxy nucleotide is incorporated, after which no further elongation takes place. After the reaction is over, electrophoresis is performed. Even a difference in length of a single base can be detected (figure 13.10).","{'5653a75e-f441-448c-8479-8e3e4d1ed470': 'Sanger sequencing is commonly referred to as the dideoxy chain termination method. The method is based on the use of chain terminators, the dideoxynucleotides (ddNTPs). The ddNTPSs differ from the deoxynucleotides by the lack of a free 3′ OH group on the five-carbon sugar. If a ddNTP is added to a growing DNA strand, the chain cannot be extended any further because the free 3′ OH group needed to add another nucleotide is not available. By using a predetermined ratio of deoxyribonucleotides to dideoxynucleotides, it is possible to generate DNA fragments of different sizes.', '0501f9ea-2fef-439e-be9a-780f14a30814': 'The DNA sample to be sequenced is denatured (separated into two strands by heating it to high temperatures). The DNA is divided into four tubes in which a primer, DNA polymerase, and all four nucleoside triphosphates (A, T, G, and C) are added. In addition, limited quantities of one of the four dideoxynucleoside triphosphates (ddCTP, ddATP, ddGTP, and ddTTP) are added to each tube respectively. The tubes are labeled as A, T, G, and C according to the ddNTP added. For detection purposes, each of the four dideoxynucleotides carries a different fluorescent label. Chain elongation continues until a fluorescent dideoxy nucleotide is incorporated, after which no further elongation takes place. After the reaction is over, electrophoresis is performed. Even a difference in length of a single base can be detected (figure 13.10).', '39d4cfc6-ce04-47b5-98c5-d4c1ab14badd': 'Different types of electrophoresis can be used to look at various changes at the level of the DNA (genome), RNA (transcriptome), or protein (proteome). In all cases, a sample (DNA, RNA, protein) is run on a gel (electrophoresis) and is then examined using a probe specific to the sample.', '4acfe7ef-a0ad-4d50-b52c-c791e0319240': 'Southern blots are designed to examine changes in DNA. DNA, typically genomic DNA, is probed with a DNA probe complementary to the region of interest in the genome (figure 13.12).', '571d2bed-0971-44cb-a251-73c8cd57b305': 'Northern blots are designed to examine changes in RNA. RNA is probed with a DNA probe complementary to the transcript of interest. This will detect changes in gene expression.', '031a0f8f-c5e9-4c3c-9765-046de41e93f2': 'Western blots are designed to examine changes in protein size and amount. Cell lysates or protein isolates are probed with an antibody specific to the protein of interest. This will detect changes in protein expression.', 'd549bc4e-7163-4272-9347-ceb25f5ae2e0': '13.2 References and resources', '19b8358b-71ca-4e78-8147-e5e8b16a93f5': 'Lieberman M, Peet A. Figure 13.11 Overview of polymerase chain reaction. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 329. Figure 17.10 Polymerase chain reaction (PCR). 2017.', '455d3428-bedc-45f5-9469-ad3db59bacba': 'National Cancer Institute. Figure 13.9 Male karyotype with G-banding patterns. Karyotype (normal). Public domain. From Wikimedia Commons.', '33f8d57d-33e6-4e6d-8074-027b7d7b4364': 'Some genes (the so-called “house-keeping genes”) are likely (constitutively) expressed in all cell types since certain proteins (and RNAs) are involved in the basic metabolic processes common to all cell types. Other genes are expressed in one cell type but not another (e.g., certain immune cells normally synthesize antibodies, but neurons do not). Thus, different cell types arise because of differential gene expression, and the RNA and protein content of different cell types shows considerable variation.', 'af521ffa-f57b-46d6-a124-40bf570ffc65': 'Changes to DNA content and rearrangement are addressed elsewhere. Briefly, DNA of different cell types does not vary in either amount or type. However, highly specialized cases are known to exist where DNA loss, rearrangement, and amplification profoundly influence gene expression in isolated situations.'}"
Figure 13.11,cell_bio/images/Figure 13.11.jpg,Figure 13.11: Overview of polymerase chain reaction.,"DNA analysis often requires focusing on one or more specific genome regions. Polymerase chain reaction (PCR) is a technique that scientists use to amplify specific DNA regions for further analysis (figure 13.11). Researchers use PCR for many purposes in laboratories, such as cloning gene fragments to analyze genetic diseases, identifying contaminant foreign DNA in a sample, and amplifying DNA for sequencing. More practical applications include determining paternity and detecting genetic diseases.","{'a4ad8cba-34e8-4244-b2ab-2b20b1831f99': 'DNA analysis often requires focusing on one or more specific genome regions. Polymerase chain reaction (PCR) is a technique that scientists use to amplify specific DNA regions for further analysis (figure 13.11). Researchers use PCR for many purposes in laboratories, such as cloning gene fragments to analyze genetic diseases, identifying contaminant foreign DNA in a sample, and amplifying DNA for sequencing. More practical applications include determining paternity and detecting genetic diseases.', 'e21cf8c4-a95c-42d2-ab65-3b931943cd3f': 'Scientists use polymerase chain reaction, or PCR, to amplify a specific DNA sequence. Primers are short pieces of DNA complementary to each end of the target sequence combined with genomic DNA, Taq polymerase, and deoxynucleotides.', '20dae2ab-dea0-4bf5-9340-aa075cdbd381': 'Reverse transcriptase PCR (RT-PCR) is similar to PCR, but cDNA is made from an RNA template before PCR begins. DNA fragments can also be amplified from an RNA template in a process called reverse transcriptase PCR (RT-PCR). The first step is to recreate the original DNA template strand (called cDNA) by applying DNA nucleotides to the mRNA. This process is called reverse transcription. This requires the presence of an enzyme called reverse transcriptase. After the cDNA is made, regular PCR can be used to amplify it.', '39d4cfc6-ce04-47b5-98c5-d4c1ab14badd': 'Different types of electrophoresis can be used to look at various changes at the level of the DNA (genome), RNA (transcriptome), or protein (proteome). In all cases, a sample (DNA, RNA, protein) is run on a gel (electrophoresis) and is then examined using a probe specific to the sample.', '4acfe7ef-a0ad-4d50-b52c-c791e0319240': 'Southern blots are designed to examine changes in DNA. DNA, typically genomic DNA, is probed with a DNA probe complementary to the region of interest in the genome (figure 13.12).', '571d2bed-0971-44cb-a251-73c8cd57b305': 'Northern blots are designed to examine changes in RNA. RNA is probed with a DNA probe complementary to the transcript of interest. This will detect changes in gene expression.', '031a0f8f-c5e9-4c3c-9765-046de41e93f2': 'Western blots are designed to examine changes in protein size and amount. Cell lysates or protein isolates are probed with an antibody specific to the protein of interest. This will detect changes in protein expression.', 'd549bc4e-7163-4272-9347-ceb25f5ae2e0': '13.2 References and resources', '19b8358b-71ca-4e78-8147-e5e8b16a93f5': 'Lieberman M, Peet A. Figure 13.11 Overview of polymerase chain reaction. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 329. Figure 17.10 Polymerase chain reaction (PCR). 2017.', '455d3428-bedc-45f5-9469-ad3db59bacba': 'National Cancer Institute. Figure 13.9 Male karyotype with G-banding patterns. Karyotype (normal). Public domain. From Wikimedia Commons.', '33f8d57d-33e6-4e6d-8074-027b7d7b4364': 'Some genes (the so-called “house-keeping genes”) are likely (constitutively) expressed in all cell types since certain proteins (and RNAs) are involved in the basic metabolic processes common to all cell types. Other genes are expressed in one cell type but not another (e.g., certain immune cells normally synthesize antibodies, but neurons do not). Thus, different cell types arise because of differential gene expression, and the RNA and protein content of different cell types shows considerable variation.', 'af521ffa-f57b-46d6-a124-40bf570ffc65': 'Changes to DNA content and rearrangement are addressed elsewhere. Briefly, DNA of different cell types does not vary in either amount or type. However, highly specialized cases are known to exist where DNA loss, rearrangement, and amplification profoundly influence gene expression in isolated situations.'}"
Figure 13.12,cell_bio/images/Figure 13.12.jpg,Figure 13.12: Schematic of southern blotting technique.,"Southern blots are designed to examine changes in DNA. DNA, typically genomic DNA, is probed with a DNA probe complementary to the region of interest in the genome (figure 13.12).","{'39d4cfc6-ce04-47b5-98c5-d4c1ab14badd': 'Different types of electrophoresis can be used to look at various changes at the level of the DNA (genome), RNA (transcriptome), or protein (proteome). In all cases, a sample (DNA, RNA, protein) is run on a gel (electrophoresis) and is then examined using a probe specific to the sample.', '4acfe7ef-a0ad-4d50-b52c-c791e0319240': 'Southern blots are designed to examine changes in DNA. DNA, typically genomic DNA, is probed with a DNA probe complementary to the region of interest in the genome (figure 13.12).', '571d2bed-0971-44cb-a251-73c8cd57b305': 'Northern blots are designed to examine changes in RNA. RNA is probed with a DNA probe complementary to the transcript of interest. This will detect changes in gene expression.', '031a0f8f-c5e9-4c3c-9765-046de41e93f2': 'Western blots are designed to examine changes in protein size and amount. Cell lysates or protein isolates are probed with an antibody specific to the protein of interest. This will detect changes in protein expression.', 'd549bc4e-7163-4272-9347-ceb25f5ae2e0': '13.2 References and resources', '19b8358b-71ca-4e78-8147-e5e8b16a93f5': 'Lieberman M, Peet A. Figure 13.11 Overview of polymerase chain reaction. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 329. Figure 17.10 Polymerase chain reaction (PCR). 2017.', '455d3428-bedc-45f5-9469-ad3db59bacba': 'National Cancer Institute. Figure 13.9 Male karyotype with G-banding patterns. Karyotype (normal). Public domain. From Wikimedia Commons.', '33f8d57d-33e6-4e6d-8074-027b7d7b4364': 'Some genes (the so-called “house-keeping genes”) are likely (constitutively) expressed in all cell types since certain proteins (and RNAs) are involved in the basic metabolic processes common to all cell types. Other genes are expressed in one cell type but not another (e.g., certain immune cells normally synthesize antibodies, but neurons do not). Thus, different cell types arise because of differential gene expression, and the RNA and protein content of different cell types shows considerable variation.', 'af521ffa-f57b-46d6-a124-40bf570ffc65': 'Changes to DNA content and rearrangement are addressed elsewhere. Briefly, DNA of different cell types does not vary in either amount or type. However, highly specialized cases are known to exist where DNA loss, rearrangement, and amplification profoundly influence gene expression in isolated situations.'}"
Figure 13.8,cell_bio/images/Figure 13.8.jpg,Figure 13.8: Basic process for DNA extraction.,"To study or manipulate nucleic acids, one must first isolate or extract the DNA or RNA from the cells. Most nucleic acid extraction techniques involve steps to break open the cell and use enzymatic reactions to destroy all macromolecules that are not desired. Enzymes such as proteases that break down proteins inactivate macromolecules, and ribonucleases (RNAses) that break down RNA are inhibited to ensure sample stability. Using alcohol precipitates the DNA. Human genomic DNA is usually visible as a gelatinous, white mass. One can store the DNA samples frozen at ‒80°C for several years (figure 13.8).","{'dfe65351-1ba7-4fa8-960e-e44770fe1482': 'To study or manipulate nucleic acids, one must first isolate or extract the DNA or RNA from the cells. Most nucleic acid extraction techniques involve steps to break open the cell and use enzymatic reactions to destroy all macromolecules that are not desired. Enzymes such as proteases that break down proteins inactivate macromolecules, and ribonucleases (RNAses) that break down RNA are inhibited to ensure sample stability. Using alcohol precipitates the DNA. Human genomic DNA is usually visible as a gelatinous, white mass. One can store the DNA samples frozen at ‒80°C for several years (figure 13.8).', '39d4cfc6-ce04-47b5-98c5-d4c1ab14badd': 'Different types of electrophoresis can be used to look at various changes at the level of the DNA (genome), RNA (transcriptome), or protein (proteome). In all cases, a sample (DNA, RNA, protein) is run on a gel (electrophoresis) and is then examined using a probe specific to the sample.', '4acfe7ef-a0ad-4d50-b52c-c791e0319240': 'Southern blots are designed to examine changes in DNA. DNA, typically genomic DNA, is probed with a DNA probe complementary to the region of interest in the genome (figure 13.12).', '571d2bed-0971-44cb-a251-73c8cd57b305': 'Northern blots are designed to examine changes in RNA. RNA is probed with a DNA probe complementary to the transcript of interest. This will detect changes in gene expression.', '031a0f8f-c5e9-4c3c-9765-046de41e93f2': 'Western blots are designed to examine changes in protein size and amount. Cell lysates or protein isolates are probed with an antibody specific to the protein of interest. This will detect changes in protein expression.', 'd549bc4e-7163-4272-9347-ceb25f5ae2e0': '13.2 References and resources', '19b8358b-71ca-4e78-8147-e5e8b16a93f5': 'Lieberman M, Peet A. Figure 13.11 Overview of polymerase chain reaction. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 329. Figure 17.10 Polymerase chain reaction (PCR). 2017.', '455d3428-bedc-45f5-9469-ad3db59bacba': 'National Cancer Institute. Figure 13.9 Male karyotype with G-banding patterns. Karyotype (normal). Public domain. From Wikimedia Commons.', '33f8d57d-33e6-4e6d-8074-027b7d7b4364': 'Some genes (the so-called “house-keeping genes”) are likely (constitutively) expressed in all cell types since certain proteins (and RNAs) are involved in the basic metabolic processes common to all cell types. Other genes are expressed in one cell type but not another (e.g., certain immune cells normally synthesize antibodies, but neurons do not). Thus, different cell types arise because of differential gene expression, and the RNA and protein content of different cell types shows considerable variation.', 'af521ffa-f57b-46d6-a124-40bf570ffc65': 'Changes to DNA content and rearrangement are addressed elsewhere. Briefly, DNA of different cell types does not vary in either amount or type. However, highly specialized cases are known to exist where DNA loss, rearrangement, and amplification profoundly influence gene expression in isolated situations.'}"
Figure 13.10,cell_bio/images/Figure 13.10.jpg,Figure 13.10: Schematic of Sanger sequencing technique.,"The DNA sample to be sequenced is denatured (separated into two strands by heating it to high temperatures). The DNA is divided into four tubes in which a primer, DNA polymerase, and all four nucleoside triphosphates (A, T, G, and C) are added. In addition, limited quantities of one of the four dideoxynucleoside triphosphates (ddCTP, ddATP, ddGTP, and ddTTP) are added to each tube respectively. The tubes are labeled as A, T, G, and C according to the ddNTP added. For detection purposes, each of the four dideoxynucleotides carries a different fluorescent label. Chain elongation continues until a fluorescent dideoxy nucleotide is incorporated, after which no further elongation takes place. After the reaction is over, electrophoresis is performed. Even a difference in length of a single base can be detected (figure 13.10).","{'5653a75e-f441-448c-8479-8e3e4d1ed470': 'Sanger sequencing is commonly referred to as the dideoxy chain termination method. The method is based on the use of chain terminators, the dideoxynucleotides (ddNTPs). The ddNTPSs differ from the deoxynucleotides by the lack of a free 3′ OH group on the five-carbon sugar. If a ddNTP is added to a growing DNA strand, the chain cannot be extended any further because the free 3′ OH group needed to add another nucleotide is not available. By using a predetermined ratio of deoxyribonucleotides to dideoxynucleotides, it is possible to generate DNA fragments of different sizes.', '0501f9ea-2fef-439e-be9a-780f14a30814': 'The DNA sample to be sequenced is denatured (separated into two strands by heating it to high temperatures). The DNA is divided into four tubes in which a primer, DNA polymerase, and all four nucleoside triphosphates (A, T, G, and C) are added. In addition, limited quantities of one of the four dideoxynucleoside triphosphates (ddCTP, ddATP, ddGTP, and ddTTP) are added to each tube respectively. The tubes are labeled as A, T, G, and C according to the ddNTP added. For detection purposes, each of the four dideoxynucleotides carries a different fluorescent label. Chain elongation continues until a fluorescent dideoxy nucleotide is incorporated, after which no further elongation takes place. After the reaction is over, electrophoresis is performed. Even a difference in length of a single base can be detected (figure 13.10).', '39d4cfc6-ce04-47b5-98c5-d4c1ab14badd': 'Different types of electrophoresis can be used to look at various changes at the level of the DNA (genome), RNA (transcriptome), or protein (proteome). In all cases, a sample (DNA, RNA, protein) is run on a gel (electrophoresis) and is then examined using a probe specific to the sample.', '4acfe7ef-a0ad-4d50-b52c-c791e0319240': 'Southern blots are designed to examine changes in DNA. DNA, typically genomic DNA, is probed with a DNA probe complementary to the region of interest in the genome (figure 13.12).', '571d2bed-0971-44cb-a251-73c8cd57b305': 'Northern blots are designed to examine changes in RNA. RNA is probed with a DNA probe complementary to the transcript of interest. This will detect changes in gene expression.', '031a0f8f-c5e9-4c3c-9765-046de41e93f2': 'Western blots are designed to examine changes in protein size and amount. Cell lysates or protein isolates are probed with an antibody specific to the protein of interest. This will detect changes in protein expression.', 'd549bc4e-7163-4272-9347-ceb25f5ae2e0': '13.2 References and resources', '19b8358b-71ca-4e78-8147-e5e8b16a93f5': 'Lieberman M, Peet A. Figure 13.11 Overview of polymerase chain reaction. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 329. Figure 17.10 Polymerase chain reaction (PCR). 2017.', '455d3428-bedc-45f5-9469-ad3db59bacba': 'National Cancer Institute. Figure 13.9 Male karyotype with G-banding patterns. Karyotype (normal). Public domain. From Wikimedia Commons.', '33f8d57d-33e6-4e6d-8074-027b7d7b4364': 'Some genes (the so-called “house-keeping genes”) are likely (constitutively) expressed in all cell types since certain proteins (and RNAs) are involved in the basic metabolic processes common to all cell types. Other genes are expressed in one cell type but not another (e.g., certain immune cells normally synthesize antibodies, but neurons do not). Thus, different cell types arise because of differential gene expression, and the RNA and protein content of different cell types shows considerable variation.', 'af521ffa-f57b-46d6-a124-40bf570ffc65': 'Changes to DNA content and rearrangement are addressed elsewhere. Briefly, DNA of different cell types does not vary in either amount or type. However, highly specialized cases are known to exist where DNA loss, rearrangement, and amplification profoundly influence gene expression in isolated situations.'}"
Figure 13.11,cell_bio/images/Figure 13.11.jpg,Figure 13.11: Overview of polymerase chain reaction.,"DNA analysis often requires focusing on one or more specific genome regions. Polymerase chain reaction (PCR) is a technique that scientists use to amplify specific DNA regions for further analysis (figure 13.11). Researchers use PCR for many purposes in laboratories, such as cloning gene fragments to analyze genetic diseases, identifying contaminant foreign DNA in a sample, and amplifying DNA for sequencing. More practical applications include determining paternity and detecting genetic diseases.","{'a4ad8cba-34e8-4244-b2ab-2b20b1831f99': 'DNA analysis often requires focusing on one or more specific genome regions. Polymerase chain reaction (PCR) is a technique that scientists use to amplify specific DNA regions for further analysis (figure 13.11). Researchers use PCR for many purposes in laboratories, such as cloning gene fragments to analyze genetic diseases, identifying contaminant foreign DNA in a sample, and amplifying DNA for sequencing. More practical applications include determining paternity and detecting genetic diseases.', 'e21cf8c4-a95c-42d2-ab65-3b931943cd3f': 'Scientists use polymerase chain reaction, or PCR, to amplify a specific DNA sequence. Primers are short pieces of DNA complementary to each end of the target sequence combined with genomic DNA, Taq polymerase, and deoxynucleotides.', '20dae2ab-dea0-4bf5-9340-aa075cdbd381': 'Reverse transcriptase PCR (RT-PCR) is similar to PCR, but cDNA is made from an RNA template before PCR begins. DNA fragments can also be amplified from an RNA template in a process called reverse transcriptase PCR (RT-PCR). The first step is to recreate the original DNA template strand (called cDNA) by applying DNA nucleotides to the mRNA. This process is called reverse transcription. This requires the presence of an enzyme called reverse transcriptase. After the cDNA is made, regular PCR can be used to amplify it.', '39d4cfc6-ce04-47b5-98c5-d4c1ab14badd': 'Different types of electrophoresis can be used to look at various changes at the level of the DNA (genome), RNA (transcriptome), or protein (proteome). In all cases, a sample (DNA, RNA, protein) is run on a gel (electrophoresis) and is then examined using a probe specific to the sample.', '4acfe7ef-a0ad-4d50-b52c-c791e0319240': 'Southern blots are designed to examine changes in DNA. DNA, typically genomic DNA, is probed with a DNA probe complementary to the region of interest in the genome (figure 13.12).', '571d2bed-0971-44cb-a251-73c8cd57b305': 'Northern blots are designed to examine changes in RNA. RNA is probed with a DNA probe complementary to the transcript of interest. This will detect changes in gene expression.', '031a0f8f-c5e9-4c3c-9765-046de41e93f2': 'Western blots are designed to examine changes in protein size and amount. Cell lysates or protein isolates are probed with an antibody specific to the protein of interest. This will detect changes in protein expression.', 'd549bc4e-7163-4272-9347-ceb25f5ae2e0': '13.2 References and resources', '19b8358b-71ca-4e78-8147-e5e8b16a93f5': 'Lieberman M, Peet A. Figure 13.11 Overview of polymerase chain reaction. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 329. Figure 17.10 Polymerase chain reaction (PCR). 2017.', '455d3428-bedc-45f5-9469-ad3db59bacba': 'National Cancer Institute. Figure 13.9 Male karyotype with G-banding patterns. Karyotype (normal). Public domain. From Wikimedia Commons.', '33f8d57d-33e6-4e6d-8074-027b7d7b4364': 'Some genes (the so-called “house-keeping genes”) are likely (constitutively) expressed in all cell types since certain proteins (and RNAs) are involved in the basic metabolic processes common to all cell types. Other genes are expressed in one cell type but not another (e.g., certain immune cells normally synthesize antibodies, but neurons do not). Thus, different cell types arise because of differential gene expression, and the RNA and protein content of different cell types shows considerable variation.', 'af521ffa-f57b-46d6-a124-40bf570ffc65': 'Changes to DNA content and rearrangement are addressed elsewhere. Briefly, DNA of different cell types does not vary in either amount or type. However, highly specialized cases are known to exist where DNA loss, rearrangement, and amplification profoundly influence gene expression in isolated situations.'}"
Figure 13.9,cell_bio/images/Figure 13.9.jpg,Figure 13.9: Male karyotype with G-banding patterns.,"The pattern of light and dark bands on each chromosome is numbered on each arm from the centromere to the telomere, and comparison of a patient sample to a standard map can be used to precisely identify changes in chromosome structure. Microdeletion syndromes can be detected with this technique (figure 13.9).","{'d9a33d67-8fa0-42b6-ab41-381586aa92fc': 'Karyotyping can be used to look at general chromosome morphology and chromosome number. To do this, cells are harvested and arrested in metaphase allowing for the chromosomes to be fixed, spread on slides, and stained by one of several techniques. Giemsa banding (G banding) is the gold standard for the detection and characterization of structural and numerical genomic abnormalities in clinical diagnostic settings for both constitutional (postnatal or prenatal) and acquired (cancer) disorders.', 'dbc2a865-a717-4143-ab7b-aa16a85baf23': 'The pattern of light and dark bands on each chromosome is numbered on each arm from the centromere to the telomere, and comparison of a patient sample to a standard map can be used to precisely identify changes in chromosome structure. Microdeletion syndromes can be detected with this technique (figure 13.9).', '39d4cfc6-ce04-47b5-98c5-d4c1ab14badd': 'Different types of electrophoresis can be used to look at various changes at the level of the DNA (genome), RNA (transcriptome), or protein (proteome). In all cases, a sample (DNA, RNA, protein) is run on a gel (electrophoresis) and is then examined using a probe specific to the sample.', '4acfe7ef-a0ad-4d50-b52c-c791e0319240': 'Southern blots are designed to examine changes in DNA. DNA, typically genomic DNA, is probed with a DNA probe complementary to the region of interest in the genome (figure 13.12).', '571d2bed-0971-44cb-a251-73c8cd57b305': 'Northern blots are designed to examine changes in RNA. RNA is probed with a DNA probe complementary to the transcript of interest. This will detect changes in gene expression.', '031a0f8f-c5e9-4c3c-9765-046de41e93f2': 'Western blots are designed to examine changes in protein size and amount. Cell lysates or protein isolates are probed with an antibody specific to the protein of interest. This will detect changes in protein expression.', 'd549bc4e-7163-4272-9347-ceb25f5ae2e0': '13.2 References and resources', '19b8358b-71ca-4e78-8147-e5e8b16a93f5': 'Lieberman M, Peet A. Figure 13.11 Overview of polymerase chain reaction. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 329. Figure 17.10 Polymerase chain reaction (PCR). 2017.', '455d3428-bedc-45f5-9469-ad3db59bacba': 'National Cancer Institute. Figure 13.9 Male karyotype with G-banding patterns. Karyotype (normal). Public domain. From Wikimedia Commons.', '33f8d57d-33e6-4e6d-8074-027b7d7b4364': 'Some genes (the so-called “house-keeping genes”) are likely (constitutively) expressed in all cell types since certain proteins (and RNAs) are involved in the basic metabolic processes common to all cell types. Other genes are expressed in one cell type but not another (e.g., certain immune cells normally synthesize antibodies, but neurons do not). Thus, different cell types arise because of differential gene expression, and the RNA and protein content of different cell types shows considerable variation.', 'af521ffa-f57b-46d6-a124-40bf570ffc65': 'Changes to DNA content and rearrangement are addressed elsewhere. Briefly, DNA of different cell types does not vary in either amount or type. However, highly specialized cases are known to exist where DNA loss, rearrangement, and amplification profoundly influence gene expression in isolated situations.'}"
Figure 12.1,cell_bio/images/Figure 12.1.jpg,Figure 12.1: Example of transcriptional complex involving two separate genes.,"Enhancer regions are binding sequences, or sites, for specific transcription factors. When a protein transcription factor binds to its enhancer sequence, the shape of the protein changes, allowing it to interact with proteins at the promotor site. However, since the enhancer region may be distant from the promoter, the DNA must bend to allow the proteins at the two sites to come into contact. DNA-bending proteins help bend the DNA and bring the enhancer and promoter regions together (figure 12.1). This shape change allows for the interaction of the specific activator proteins bound to the enhancers with the general transcription factors bound to the promoter region and the RNA polymerase. Two different genes may have the same promoter but different distal control elements, enabling differential gene expression.","{'367061fe-4d87-4a4d-b72b-297167a2fefc': 'Along with general transcription factors, there are additional regions that help increase or enhance transcription. These regions, called enhancers, are not necessarily close to the genes they enhance. They can be located upstream of a gene, within the coding region of the gene, downstream of a gene, or\xa0thousands of nucleotides away.', 'd5b65959-dc71-4f4e-8bb0-4a151b1b235a': 'Enhancer regions are binding sequences, or sites, for specific transcription factors. When a protein transcription factor binds to its enhancer sequence, the shape of the protein changes, allowing it to interact with proteins at the promotor site. However, since the enhancer region may be distant from the promoter, the DNA must bend to allow the proteins at the two sites to come into contact. DNA-bending proteins help bend the DNA and bring the enhancer and promoter regions together (figure 12.1). This shape change allows for the interaction of the specific activator proteins bound to the enhancers with the general transcription factors bound to the promoter region and the RNA polymerase. Two different genes may have the same promoter but different distal control elements, enabling differential gene expression.', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.2,cell_bio/images/Figure 12.2.jpg,Figure 12.2: Modification of DNA and histones can alter DNA accessibility and therefore transcription.,"Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptional repressors can bind to promoter or enhancer regions and block transcription. Like the transcriptional activators, repressors respond to external stimuli preventing the binding of activating transcription factors. This is often done by histone deacetylation, which increases the interaction of DNA and histones (figure 12.2).","{'6a3c0cfe-dbda-4ee9-8e2d-0b2c326af860': 'Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptional repressors can bind to promoter or enhancer regions and block transcription. Like the transcriptional activators, repressors respond to external stimuli preventing the binding of activating transcription factors. This is often done by histone deacetylation, which increases the interaction of DNA and histones (figure 12.2).', 'a022a82e-54e6-499b-ba54-bfdd54a06938': 'Structurally, transcription factors share similar characteristics but can take on very different secondary structures. Common examples of transcription factors include: Zn fingers, helix-loop-helixs, and leucine zippers. Regardless of structure, common characteristics include:', '6dca7235-56cb-43f1-9546-f97a92560741': 'As noted above, one of the major roles of transcription factors is to bend or remodel the DNA in a way to allow for interactions of transcription factors and their binding sites. Chromatin remodeling by modifications of the histones (through acetylation or shifting) is common (figure 12.2).', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.2,cell_bio/images/Figure 12.2.jpg,Figure 12.2: Modification of DNA and histones can alter DNA accessibility and therefore transcription.,"Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptional repressors can bind to promoter or enhancer regions and block transcription. Like the transcriptional activators, repressors respond to external stimuli preventing the binding of activating transcription factors. This is often done by histone deacetylation, which increases the interaction of DNA and histones (figure 12.2).","{'6a3c0cfe-dbda-4ee9-8e2d-0b2c326af860': 'Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptional repressors can bind to promoter or enhancer regions and block transcription. Like the transcriptional activators, repressors respond to external stimuli preventing the binding of activating transcription factors. This is often done by histone deacetylation, which increases the interaction of DNA and histones (figure 12.2).', 'a022a82e-54e6-499b-ba54-bfdd54a06938': 'Structurally, transcription factors share similar characteristics but can take on very different secondary structures. Common examples of transcription factors include: Zn fingers, helix-loop-helixs, and leucine zippers. Regardless of structure, common characteristics include:', '6dca7235-56cb-43f1-9546-f97a92560741': 'As noted above, one of the major roles of transcription factors is to bend or remodel the DNA in a way to allow for interactions of transcription factors and their binding sites. Chromatin remodeling by modifications of the histones (through acetylation or shifting) is common (figure 12.2).', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.3,cell_bio/images/Figure 12.3.jpg,Figure 12.3: Five common modes of alternative splicing.,"Alternative RNA splicing is a mechanism that allows different protein products to be produced from one gene when different combinations of exons are combined to form the mRNA. This alternative splicing can be haphazard, but more often it is controlled and acts as a mechanism of gene regulation, with the frequency of different splicing alternatives controlled by the cell as a way to control the production of different protein products in different cells or at different stages of development. Alternative splicing is a common mechanism of gene regulation in eukaryotes; according to one estimate, 70 percent of genes in humans are expressed as multiple proteins through alternative splicing. Although there are multiple ways to alternatively splice RNA transcripts, the original 5′-3′ order of the exons is always conserved. That is, a transcript with exons 1 2 3 4 5 6 7 might be spliced 1 2 4 5 6 7 or 1 2 3 6 7, but never 1 2 5 4 3 6 7 (figure 12.3).","{'d6169e44-138e-4b82-a4fd-9cec550e51c5': 'Alternative RNA splicing is a mechanism that allows different protein products to be produced from one gene when different combinations of exons are combined to form the mRNA. This alternative splicing can be haphazard, but more often it is controlled and acts as a mechanism of gene regulation, with the frequency of different splicing alternatives controlled by the cell as a way to control the production of different protein products in different cells or at different stages of development. Alternative splicing is a common mechanism of gene regulation in eukaryotes; according to one estimate, 70 percent of genes in humans are expressed as multiple proteins through alternative splicing. Although there are multiple ways to alternatively splice RNA transcripts, the original 5′-3′ order of the exons is always conserved. That is, a transcript with exons 1 2 3 4 5 6 7 might be spliced 1 2 4 5 6 7 or 1 2 3 6 7, but never 1 2 5 4 3 6 7 (figure 12.3).', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.4,cell_bio/images/Figure 12.4.jpg,Figure 12.4: Regulation of translational initiation.,"The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly, and translation is impeded (figure 12.4).","{'37bdb907-a86b-4f97-ab65-584c9710c87a': 'In translation, the complex that assembles to start the process is referred to as the translation initiation complex, and similar to transcription, this complex can be activated or inhibited. In eukaryotes, translation is initiated by binding the initiating met-tRNAi to the 40S ribosome.', '926b42ec-c92b-44c7-97f6-44e2479f1895': 'Initially the met-tRNAi is brought to the 40S ribosome by a protein initiation factor, eukaryotic initiation factor-2 (eIF-2). The eIF-2 protein binds to the high-energy molecule guanosine triphosphate (GTP), and the tRNA-eIF2-GTP complex then binds to the 40S ribosome.', '770b9711-0232-40e8-ab64-40ee0d174bd2': 'The cap-binding protein eIF4F brings the mRNA complex together with the 40S ribosome complex. The ribosome then scans along the mRNA until it finds a start codon AUG. When the anticodon of the initiator tRNA and the start codon are aligned, the GTP is hydrolyzed, the initiation factors are released, and the large 60S ribosomal subunit binds to form the translation complex. Insulin increases the efficiency of formation of the cap-binding complex, therefore increasing the rate of protein synthesis.', '6688d9da-2c39-4d8d-be5d-63939d208064': 'The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly, and translation is impeded (figure 12.4).', '457442d7-5171-457c-9e5c-05c7bf133402': 'When eIF-2 remains unphosphorylated, the initiation complex can form normally, and translation can continue.', '2e4603d9-00fc-4d15-bf97-3255dbe2b61c': 'Translation is initiated by the assembly of the small ribosomal subunit (40S) with initiation factors (IF), which recognize the 5ʼ cap of the mRNA. This is referred to as the cap-binding complex, and this will scan the mRNA for the initial AUG needed to start translation. Once at the cap, the initiation complex tracks along the mRNA in the 5′ to 3′ direction, searching for the AUG start codon. Many eukaryotic mRNAs are translated from the first AUG, but this is not always the case. Once the appropriate AUG is identified, the other proteins and CBP dissociate, and the 60S subunit binds to the complex of Met-tRNAi, mRNA, and the 40S subunit. This step completes the initiation of translation in eukaryotes (figure 11.8).', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.5,cell_bio/images/Figure 12.5.jpg,Figure 12.5: RNA-Binding proteins can increase stability of the transcript.,"Binding of proteins to the RNA can also influence its stability. Proteins called RNA-binding proteins, or RBPs, can bind to the regions of the mRNA just upstream or downstream of the protein-coding region. These regions in the RNA that are not translated into protein are called the untranslated regions, or UTRs (figure 12.5). They are not introns (those have been removed in the nucleus). Rather, these are regions that regulate mRNA localization, stability, and protein translation. The region just before the protein-coding region is called the 5′ UTR, whereas the region after the coding region is called the 3′ UTR. The binding of RBPs to these regions can increase or decrease the stability of an RNA molecule, depending on the specific RBP that binds.","{'ce0224fe-9431-43d0-8e14-e455e1c61d46': 'Binding of proteins to the RNA can also influence its stability. Proteins called RNA-binding proteins, or RBPs, can bind to the regions of the mRNA just upstream or downstream of the protein-coding region. These regions in the RNA that are not translated into protein are called the untranslated regions, or UTRs (figure 12.5). They are not introns (those have been removed in the nucleus). Rather, these are regions that regulate mRNA localization, stability, and protein translation. The region just before the protein-coding region is called the 5′ UTR, whereas the region after the coding region is called the 3′ UTR. The binding of RBPs to these regions can increase or decrease the stability of an RNA molecule, depending on the specific RBP that binds.', 'c29ed357-a44d-45fb-a8c0-a3f782fea4db': 'One classic example of this is the regulation of transferrin receptor (TR) and ferritin levels in response to iron.', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.6,cell_bio/images/Figure 12.6.jpg,Figure 12.6: Proteasome-mediated degradation.,"The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).","{'49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.1,cell_bio/images/Figure 12.1.jpg,Figure 12.1: Example of transcriptional complex involving two separate genes.,"Enhancer regions are binding sequences, or sites, for specific transcription factors. When a protein transcription factor binds to its enhancer sequence, the shape of the protein changes, allowing it to interact with proteins at the promotor site. However, since the enhancer region may be distant from the promoter, the DNA must bend to allow the proteins at the two sites to come into contact. DNA-bending proteins help bend the DNA and bring the enhancer and promoter regions together (figure 12.1). This shape change allows for the interaction of the specific activator proteins bound to the enhancers with the general transcription factors bound to the promoter region and the RNA polymerase. Two different genes may have the same promoter but different distal control elements, enabling differential gene expression.","{'367061fe-4d87-4a4d-b72b-297167a2fefc': 'Along with general transcription factors, there are additional regions that help increase or enhance transcription. These regions, called enhancers, are not necessarily close to the genes they enhance. They can be located upstream of a gene, within the coding region of the gene, downstream of a gene, or\xa0thousands of nucleotides away.', 'd5b65959-dc71-4f4e-8bb0-4a151b1b235a': 'Enhancer regions are binding sequences, or sites, for specific transcription factors. When a protein transcription factor binds to its enhancer sequence, the shape of the protein changes, allowing it to interact with proteins at the promotor site. However, since the enhancer region may be distant from the promoter, the DNA must bend to allow the proteins at the two sites to come into contact. DNA-bending proteins help bend the DNA and bring the enhancer and promoter regions together (figure 12.1). This shape change allows for the interaction of the specific activator proteins bound to the enhancers with the general transcription factors bound to the promoter region and the RNA polymerase. Two different genes may have the same promoter but different distal control elements, enabling differential gene expression.', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.2,cell_bio/images/Figure 12.2.jpg,Figure 12.2: Modification of DNA and histones can alter DNA accessibility and therefore transcription.,"Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptional repressors can bind to promoter or enhancer regions and block transcription. Like the transcriptional activators, repressors respond to external stimuli preventing the binding of activating transcription factors. This is often done by histone deacetylation, which increases the interaction of DNA and histones (figure 12.2).","{'6a3c0cfe-dbda-4ee9-8e2d-0b2c326af860': 'Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptional repressors can bind to promoter or enhancer regions and block transcription. Like the transcriptional activators, repressors respond to external stimuli preventing the binding of activating transcription factors. This is often done by histone deacetylation, which increases the interaction of DNA and histones (figure 12.2).', 'a022a82e-54e6-499b-ba54-bfdd54a06938': 'Structurally, transcription factors share similar characteristics but can take on very different secondary structures. Common examples of transcription factors include: Zn fingers, helix-loop-helixs, and leucine zippers. Regardless of structure, common characteristics include:', '6dca7235-56cb-43f1-9546-f97a92560741': 'As noted above, one of the major roles of transcription factors is to bend or remodel the DNA in a way to allow for interactions of transcription factors and their binding sites. Chromatin remodeling by modifications of the histones (through acetylation or shifting) is common (figure 12.2).', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.3,cell_bio/images/Figure 12.3.jpg,Figure 12.3: Five common modes of alternative splicing.,"Alternative RNA splicing is a mechanism that allows different protein products to be produced from one gene when different combinations of exons are combined to form the mRNA. This alternative splicing can be haphazard, but more often it is controlled and acts as a mechanism of gene regulation, with the frequency of different splicing alternatives controlled by the cell as a way to control the production of different protein products in different cells or at different stages of development. Alternative splicing is a common mechanism of gene regulation in eukaryotes; according to one estimate, 70 percent of genes in humans are expressed as multiple proteins through alternative splicing. Although there are multiple ways to alternatively splice RNA transcripts, the original 5′-3′ order of the exons is always conserved. That is, a transcript with exons 1 2 3 4 5 6 7 might be spliced 1 2 4 5 6 7 or 1 2 3 6 7, but never 1 2 5 4 3 6 7 (figure 12.3).","{'d6169e44-138e-4b82-a4fd-9cec550e51c5': 'Alternative RNA splicing is a mechanism that allows different protein products to be produced from one gene when different combinations of exons are combined to form the mRNA. This alternative splicing can be haphazard, but more often it is controlled and acts as a mechanism of gene regulation, with the frequency of different splicing alternatives controlled by the cell as a way to control the production of different protein products in different cells or at different stages of development. Alternative splicing is a common mechanism of gene regulation in eukaryotes; according to one estimate, 70 percent of genes in humans are expressed as multiple proteins through alternative splicing. Although there are multiple ways to alternatively splice RNA transcripts, the original 5′-3′ order of the exons is always conserved. That is, a transcript with exons 1 2 3 4 5 6 7 might be spliced 1 2 4 5 6 7 or 1 2 3 6 7, but never 1 2 5 4 3 6 7 (figure 12.3).', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.4,cell_bio/images/Figure 12.4.jpg,Figure 12.4: Regulation of translational initiation.,"The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly, and translation is impeded (figure 12.4).","{'37bdb907-a86b-4f97-ab65-584c9710c87a': 'In translation, the complex that assembles to start the process is referred to as the translation initiation complex, and similar to transcription, this complex can be activated or inhibited. In eukaryotes, translation is initiated by binding the initiating met-tRNAi to the 40S ribosome.', '926b42ec-c92b-44c7-97f6-44e2479f1895': 'Initially the met-tRNAi is brought to the 40S ribosome by a protein initiation factor, eukaryotic initiation factor-2 (eIF-2). The eIF-2 protein binds to the high-energy molecule guanosine triphosphate (GTP), and the tRNA-eIF2-GTP complex then binds to the 40S ribosome.', '770b9711-0232-40e8-ab64-40ee0d174bd2': 'The cap-binding protein eIF4F brings the mRNA complex together with the 40S ribosome complex. The ribosome then scans along the mRNA until it finds a start codon AUG. When the anticodon of the initiator tRNA and the start codon are aligned, the GTP is hydrolyzed, the initiation factors are released, and the large 60S ribosomal subunit binds to form the translation complex. Insulin increases the efficiency of formation of the cap-binding complex, therefore increasing the rate of protein synthesis.', '6688d9da-2c39-4d8d-be5d-63939d208064': 'The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly, and translation is impeded (figure 12.4).', '457442d7-5171-457c-9e5c-05c7bf133402': 'When eIF-2 remains unphosphorylated, the initiation complex can form normally, and translation can continue.', '2e4603d9-00fc-4d15-bf97-3255dbe2b61c': 'Translation is initiated by the assembly of the small ribosomal subunit (40S) with initiation factors (IF), which recognize the 5ʼ cap of the mRNA. This is referred to as the cap-binding complex, and this will scan the mRNA for the initial AUG needed to start translation. Once at the cap, the initiation complex tracks along the mRNA in the 5′ to 3′ direction, searching for the AUG start codon. Many eukaryotic mRNAs are translated from the first AUG, but this is not always the case. Once the appropriate AUG is identified, the other proteins and CBP dissociate, and the 60S subunit binds to the complex of Met-tRNAi, mRNA, and the 40S subunit. This step completes the initiation of translation in eukaryotes (figure 11.8).', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.5,cell_bio/images/Figure 12.5.jpg,Figure 12.5: RNA-Binding proteins can increase stability of the transcript.,"Binding of proteins to the RNA can also influence its stability. Proteins called RNA-binding proteins, or RBPs, can bind to the regions of the mRNA just upstream or downstream of the protein-coding region. These regions in the RNA that are not translated into protein are called the untranslated regions, or UTRs (figure 12.5). They are not introns (those have been removed in the nucleus). Rather, these are regions that regulate mRNA localization, stability, and protein translation. The region just before the protein-coding region is called the 5′ UTR, whereas the region after the coding region is called the 3′ UTR. The binding of RBPs to these regions can increase or decrease the stability of an RNA molecule, depending on the specific RBP that binds.","{'ce0224fe-9431-43d0-8e14-e455e1c61d46': 'Binding of proteins to the RNA can also influence its stability. Proteins called RNA-binding proteins, or RBPs, can bind to the regions of the mRNA just upstream or downstream of the protein-coding region. These regions in the RNA that are not translated into protein are called the untranslated regions, or UTRs (figure 12.5). They are not introns (those have been removed in the nucleus). Rather, these are regions that regulate mRNA localization, stability, and protein translation. The region just before the protein-coding region is called the 5′ UTR, whereas the region after the coding region is called the 3′ UTR. The binding of RBPs to these regions can increase or decrease the stability of an RNA molecule, depending on the specific RBP that binds.', 'c29ed357-a44d-45fb-a8c0-a3f782fea4db': 'One classic example of this is the regulation of transferrin receptor (TR) and ferritin levels in response to iron.', '49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).'}"
Figure 12.7,cell_bio/images/Figure 12.7.jpg,Figure 12.7: Overview of the cell cycle.,"The cycle is divided into four distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).","{'49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 12.8,cell_bio/images/Figure 12.8.jpg,Figure 12.8: Summary of the mitotic phase.,"To make two daughter cells, the contents of the nucleus and the cytoplasm must be divided. The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and moved to opposite poles of the cell, and then the cell is divided into two new identical daughter cells. The first portion of the mitotic phase, mitosis, is composed of five stages, which accomplish nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into two daughter cells (figure 12.8).","{'8edbac20-35c4-4c26-98c8-9c7ae612807b': 'To make two daughter cells, the contents of the nucleus and the cytoplasm must be divided. The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and moved to opposite poles of the cell, and then the cell is divided into two new identical daughter cells. The first portion of the mitotic phase, mitosis, is composed of five stages, which accomplish nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into two daughter cells (figure 12.8).', '5e1592ed-3c7f-4ab2-88c1-933406ae20e4': 'Mitosis is divided into a series of phases —\xa0prophase, prometaphase, metaphase, anaphase, and telophase —\xa0that result in the division of the cell nucleus (figure 12.8).', '6d23414b-b6e8-49a5-aebc-69cb7b88dbae': 'During prophase, the “first phase,” several events must occur to provide access to the chromosomes in the nucleus. The nuclear envelope starts to break into small vesicles, and the Golgi apparatus and endoplasmic reticulum fragment and disperse to the periphery of the cell. The nucleolus disappears. The centrosomes begin to move to opposite poles of the cell. The microtubules that form the basis of the mitotic spindle extend between the centrosomes, pushing them farther apart as the microtubule fibers lengthen. The sister chromatids begin to coil more tightly and become visible under a light microscope.', 'df5b2100-6271-4eb4-afc7-6a20a3fd09b5': 'During\xa0prometaphase, many processes that were begun in prophase continue to advance and culminate in the formation of a connection between the chromosomes and cytoskeleton. The remnants of the nuclear envelope disappear. The mitotic spindle continues to develop as more microtubules assemble and stretch across the length of the former nuclear area. Chromosomes become more condensed and visually discrete. Each sister chromatid attaches to spindle microtubules at the centromere via a protein complex called the kinetochore.', 'dbd33494-e584-45e0-a1c3-8d37c4e40577': 'During\xa0metaphase, all the chromosomes are aligned in a plane called the metaphase plate, or the equatorial plane, midway between the two poles of the cell. The sister chromatids are still tightly attached to each other. At this time, the chromosomes are maximally condensed.', 'bcceb08f-4e7a-418c-811e-cb84e7086a0c': 'During\xa0anaphase, the sister chromatids at the equatorial plane are split apart at the centromere. Each chromatid, now called a chromosome, is pulled rapidly toward the centrosome to which its microtubule was attached. The cell becomes visibly elongated as the nonkinetochore microtubules slide against each other at the metaphase plate where they overlap.', 'fb4cab6f-e65d-4230-99d9-c5ddea8e0da5': 'During\xa0telophase, all the events that set up the duplicated chromosomes for mitosis during the first three phases are reversed. The chromosomes reach the opposite poles and begin to decondense (unravel). The mitotic spindles are broken down into monomers that will be used to assemble cytoskeleton components for each daughter cell. Nuclear envelopes form around chromosomes.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 12.8,cell_bio/images/Figure 12.8.jpg,Figure 12.8: Summary of the mitotic phase.,"To make two daughter cells, the contents of the nucleus and the cytoplasm must be divided. The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and moved to opposite poles of the cell, and then the cell is divided into two new identical daughter cells. The first portion of the mitotic phase, mitosis, is composed of five stages, which accomplish nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into two daughter cells (figure 12.8).","{'8edbac20-35c4-4c26-98c8-9c7ae612807b': 'To make two daughter cells, the contents of the nucleus and the cytoplasm must be divided. The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and moved to opposite poles of the cell, and then the cell is divided into two new identical daughter cells. The first portion of the mitotic phase, mitosis, is composed of five stages, which accomplish nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into two daughter cells (figure 12.8).', '5e1592ed-3c7f-4ab2-88c1-933406ae20e4': 'Mitosis is divided into a series of phases —\xa0prophase, prometaphase, metaphase, anaphase, and telophase —\xa0that result in the division of the cell nucleus (figure 12.8).', '6d23414b-b6e8-49a5-aebc-69cb7b88dbae': 'During prophase, the “first phase,” several events must occur to provide access to the chromosomes in the nucleus. The nuclear envelope starts to break into small vesicles, and the Golgi apparatus and endoplasmic reticulum fragment and disperse to the periphery of the cell. The nucleolus disappears. The centrosomes begin to move to opposite poles of the cell. The microtubules that form the basis of the mitotic spindle extend between the centrosomes, pushing them farther apart as the microtubule fibers lengthen. The sister chromatids begin to coil more tightly and become visible under a light microscope.', 'df5b2100-6271-4eb4-afc7-6a20a3fd09b5': 'During\xa0prometaphase, many processes that were begun in prophase continue to advance and culminate in the formation of a connection between the chromosomes and cytoskeleton. The remnants of the nuclear envelope disappear. The mitotic spindle continues to develop as more microtubules assemble and stretch across the length of the former nuclear area. Chromosomes become more condensed and visually discrete. Each sister chromatid attaches to spindle microtubules at the centromere via a protein complex called the kinetochore.', 'dbd33494-e584-45e0-a1c3-8d37c4e40577': 'During\xa0metaphase, all the chromosomes are aligned in a plane called the metaphase plate, or the equatorial plane, midway between the two poles of the cell. The sister chromatids are still tightly attached to each other. At this time, the chromosomes are maximally condensed.', 'bcceb08f-4e7a-418c-811e-cb84e7086a0c': 'During\xa0anaphase, the sister chromatids at the equatorial plane are split apart at the centromere. Each chromatid, now called a chromosome, is pulled rapidly toward the centrosome to which its microtubule was attached. The cell becomes visibly elongated as the nonkinetochore microtubules slide against each other at the metaphase plate where they overlap.', 'fb4cab6f-e65d-4230-99d9-c5ddea8e0da5': 'During\xa0telophase, all the events that set up the duplicated chromosomes for mitosis during the first three phases are reversed. The chromosomes reach the opposite poles and begin to decondense (unravel). The mitotic spindles are broken down into monomers that will be used to assemble cytoskeleton components for each daughter cell. Nuclear envelopes form around chromosomes.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 12.9,cell_bio/images/Figure 12.9.jpg,Figure 12.9: Summary of cell cycle checkpoints and the role of CDK inhibitors in halting cell cycle progress.,"p21 will then act as a CDK inhibitor (Cip/Kip family) and blocks the action of the G1‒CDK complex. This will halt the cell cycle at the transition to the S1 phase, and the DNA can be repaired at leisure (figure 12.9). When this has been successfully completed, p53 is dephosphorylated, ubiquitinylated, and passed on to the proteasome. Thus, p53 does not accumulate in normal cells.","{'55f18151-12f7-40ec-8f7f-1b148f9ef178': 'During the process of DNA replication, DNA damage will halt the process until it can be repaired. Likewise, extrinsic damaging factors can trigger a DNA repair process. Protein p53 is commonly known\xa0for its role in DNA repair mechanisms. Under nonstressful conditions it is bound to mdm2 within the cytosol. In response to stress and DNA damage, it is activated, through ATM- or ATR-mediated phosphorylation. Once active, it functions as a transcription factor and induces the synthesis of protein p21.', 'f2e8c384-0600-4e06-9b4b-327a15ae0718': 'p21 will then act as a CDK inhibitor (Cip/Kip family) and blocks the action of the G1‒CDK complex. This will halt the cell cycle at the transition to the S1 phase, and the DNA can be repaired at leisure (figure 12.9). When this has been successfully completed, p53 is dephosphorylated, ubiquitinylated, and passed on to the proteasome. Thus, p53 does not accumulate in normal cells.', '7f75fdd9-ee93-43b0-ad35-38b63dc7deea': 'If the DNA repair systems do not succeed in eliminating the DNA damage, a steady increase in the concentration of phosphorylated p53 finally drives the cell into apoptosis. Proteins pRb and p53 are products of tumor suppressor genes. Complete absence of them, due to mutations, leads to accelerated cell division, a typical feature of tumors. In fact, somatic mutations in pRb and p53 have been found in more than half of all human tumors (figure 12.9).', '5ef01268-bfdf-490c-9ceb-d7b97ace660d': '12.2 References and resources', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 12.7,cell_bio/images/Figure 12.7.jpg,Figure 12.7: Overview of the cell cycle.,"The cycle is divided into four distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).","{'49f28104-4d8b-49d1-bb52-73d5564f3e1f': 'If proteins arenʼt folded properly, this can contribute to a host of disease processes related to misfolding events. Typically, folding is facilitated in the ER using chaperones (BiP), but if the protein is altered (due to mutation), this can lead to aggregation. Accumulation of BiP can initiate the unfolded protein response (UPR) (figure 17.3).', '7460cc39-4eee-4fe7-b5a0-2b07a41462f8': 'E3 ubiquitin ligase is often responsible for tagging aggregates with ubiquitin, which targets the protein to the proteasome. The proteasome consists of two subunits (19S and 20S) to make a functional 26S proteasome. Inside the proteasome, the polypeptide chains are cleaved back to their native amino acids and can be reused in other translational events. However, if the aggregates accumulate, in some instances they can contribute to any number of neurodegenerative disorders.', '3794a3e3-c6cf-4f6c-b61d-3e19dd563d82': 'The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded. One way to control gene expression, therefore, is to alter the longevity of the protein (figure 12.6).', 'c45d42b4-b37d-4e09-9420-5e386f5ad9f7': '12.1 References and resources', '8e38faa2-ffa1-42b4-b361-79ee84222f9a': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 10: Cell Reproduction, Chapter 11: Meiosis and Sexual Reproduction, Chapter 16: Gene Expression.', 'a1cc2d91-1fbd-4776-b83f-a5aa5a2a02f8': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication and Repair, Chapter 14: Cellular Reproduction.', '84c40167-03c9-4bbb-ad15-47c2d5d6bc7e': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 41–43, 46.', '7281b61b-11c4-44a4-8b85-a842014f125b': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 3: The Human Genome: Gene Structure and Function.', 'a6bfc2b0-7fae-4331-993d-b6e0ec27cf23': 'Lieberman M, Peet A. Figure 12.5 RNA Binding proteins can increase stability of the transcript. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 16.21 Translational regulation of ferritin synthesis. 2017.', '7a2fc746-978b-4cab-b62e-0cf020a0cc85': 'Lieberman M, Peet A. Figure 12.6 Proteasome mediated degradation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 312. Figure 35.6 The proteasome and regulatory proteins. 2017.', 'bf948ae2-98a1-4320-98c4-9598b5e1e1db': '12.2 Cell Cycle', '0cb860e9-a345-4ad5-943a-d712442cd199': 'Checkpoints are the most critical, and the full summary of mitosis is for background.', '6509939a-9391-4994-814f-948222d62374': 'The cycle is divided into four\xa0distinct phases, G1, S, G2, and M (mitosis), and for most mammalian cells in culture this process takes about twenty-four\xa0hours to complete. The majority of differentiated cells in the body are not dividing, retained in a resting state or Go (figure 12.7).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 12.8,cell_bio/images/Figure 12.8.jpg,Figure 12.8: Summary of the mitotic phase.,"To make two daughter cells, the contents of the nucleus and the cytoplasm must be divided. The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and moved to opposite poles of the cell, and then the cell is divided into two new identical daughter cells. The first portion of the mitotic phase, mitosis, is composed of five stages, which accomplish nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into two daughter cells (figure 12.8).","{'8edbac20-35c4-4c26-98c8-9c7ae612807b': 'To make two daughter cells, the contents of the nucleus and the cytoplasm must be divided. The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and moved to opposite poles of the cell, and then the cell is divided into two new identical daughter cells. The first portion of the mitotic phase, mitosis, is composed of five stages, which accomplish nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into two daughter cells (figure 12.8).', '5e1592ed-3c7f-4ab2-88c1-933406ae20e4': 'Mitosis is divided into a series of phases —\xa0prophase, prometaphase, metaphase, anaphase, and telophase —\xa0that result in the division of the cell nucleus (figure 12.8).', '6d23414b-b6e8-49a5-aebc-69cb7b88dbae': 'During prophase, the “first phase,” several events must occur to provide access to the chromosomes in the nucleus. The nuclear envelope starts to break into small vesicles, and the Golgi apparatus and endoplasmic reticulum fragment and disperse to the periphery of the cell. The nucleolus disappears. The centrosomes begin to move to opposite poles of the cell. The microtubules that form the basis of the mitotic spindle extend between the centrosomes, pushing them farther apart as the microtubule fibers lengthen. The sister chromatids begin to coil more tightly and become visible under a light microscope.', 'df5b2100-6271-4eb4-afc7-6a20a3fd09b5': 'During\xa0prometaphase, many processes that were begun in prophase continue to advance and culminate in the formation of a connection between the chromosomes and cytoskeleton. The remnants of the nuclear envelope disappear. The mitotic spindle continues to develop as more microtubules assemble and stretch across the length of the former nuclear area. Chromosomes become more condensed and visually discrete. Each sister chromatid attaches to spindle microtubules at the centromere via a protein complex called the kinetochore.', 'dbd33494-e584-45e0-a1c3-8d37c4e40577': 'During\xa0metaphase, all the chromosomes are aligned in a plane called the metaphase plate, or the equatorial plane, midway between the two poles of the cell. The sister chromatids are still tightly attached to each other. At this time, the chromosomes are maximally condensed.', 'bcceb08f-4e7a-418c-811e-cb84e7086a0c': 'During\xa0anaphase, the sister chromatids at the equatorial plane are split apart at the centromere. Each chromatid, now called a chromosome, is pulled rapidly toward the centrosome to which its microtubule was attached. The cell becomes visibly elongated as the nonkinetochore microtubules slide against each other at the metaphase plate where they overlap.', 'fb4cab6f-e65d-4230-99d9-c5ddea8e0da5': 'During\xa0telophase, all the events that set up the duplicated chromosomes for mitosis during the first three phases are reversed. The chromosomes reach the opposite poles and begin to decondense (unravel). The mitotic spindles are broken down into monomers that will be used to assemble cytoskeleton components for each daughter cell. Nuclear envelopes form around chromosomes.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 12.9,cell_bio/images/Figure 12.9.jpg,Figure 12.9: Summary of cell cycle checkpoints and the role of CDK inhibitors in halting cell cycle progress.,"p21 will then act as a CDK inhibitor (Cip/Kip family) and blocks the action of the G1‒CDK complex. This will halt the cell cycle at the transition to the S1 phase, and the DNA can be repaired at leisure (figure 12.9). When this has been successfully completed, p53 is dephosphorylated, ubiquitinylated, and passed on to the proteasome. Thus, p53 does not accumulate in normal cells.","{'55f18151-12f7-40ec-8f7f-1b148f9ef178': 'During the process of DNA replication, DNA damage will halt the process until it can be repaired. Likewise, extrinsic damaging factors can trigger a DNA repair process. Protein p53 is commonly known\xa0for its role in DNA repair mechanisms. Under nonstressful conditions it is bound to mdm2 within the cytosol. In response to stress and DNA damage, it is activated, through ATM- or ATR-mediated phosphorylation. Once active, it functions as a transcription factor and induces the synthesis of protein p21.', 'f2e8c384-0600-4e06-9b4b-327a15ae0718': 'p21 will then act as a CDK inhibitor (Cip/Kip family) and blocks the action of the G1‒CDK complex. This will halt the cell cycle at the transition to the S1 phase, and the DNA can be repaired at leisure (figure 12.9). When this has been successfully completed, p53 is dephosphorylated, ubiquitinylated, and passed on to the proteasome. Thus, p53 does not accumulate in normal cells.', '7f75fdd9-ee93-43b0-ad35-38b63dc7deea': 'If the DNA repair systems do not succeed in eliminating the DNA damage, a steady increase in the concentration of phosphorylated p53 finally drives the cell into apoptosis. Proteins pRb and p53 are products of tumor suppressor genes. Complete absence of them, due to mutations, leads to accelerated cell division, a typical feature of tumors. In fact, somatic mutations in pRb and p53 have been found in more than half of all human tumors (figure 12.9).', '5ef01268-bfdf-490c-9ceb-d7b97ace660d': '12.2 References and resources', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 12.10,cell_bio/images/Figure 12.10.jpg,Figure 12.10: Overview of meiosis.,"Meiosis is composed of two distinctive cell divisions, meiosis I and meiosis II, which are found only in the germline. Through these two divisions, haploid gametes are formed from diploid somatic cells. There is only one replication of the DNA, but there are two divisions of the chromosomes. The first division differs from the second in that there is pairing and recombination between homologous chromosomes resulting in variation in the genetic makeup of the gametes. Segregation of the homologues occurs during the first meiotic (reductional) division, reducing the forty-six chromosomes to twenty-three, one from each homologous pair. The second (equational) division is similar to mitosis with segregation of sister chromatids into daughter cells (figure 12.10).","{'27fbc03c-b817-48ce-a612-3ec33ef8793b': 'Meiosis is composed of two distinctive cell divisions,\xa0meiosis I and meiosis II, which\xa0are found only in the germline. Through these two divisions, haploid gametes are formed from diploid somatic cells. There is only one replication of the DNA, but there are two divisions of the chromosomes. The first division differs from the second in that there is pairing and recombination between homologous chromosomes resulting in variation in the genetic makeup of the gametes. Segregation of the homologues occurs during the first meiotic (reductional) division, reducing the forty-six\xa0chromosomes to twenty-three, one from each homologous pair. The second (equational) division is similar to mitosis with segregation of sister chromatids into daughter cells (figure 12.10).', '3d3fdbc3-4e5d-443b-b93a-a6eda82d7d56': 'Homologous pairing is unique to meiosis and plays two important roles: genetic recombination and chromosomal stabilization. While it has long been believed that the former is the most important, the latter is now accepted as the primary significance of meiotic recombination. During meiosis I, the pairing of homologues facilitates recombination, which is initiated by programed double-stranded breaks occurring at synaptic initiation sites (SISs). A subset of these breaks will resolve into the formation of the synaptonemal complex. When pairing is completed, synapsis occurs between the homologues, which completes the crossing over event. Each crossover event forms chasmata, which play an analogous role to the centromere and stabilize\xa0the maternal and paternal chromosomes. The stabilization of the metaphase chromosomes using this mechanism\xa0is key to normal chromosomal alignment and maintenance of an intact genome. Without recombination, the total number of unique gametic combinations of genes for each parent would be just over 8 million. However, crossing over greatly increases the total number of possible gene combinations such that the likelihood of either parent producing identical gametes is vanishingly small.', '1309681f-3c8e-49d6-ba7a-c59a43252048': '12.3 References and resources', 'f94bb9f9-35c2-47d4-9adc-5e0573663a03': 'The translation to protein is a bit more complex because three mRNA nucleotides correspond to one amino acid in the polypeptide sequence. However, the translation to protein is still systematic and colinear.'}"
Figure 12.10,cell_bio/images/Figure 12.10.jpg,Figure 12.10: Overview of meiosis.,"Meiosis is composed of two distinctive cell divisions, meiosis I and meiosis II, which are found only in the germline. Through these two divisions, haploid gametes are formed from diploid somatic cells. There is only one replication of the DNA, but there are two divisions of the chromosomes. The first division differs from the second in that there is pairing and recombination between homologous chromosomes resulting in variation in the genetic makeup of the gametes. Segregation of the homologues occurs during the first meiotic (reductional) division, reducing the forty-six chromosomes to twenty-three, one from each homologous pair. The second (equational) division is similar to mitosis with segregation of sister chromatids into daughter cells (figure 12.10).","{'27fbc03c-b817-48ce-a612-3ec33ef8793b': 'Meiosis is composed of two distinctive cell divisions,\xa0meiosis I and meiosis II, which\xa0are found only in the germline. Through these two divisions, haploid gametes are formed from diploid somatic cells. There is only one replication of the DNA, but there are two divisions of the chromosomes. The first division differs from the second in that there is pairing and recombination between homologous chromosomes resulting in variation in the genetic makeup of the gametes. Segregation of the homologues occurs during the first meiotic (reductional) division, reducing the forty-six\xa0chromosomes to twenty-three, one from each homologous pair. The second (equational) division is similar to mitosis with segregation of sister chromatids into daughter cells (figure 12.10).', '3d3fdbc3-4e5d-443b-b93a-a6eda82d7d56': 'Homologous pairing is unique to meiosis and plays two important roles: genetic recombination and chromosomal stabilization. While it has long been believed that the former is the most important, the latter is now accepted as the primary significance of meiotic recombination. During meiosis I, the pairing of homologues facilitates recombination, which is initiated by programed double-stranded breaks occurring at synaptic initiation sites (SISs). A subset of these breaks will resolve into the formation of the synaptonemal complex. When pairing is completed, synapsis occurs between the homologues, which completes the crossing over event. Each crossover event forms chasmata, which play an analogous role to the centromere and stabilize\xa0the maternal and paternal chromosomes. The stabilization of the metaphase chromosomes using this mechanism\xa0is key to normal chromosomal alignment and maintenance of an intact genome. Without recombination, the total number of unique gametic combinations of genes for each parent would be just over 8 million. However, crossing over greatly increases the total number of possible gene combinations such that the likelihood of either parent producing identical gametes is vanishingly small.', '1309681f-3c8e-49d6-ba7a-c59a43252048': '12.3 References and resources', 'f94bb9f9-35c2-47d4-9adc-5e0573663a03': 'The translation to protein is a bit more complex because three mRNA nucleotides correspond to one amino acid in the polypeptide sequence. However, the translation to protein is still systematic and colinear.'}"
Figure 11.2,cell_bio/images/Figure 11.2.jpg,Figure 11.2: Schematic view of a eukaryotic gene structure.,"The chromosome is organized into functional units call genes. These are specific locations on a chromosome that are composed of a transcribed region and a regulatory (or promoter) region. The transcribed region is typically (but not always) downstream of the transcriptional start and contains the following DNA elements: a 5ʼ cap site (required for maturation of mRNA), translational start (AUG), introns and exons, and the polyadenylation site (figure 11.2).","{'0e27dfb9-0315-4a9d-9e41-735d2af819bf': 'The chromosome is organized into functional units call genes. These are specific locations on a chromosome that are composed of a\xa0transcribed region and a regulatory (or promoter) region. The transcribed region is typically (but not always) downstream of the transcriptional start and contains the following DNA elements: a 5ʼ cap site (required for maturation of mRNA), translational start (AUG), introns and exons, and the polyadenylation site (figure 11.2).', '35f47e1d-6b9a-4c55-a578-7102e6bdf1b5': 'The regulatory or promoter region is upstream of the transcriptional start and contains regulatory elements such as:', '4fca3a38-aaa7-4277-81ba-b4ad4ea96cff': 'In eukaryotes, a single gene will produce one gene product as all genes are regulated independently. This is in contrast to prokaryotes, which regulate genes in an operon structure where one mRNA may be polycistronic and encode for multiple protein products.', 'd8bdf8ec-8eb5-4ca6-81e4-7d47bce1ff0a': 'rRNA, ribosomal RNA, is transcribed by RNA poly I and III and requires maturation that is slightly different from mRNA and tRNA. This RNA product is not translated but rather requires methylation and is incorporated into the protein as structural support. The 18S RNA is incorporated into the 40S ribosomal subunit, and the 28S, 5.8S, and 5S is incorporated into the 60S ribosomal subunit. These combine to make the full 80S ribosome required for protein translation.', '52437ade-a313-4fab-999b-96ba69ac2c34': '11.1 References and resources', 'eefc5cd9-c0fa-4183-baaf-7780657ec74b': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 15: Genes and Proteins.', 'a9ed0c94-6c1c-4844-a636-4550a0f102f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation.', 'bef1408e-e37f-4905-995a-37aa725ea289': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 39, 41–45.', 'ac84efbe-8779-466d-b0aa-55ea56c58b2c': 'Lieberman M, Peet A. Figure 11.1 Co-linearity of DNA and RNA. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 277. Figure 15.3 Reading frame of messenger RNA (mRNA). 2017.', '1cbf6cbb-3711-48d8-938b-f95db474684a': 'Lieberman M, Peet A. Figure 11.2 Schematic view of a eukaryotic gene structure. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 255. Figure 14.4 A schematic view of a eukarytoic gene, and steps required to produce a protein product. 2017. Added Myoglobin by AzaToth. Public domain. From Wikimedia Commons.', '8d4cb77f-7f72-4b2a-be0c-d69ce210a1bc': '11.2 Protein Translation', '966dd498-fc0e-412c-9c85-196e7ce837b9': 'Translation is the process by which mRNAs are converted into protein products through the interactions of mRNA, tRNA, and rRNA. Even before an mRNA is translated, a cell must invest energy to build each of its ribosomes, a complex macromolecule composed of structural and catalytic rRNAs, and many distinct polypeptides. In eukaryotes, the nucleolus is completely specialized for the synthesis and assembly of rRNAs.', '3808c5de-4ff8-4647-8c5f-e05e084f6753': 'Ribosomes exist in the cytoplasm and rough endoplasmic reticulum of eukaryotes. Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation.', '8b79b097-d0ac-4a62-b605-e236e472f0bc': 'Each mRNA molecule is simultaneously translated by many ribosomes, all synthesizing protein in the same direction: reading the mRNA from 5′ to 3′ and synthesizing the polypeptide from the N terminus to the C terminus. The complete mRNA/poly-ribosome structure is called a polysome.'}"
Figure 11.3,cell_bio/images/Figure 11.3.jpg,Figure 11.3: Transcription initiation.,"Transcription factors that bind to the promoter are called basal transcription factors. These basal factors are all called TFII (for transcription factor/polymerase II) plus an additional letter (A–J). The core complex is TFIID, which includes a TATA-binding protein (TBP). The other transcription factors systematically fall into place on the DNA template, with each one further stabilizing the pre-initiation complex and contributing to the recruitment of RNA polymerase II (figure 11.3).","{'e1552d45-0186-433a-aa7a-aec1e8f1cbf0': 'Eukaryotes assemble a complex of transcription factors required to recruit RNA polymerase II to a protein coding gene.', 'e40aab1b-ac80-40cd-af2e-44681ecda242': 'Transcription factors that bind to the promoter are called basal transcription factors. These basal factors are all called TFII (for transcription factor/polymerase II) plus an additional letter (A–J). The core complex is TFIID, which includes a TATA-binding protein (TBP). The other transcription factors systematically fall into place on the DNA template, with each one further stabilizing the pre-initiation complex and contributing to the recruitment of RNA polymerase II (figure 11.3).', '949751dd-86ff-4c0f-823d-3d6a3850fc2c': 'Some eukaryotic promoters also have a conserved CAAT box (GGCCAATCT) at approximately -80. Further upstream of the TATA box, eukaryotic promoters may also contain one or more GC-rich boxes (GGCG) or octamer boxes (ATTTGCAT). These elements bind cellular factors that increase the efficiency of transcription initiation and are often identified in more “active” genes that are constantly being expressed by the cell. Other regulatory elements within the promoter region will be discussed in section 12.1.', 'd8bdf8ec-8eb5-4ca6-81e4-7d47bce1ff0a': 'rRNA, ribosomal RNA, is transcribed by RNA poly I and III and requires maturation that is slightly different from mRNA and tRNA. This RNA product is not translated but rather requires methylation and is incorporated into the protein as structural support. The 18S RNA is incorporated into the 40S ribosomal subunit, and the 28S, 5.8S, and 5S is incorporated into the 60S ribosomal subunit. These combine to make the full 80S ribosome required for protein translation.', '52437ade-a313-4fab-999b-96ba69ac2c34': '11.1 References and resources', 'eefc5cd9-c0fa-4183-baaf-7780657ec74b': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 15: Genes and Proteins.', 'a9ed0c94-6c1c-4844-a636-4550a0f102f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation.', 'bef1408e-e37f-4905-995a-37aa725ea289': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 39, 41–45.', 'ac84efbe-8779-466d-b0aa-55ea56c58b2c': 'Lieberman M, Peet A. Figure 11.1 Co-linearity of DNA and RNA. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 277. Figure 15.3 Reading frame of messenger RNA (mRNA). 2017.', '1cbf6cbb-3711-48d8-938b-f95db474684a': 'Lieberman M, Peet A. Figure 11.2 Schematic view of a eukaryotic gene structure. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 255. Figure 14.4 A schematic view of a eukarytoic gene, and steps required to produce a protein product. 2017. Added Myoglobin by AzaToth. Public domain. From Wikimedia Commons.', '8d4cb77f-7f72-4b2a-be0c-d69ce210a1bc': '11.2 Protein Translation', '966dd498-fc0e-412c-9c85-196e7ce837b9': 'Translation is the process by which mRNAs are converted into protein products through the interactions of mRNA, tRNA, and rRNA. Even before an mRNA is translated, a cell must invest energy to build each of its ribosomes, a complex macromolecule composed of structural and catalytic rRNAs, and many distinct polypeptides. In eukaryotes, the nucleolus is completely specialized for the synthesis and assembly of rRNAs.', '3808c5de-4ff8-4647-8c5f-e05e084f6753': 'Ribosomes exist in the cytoplasm and rough endoplasmic reticulum of eukaryotes. Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation.', '8b79b097-d0ac-4a62-b605-e236e472f0bc': 'Each mRNA molecule is simultaneously translated by many ribosomes, all synthesizing protein in the same direction: reading the mRNA from 5′ to 3′ and synthesizing the polypeptide from the N terminus to the C terminus. The complete mRNA/poly-ribosome structure is called a polysome.'}"
Figure 11.4,cell_bio/images/Figure 11.4.jpg,Figure 11.4: Overview of mRNA processing involving the removal of introns (splicing) and the addition of a 5’ cap and 3’ tail.,"In eukaryotes, pre-mRNA requires maturation before use in translation including (figure 11.4):","{'b44be84e-566e-4fc4-b080-080a6cf6f45f': 'In eukaryotes, pre-mRNA requires maturation before use in translation including (figure 11.4):', 'f6be0f92-36d2-4858-9605-8073fe52e152': 'Splicing is a complex process mediated by a large protein RNA-associated complex called the spliceosome. The structure contains both proteins and small nuclear (sn)RNA. (Note antibodies to snRNAs are specific for systemic lupus.)\xa0Intronic sequences usually have GU at their 5′ end and AG at their 3′ end. An adenosine (A) is typically found at the branching point within the intron sequence. Small nuclear ribonucleoproteins (snRNPs) of the spliceosome recognize intron‒exon junctions and splice out the intron as a “lariat” structure. Splicing starts with an autocatalytic cleavage of the 5ʼ end of the intron leading to the formation of a circular or lariat\xa0where\xa0a 5′\xa0UG sequence pairs with an internal adenine (A) or branch site. Finally the 3ʼ end of the intron is cleaved, and the intron is released as a lariat, and the right side of the exon is spliced to the left side. Alternative splicing of introns and exons generates protein variation from a single mRNA (figure 11.5).', 'd8bdf8ec-8eb5-4ca6-81e4-7d47bce1ff0a': 'rRNA, ribosomal RNA, is transcribed by RNA poly I and III and requires maturation that is slightly different from mRNA and tRNA. This RNA product is not translated but rather requires methylation and is incorporated into the protein as structural support. The 18S RNA is incorporated into the 40S ribosomal subunit, and the 28S, 5.8S, and 5S is incorporated into the 60S ribosomal subunit. These combine to make the full 80S ribosome required for protein translation.', '52437ade-a313-4fab-999b-96ba69ac2c34': '11.1 References and resources', 'eefc5cd9-c0fa-4183-baaf-7780657ec74b': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 15: Genes and Proteins.', 'a9ed0c94-6c1c-4844-a636-4550a0f102f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation.', 'bef1408e-e37f-4905-995a-37aa725ea289': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 39, 41–45.', 'ac84efbe-8779-466d-b0aa-55ea56c58b2c': 'Lieberman M, Peet A. Figure 11.1 Co-linearity of DNA and RNA. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 277. Figure 15.3 Reading frame of messenger RNA (mRNA). 2017.', '1cbf6cbb-3711-48d8-938b-f95db474684a': 'Lieberman M, Peet A. Figure 11.2 Schematic view of a eukaryotic gene structure. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 255. Figure 14.4 A schematic view of a eukarytoic gene, and steps required to produce a protein product. 2017. Added Myoglobin by AzaToth. Public domain. From Wikimedia Commons.', '8d4cb77f-7f72-4b2a-be0c-d69ce210a1bc': '11.2 Protein Translation', '966dd498-fc0e-412c-9c85-196e7ce837b9': 'Translation is the process by which mRNAs are converted into protein products through the interactions of mRNA, tRNA, and rRNA. Even before an mRNA is translated, a cell must invest energy to build each of its ribosomes, a complex macromolecule composed of structural and catalytic rRNAs, and many distinct polypeptides. In eukaryotes, the nucleolus is completely specialized for the synthesis and assembly of rRNAs.', '3808c5de-4ff8-4647-8c5f-e05e084f6753': 'Ribosomes exist in the cytoplasm and rough endoplasmic reticulum of eukaryotes. Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation.', '8b79b097-d0ac-4a62-b605-e236e472f0bc': 'Each mRNA molecule is simultaneously translated by many ribosomes, all synthesizing protein in the same direction: reading the mRNA from 5′ to 3′ and synthesizing the polypeptide from the N terminus to the C terminus. The complete mRNA/poly-ribosome structure is called a polysome.'}"
Figure 11.5,cell_bio/images/Figure 11.5.jpg,Figure 11.5: Summary of mRNA splicing.,"Splicing is a complex process mediated by a large protein RNA-associated complex called the spliceosome. The structure contains both proteins and small nuclear (sn)RNA. (Note antibodies to snRNAs are specific for systemic lupus.) Intronic sequences usually have GU at their 5′ end and AG at their 3′ end. An adenosine (A) is typically found at the branching point within the intron sequence. Small nuclear ribonucleoproteins (snRNPs) of the spliceosome recognize intron‒exon junctions and splice out the intron as a “lariat” structure. Splicing starts with an autocatalytic cleavage of the 5ʼ end of the intron leading to the formation of a circular or lariat where a 5′ UG sequence pairs with an internal adenine (A) or branch site. Finally the 3ʼ end of the intron is cleaved, and the intron is released as a lariat, and the right side of the exon is spliced to the left side. Alternative splicing of introns and exons generates protein variation from a single mRNA (figure 11.5).","{'b44be84e-566e-4fc4-b080-080a6cf6f45f': 'In eukaryotes, pre-mRNA requires maturation before use in translation including (figure 11.4):', 'f6be0f92-36d2-4858-9605-8073fe52e152': 'Splicing is a complex process mediated by a large protein RNA-associated complex called the spliceosome. The structure contains both proteins and small nuclear (sn)RNA. (Note antibodies to snRNAs are specific for systemic lupus.)\xa0Intronic sequences usually have GU at their 5′ end and AG at their 3′ end. An adenosine (A) is typically found at the branching point within the intron sequence. Small nuclear ribonucleoproteins (snRNPs) of the spliceosome recognize intron‒exon junctions and splice out the intron as a “lariat” structure. Splicing starts with an autocatalytic cleavage of the 5ʼ end of the intron leading to the formation of a circular or lariat\xa0where\xa0a 5′\xa0UG sequence pairs with an internal adenine (A) or branch site. Finally the 3ʼ end of the intron is cleaved, and the intron is released as a lariat, and the right side of the exon is spliced to the left side. Alternative splicing of introns and exons generates protein variation from a single mRNA (figure 11.5).', 'd8bdf8ec-8eb5-4ca6-81e4-7d47bce1ff0a': 'rRNA, ribosomal RNA, is transcribed by RNA poly I and III and requires maturation that is slightly different from mRNA and tRNA. This RNA product is not translated but rather requires methylation and is incorporated into the protein as structural support. The 18S RNA is incorporated into the 40S ribosomal subunit, and the 28S, 5.8S, and 5S is incorporated into the 60S ribosomal subunit. These combine to make the full 80S ribosome required for protein translation.', '52437ade-a313-4fab-999b-96ba69ac2c34': '11.1 References and resources', 'eefc5cd9-c0fa-4183-baaf-7780657ec74b': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 15: Genes and Proteins.', 'a9ed0c94-6c1c-4844-a636-4550a0f102f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation.', 'bef1408e-e37f-4905-995a-37aa725ea289': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 39, 41–45.', 'ac84efbe-8779-466d-b0aa-55ea56c58b2c': 'Lieberman M, Peet A. Figure 11.1 Co-linearity of DNA and RNA. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 277. Figure 15.3 Reading frame of messenger RNA (mRNA). 2017.', '1cbf6cbb-3711-48d8-938b-f95db474684a': 'Lieberman M, Peet A. Figure 11.2 Schematic view of a eukaryotic gene structure. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 255. Figure 14.4 A schematic view of a eukarytoic gene, and steps required to produce a protein product. 2017. Added Myoglobin by AzaToth. Public domain. From Wikimedia Commons.', '8d4cb77f-7f72-4b2a-be0c-d69ce210a1bc': '11.2 Protein Translation', '966dd498-fc0e-412c-9c85-196e7ce837b9': 'Translation is the process by which mRNAs are converted into protein products through the interactions of mRNA, tRNA, and rRNA. Even before an mRNA is translated, a cell must invest energy to build each of its ribosomes, a complex macromolecule composed of structural and catalytic rRNAs, and many distinct polypeptides. In eukaryotes, the nucleolus is completely specialized for the synthesis and assembly of rRNAs.', '3808c5de-4ff8-4647-8c5f-e05e084f6753': 'Ribosomes exist in the cytoplasm and rough endoplasmic reticulum of eukaryotes. Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation.', '8b79b097-d0ac-4a62-b605-e236e472f0bc': 'Each mRNA molecule is simultaneously translated by many ribosomes, all synthesizing protein in the same direction: reading the mRNA from 5′ to 3′ and synthesizing the polypeptide from the N terminus to the C terminus. The complete mRNA/poly-ribosome structure is called a polysome.'}"
Figure 11.3,cell_bio/images/Figure 11.3.jpg,Figure 11.3: Transcription initiation.,"Transcription factors that bind to the promoter are called basal transcription factors. These basal factors are all called TFII (for transcription factor/polymerase II) plus an additional letter (A–J). The core complex is TFIID, which includes a TATA-binding protein (TBP). The other transcription factors systematically fall into place on the DNA template, with each one further stabilizing the pre-initiation complex and contributing to the recruitment of RNA polymerase II (figure 11.3).","{'e1552d45-0186-433a-aa7a-aec1e8f1cbf0': 'Eukaryotes assemble a complex of transcription factors required to recruit RNA polymerase II to a protein coding gene.', 'e40aab1b-ac80-40cd-af2e-44681ecda242': 'Transcription factors that bind to the promoter are called basal transcription factors. These basal factors are all called TFII (for transcription factor/polymerase II) plus an additional letter (A–J). The core complex is TFIID, which includes a TATA-binding protein (TBP). The other transcription factors systematically fall into place on the DNA template, with each one further stabilizing the pre-initiation complex and contributing to the recruitment of RNA polymerase II (figure 11.3).', '949751dd-86ff-4c0f-823d-3d6a3850fc2c': 'Some eukaryotic promoters also have a conserved CAAT box (GGCCAATCT) at approximately -80. Further upstream of the TATA box, eukaryotic promoters may also contain one or more GC-rich boxes (GGCG) or octamer boxes (ATTTGCAT). These elements bind cellular factors that increase the efficiency of transcription initiation and are often identified in more “active” genes that are constantly being expressed by the cell. Other regulatory elements within the promoter region will be discussed in section 12.1.', 'd8bdf8ec-8eb5-4ca6-81e4-7d47bce1ff0a': 'rRNA, ribosomal RNA, is transcribed by RNA poly I and III and requires maturation that is slightly different from mRNA and tRNA. This RNA product is not translated but rather requires methylation and is incorporated into the protein as structural support. The 18S RNA is incorporated into the 40S ribosomal subunit, and the 28S, 5.8S, and 5S is incorporated into the 60S ribosomal subunit. These combine to make the full 80S ribosome required for protein translation.', '52437ade-a313-4fab-999b-96ba69ac2c34': '11.1 References and resources', 'eefc5cd9-c0fa-4183-baaf-7780657ec74b': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 15: Genes and Proteins.', 'a9ed0c94-6c1c-4844-a636-4550a0f102f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation.', 'bef1408e-e37f-4905-995a-37aa725ea289': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 39, 41–45.', 'ac84efbe-8779-466d-b0aa-55ea56c58b2c': 'Lieberman M, Peet A. Figure 11.1 Co-linearity of DNA and RNA. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 277. Figure 15.3 Reading frame of messenger RNA (mRNA). 2017.', '1cbf6cbb-3711-48d8-938b-f95db474684a': 'Lieberman M, Peet A. Figure 11.2 Schematic view of a eukaryotic gene structure. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 255. Figure 14.4 A schematic view of a eukarytoic gene, and steps required to produce a protein product. 2017. Added Myoglobin by AzaToth. Public domain. From Wikimedia Commons.', '8d4cb77f-7f72-4b2a-be0c-d69ce210a1bc': '11.2 Protein Translation', '966dd498-fc0e-412c-9c85-196e7ce837b9': 'Translation is the process by which mRNAs are converted into protein products through the interactions of mRNA, tRNA, and rRNA. Even before an mRNA is translated, a cell must invest energy to build each of its ribosomes, a complex macromolecule composed of structural and catalytic rRNAs, and many distinct polypeptides. In eukaryotes, the nucleolus is completely specialized for the synthesis and assembly of rRNAs.', '3808c5de-4ff8-4647-8c5f-e05e084f6753': 'Ribosomes exist in the cytoplasm and rough endoplasmic reticulum of eukaryotes. Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation.', '8b79b097-d0ac-4a62-b605-e236e472f0bc': 'Each mRNA molecule is simultaneously translated by many ribosomes, all synthesizing protein in the same direction: reading the mRNA from 5′ to 3′ and synthesizing the polypeptide from the N terminus to the C terminus. The complete mRNA/poly-ribosome structure is called a polysome.'}"
Figure 11.4,cell_bio/images/Figure 11.4.jpg,Figure 11.4: Overview of mRNA processing involving the removal of introns (splicing) and the addition of a 5’ cap and 3’ tail.,"In eukaryotes, pre-mRNA requires maturation before use in translation including (figure 11.4):","{'b44be84e-566e-4fc4-b080-080a6cf6f45f': 'In eukaryotes, pre-mRNA requires maturation before use in translation including (figure 11.4):', 'f6be0f92-36d2-4858-9605-8073fe52e152': 'Splicing is a complex process mediated by a large protein RNA-associated complex called the spliceosome. The structure contains both proteins and small nuclear (sn)RNA. (Note antibodies to snRNAs are specific for systemic lupus.)\xa0Intronic sequences usually have GU at their 5′ end and AG at their 3′ end. An adenosine (A) is typically found at the branching point within the intron sequence. Small nuclear ribonucleoproteins (snRNPs) of the spliceosome recognize intron‒exon junctions and splice out the intron as a “lariat” structure. Splicing starts with an autocatalytic cleavage of the 5ʼ end of the intron leading to the formation of a circular or lariat\xa0where\xa0a 5′\xa0UG sequence pairs with an internal adenine (A) or branch site. Finally the 3ʼ end of the intron is cleaved, and the intron is released as a lariat, and the right side of the exon is spliced to the left side. Alternative splicing of introns and exons generates protein variation from a single mRNA (figure 11.5).', 'd8bdf8ec-8eb5-4ca6-81e4-7d47bce1ff0a': 'rRNA, ribosomal RNA, is transcribed by RNA poly I and III and requires maturation that is slightly different from mRNA and tRNA. This RNA product is not translated but rather requires methylation and is incorporated into the protein as structural support. The 18S RNA is incorporated into the 40S ribosomal subunit, and the 28S, 5.8S, and 5S is incorporated into the 60S ribosomal subunit. These combine to make the full 80S ribosome required for protein translation.', '52437ade-a313-4fab-999b-96ba69ac2c34': '11.1 References and resources', 'eefc5cd9-c0fa-4183-baaf-7780657ec74b': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 15: Genes and Proteins.', 'a9ed0c94-6c1c-4844-a636-4550a0f102f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation.', 'bef1408e-e37f-4905-995a-37aa725ea289': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 39, 41–45.', 'ac84efbe-8779-466d-b0aa-55ea56c58b2c': 'Lieberman M, Peet A. Figure 11.1 Co-linearity of DNA and RNA. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 277. Figure 15.3 Reading frame of messenger RNA (mRNA). 2017.', '1cbf6cbb-3711-48d8-938b-f95db474684a': 'Lieberman M, Peet A. Figure 11.2 Schematic view of a eukaryotic gene structure. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 255. Figure 14.4 A schematic view of a eukarytoic gene, and steps required to produce a protein product. 2017. Added Myoglobin by AzaToth. Public domain. From Wikimedia Commons.', '8d4cb77f-7f72-4b2a-be0c-d69ce210a1bc': '11.2 Protein Translation', '966dd498-fc0e-412c-9c85-196e7ce837b9': 'Translation is the process by which mRNAs are converted into protein products through the interactions of mRNA, tRNA, and rRNA. Even before an mRNA is translated, a cell must invest energy to build each of its ribosomes, a complex macromolecule composed of structural and catalytic rRNAs, and many distinct polypeptides. In eukaryotes, the nucleolus is completely specialized for the synthesis and assembly of rRNAs.', '3808c5de-4ff8-4647-8c5f-e05e084f6753': 'Ribosomes exist in the cytoplasm and rough endoplasmic reticulum of eukaryotes. Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation.', '8b79b097-d0ac-4a62-b605-e236e472f0bc': 'Each mRNA molecule is simultaneously translated by many ribosomes, all synthesizing protein in the same direction: reading the mRNA from 5′ to 3′ and synthesizing the polypeptide from the N terminus to the C terminus. The complete mRNA/poly-ribosome structure is called a polysome.'}"
Figure 11.5,cell_bio/images/Figure 11.5.jpg,Figure 11.5: Summary of mRNA splicing.,"Splicing is a complex process mediated by a large protein RNA-associated complex called the spliceosome. The structure contains both proteins and small nuclear (sn)RNA. (Note antibodies to snRNAs are specific for systemic lupus.) Intronic sequences usually have GU at their 5′ end and AG at their 3′ end. An adenosine (A) is typically found at the branching point within the intron sequence. Small nuclear ribonucleoproteins (snRNPs) of the spliceosome recognize intron‒exon junctions and splice out the intron as a “lariat” structure. Splicing starts with an autocatalytic cleavage of the 5ʼ end of the intron leading to the formation of a circular or lariat where a 5′ UG sequence pairs with an internal adenine (A) or branch site. Finally the 3ʼ end of the intron is cleaved, and the intron is released as a lariat, and the right side of the exon is spliced to the left side. Alternative splicing of introns and exons generates protein variation from a single mRNA (figure 11.5).","{'b44be84e-566e-4fc4-b080-080a6cf6f45f': 'In eukaryotes, pre-mRNA requires maturation before use in translation including (figure 11.4):', 'f6be0f92-36d2-4858-9605-8073fe52e152': 'Splicing is a complex process mediated by a large protein RNA-associated complex called the spliceosome. The structure contains both proteins and small nuclear (sn)RNA. (Note antibodies to snRNAs are specific for systemic lupus.)\xa0Intronic sequences usually have GU at their 5′ end and AG at their 3′ end. An adenosine (A) is typically found at the branching point within the intron sequence. Small nuclear ribonucleoproteins (snRNPs) of the spliceosome recognize intron‒exon junctions and splice out the intron as a “lariat” structure. Splicing starts with an autocatalytic cleavage of the 5ʼ end of the intron leading to the formation of a circular or lariat\xa0where\xa0a 5′\xa0UG sequence pairs with an internal adenine (A) or branch site. Finally the 3ʼ end of the intron is cleaved, and the intron is released as a lariat, and the right side of the exon is spliced to the left side. Alternative splicing of introns and exons generates protein variation from a single mRNA (figure 11.5).', 'd8bdf8ec-8eb5-4ca6-81e4-7d47bce1ff0a': 'rRNA, ribosomal RNA, is transcribed by RNA poly I and III and requires maturation that is slightly different from mRNA and tRNA. This RNA product is not translated but rather requires methylation and is incorporated into the protein as structural support. The 18S RNA is incorporated into the 40S ribosomal subunit, and the 28S, 5.8S, and 5S is incorporated into the 60S ribosomal subunit. These combine to make the full 80S ribosome required for protein translation.', '52437ade-a313-4fab-999b-96ba69ac2c34': '11.1 References and resources', 'eefc5cd9-c0fa-4183-baaf-7780657ec74b': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 15: Genes and Proteins.', 'a9ed0c94-6c1c-4844-a636-4550a0f102f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation.', 'bef1408e-e37f-4905-995a-37aa725ea289': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 39, 41–45.', 'ac84efbe-8779-466d-b0aa-55ea56c58b2c': 'Lieberman M, Peet A. Figure 11.1 Co-linearity of DNA and RNA. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 277. Figure 15.3 Reading frame of messenger RNA (mRNA). 2017.', '1cbf6cbb-3711-48d8-938b-f95db474684a': 'Lieberman M, Peet A. Figure 11.2 Schematic view of a eukaryotic gene structure. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 255. Figure 14.4 A schematic view of a eukarytoic gene, and steps required to produce a protein product. 2017. Added Myoglobin by AzaToth. Public domain. From Wikimedia Commons.', '8d4cb77f-7f72-4b2a-be0c-d69ce210a1bc': '11.2 Protein Translation', '966dd498-fc0e-412c-9c85-196e7ce837b9': 'Translation is the process by which mRNAs are converted into protein products through the interactions of mRNA, tRNA, and rRNA. Even before an mRNA is translated, a cell must invest energy to build each of its ribosomes, a complex macromolecule composed of structural and catalytic rRNAs, and many distinct polypeptides. In eukaryotes, the nucleolus is completely specialized for the synthesis and assembly of rRNAs.', '3808c5de-4ff8-4647-8c5f-e05e084f6753': 'Ribosomes exist in the cytoplasm and rough endoplasmic reticulum of eukaryotes. Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation.', '8b79b097-d0ac-4a62-b605-e236e472f0bc': 'Each mRNA molecule is simultaneously translated by many ribosomes, all synthesizing protein in the same direction: reading the mRNA from 5′ to 3′ and synthesizing the polypeptide from the N terminus to the C terminus. The complete mRNA/poly-ribosome structure is called a polysome.'}"
Figure 11.1,cell_bio/images/Figure 11.1.jpg,Figure 11.1: Colinearity of DNA and RNA.,"Lieberman M, Peet A. Figure 11.1 Co-linearity of DNA and RNA. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 277. Figure 15.3 Reading frame of messenger RNA (mRNA). 2017.","{'d8bdf8ec-8eb5-4ca6-81e4-7d47bce1ff0a': 'rRNA, ribosomal RNA, is transcribed by RNA poly I and III and requires maturation that is slightly different from mRNA and tRNA. This RNA product is not translated but rather requires methylation and is incorporated into the protein as structural support. The 18S RNA is incorporated into the 40S ribosomal subunit, and the 28S, 5.8S, and 5S is incorporated into the 60S ribosomal subunit. These combine to make the full 80S ribosome required for protein translation.', '52437ade-a313-4fab-999b-96ba69ac2c34': '11.1 References and resources', 'eefc5cd9-c0fa-4183-baaf-7780657ec74b': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 15: Genes and Proteins.', 'a9ed0c94-6c1c-4844-a636-4550a0f102f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation.', 'bef1408e-e37f-4905-995a-37aa725ea289': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 39, 41–45.', 'ac84efbe-8779-466d-b0aa-55ea56c58b2c': 'Lieberman M, Peet A. Figure 11.1 Co-linearity of DNA and RNA. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 277. Figure 15.3 Reading frame of messenger RNA (mRNA). 2017.', '1cbf6cbb-3711-48d8-938b-f95db474684a': 'Lieberman M, Peet A. Figure 11.2 Schematic view of a eukaryotic gene structure. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 255. Figure 14.4 A schematic view of a eukarytoic gene, and steps required to produce a protein product. 2017. Added Myoglobin by AzaToth. Public domain. From Wikimedia Commons.', '8d4cb77f-7f72-4b2a-be0c-d69ce210a1bc': '11.2 Protein Translation', '966dd498-fc0e-412c-9c85-196e7ce837b9': 'Translation is the process by which mRNAs are converted into protein products through the interactions of mRNA, tRNA, and rRNA. Even before an mRNA is translated, a cell must invest energy to build each of its ribosomes, a complex macromolecule composed of structural and catalytic rRNAs, and many distinct polypeptides. In eukaryotes, the nucleolus is completely specialized for the synthesis and assembly of rRNAs.', '3808c5de-4ff8-4647-8c5f-e05e084f6753': 'Ribosomes exist in the cytoplasm and rough endoplasmic reticulum of eukaryotes. Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation.', '8b79b097-d0ac-4a62-b605-e236e472f0bc': 'Each mRNA molecule is simultaneously translated by many ribosomes, all synthesizing protein in the same direction: reading the mRNA from 5′ to 3′ and synthesizing the polypeptide from the N terminus to the C terminus. The complete mRNA/poly-ribosome structure is called a polysome.'}"
Figure 11.2,cell_bio/images/Figure 11.2.jpg,Figure 11.2: Schematic view of a eukaryotic gene structure.,"The chromosome is organized into functional units call genes. These are specific locations on a chromosome that are composed of a transcribed region and a regulatory (or promoter) region. The transcribed region is typically (but not always) downstream of the transcriptional start and contains the following DNA elements: a 5ʼ cap site (required for maturation of mRNA), translational start (AUG), introns and exons, and the polyadenylation site (figure 11.2).","{'0e27dfb9-0315-4a9d-9e41-735d2af819bf': 'The chromosome is organized into functional units call genes. These are specific locations on a chromosome that are composed of a\xa0transcribed region and a regulatory (or promoter) region. The transcribed region is typically (but not always) downstream of the transcriptional start and contains the following DNA elements: a 5ʼ cap site (required for maturation of mRNA), translational start (AUG), introns and exons, and the polyadenylation site (figure 11.2).', '35f47e1d-6b9a-4c55-a578-7102e6bdf1b5': 'The regulatory or promoter region is upstream of the transcriptional start and contains regulatory elements such as:', '4fca3a38-aaa7-4277-81ba-b4ad4ea96cff': 'In eukaryotes, a single gene will produce one gene product as all genes are regulated independently. This is in contrast to prokaryotes, which regulate genes in an operon structure where one mRNA may be polycistronic and encode for multiple protein products.', 'd8bdf8ec-8eb5-4ca6-81e4-7d47bce1ff0a': 'rRNA, ribosomal RNA, is transcribed by RNA poly I and III and requires maturation that is slightly different from mRNA and tRNA. This RNA product is not translated but rather requires methylation and is incorporated into the protein as structural support. The 18S RNA is incorporated into the 40S ribosomal subunit, and the 28S, 5.8S, and 5S is incorporated into the 60S ribosomal subunit. These combine to make the full 80S ribosome required for protein translation.', '52437ade-a313-4fab-999b-96ba69ac2c34': '11.1 References and resources', 'eefc5cd9-c0fa-4183-baaf-7780657ec74b': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 15: Genes and Proteins.', 'a9ed0c94-6c1c-4844-a636-4550a0f102f2': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 11: Gene Expression: From Transcription to Translation.', 'bef1408e-e37f-4905-995a-37aa725ea289': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 39, 41–45.', 'ac84efbe-8779-466d-b0aa-55ea56c58b2c': 'Lieberman M, Peet A. Figure 11.1 Co-linearity of DNA and RNA. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 277. Figure 15.3 Reading frame of messenger RNA (mRNA). 2017.', '1cbf6cbb-3711-48d8-938b-f95db474684a': 'Lieberman M, Peet A. Figure 11.2 Schematic view of a eukaryotic gene structure. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 255. Figure 14.4 A schematic view of a eukarytoic gene, and steps required to produce a protein product. 2017. Added Myoglobin by AzaToth. Public domain. From Wikimedia Commons.', '8d4cb77f-7f72-4b2a-be0c-d69ce210a1bc': '11.2 Protein Translation', '966dd498-fc0e-412c-9c85-196e7ce837b9': 'Translation is the process by which mRNAs are converted into protein products through the interactions of mRNA, tRNA, and rRNA. Even before an mRNA is translated, a cell must invest energy to build each of its ribosomes, a complex macromolecule composed of structural and catalytic rRNAs, and many distinct polypeptides. In eukaryotes, the nucleolus is completely specialized for the synthesis and assembly of rRNAs.', '3808c5de-4ff8-4647-8c5f-e05e084f6753': 'Ribosomes exist in the cytoplasm and rough endoplasmic reticulum of eukaryotes. Ribosomes dissociate into large and small subunits when they are not synthesizing proteins and reassociate during the initiation of translation.', '8b79b097-d0ac-4a62-b605-e236e472f0bc': 'Each mRNA molecule is simultaneously translated by many ribosomes, all synthesizing protein in the same direction: reading the mRNA from 5′ to 3′ and synthesizing the polypeptide from the N terminus to the C terminus. The complete mRNA/poly-ribosome structure is called a polysome.'}"
Figure 11.8,cell_bio/images/Figure 11.8.jpg,Figure 11.8: Summary of translational elongation.,"Translation is initiated by the assembly of the small ribosomal subunit (40S) with initiation factors (IF), which recognize the 5ʼ cap of the mRNA. This is referred to as the cap-binding complex, and this will scan the mRNA for the initial AUG needed to start translation. Once at the cap, the initiation complex tracks along the mRNA in the 5′ to 3′ direction, searching for the AUG start codon. Many eukaryotic mRNAs are translated from the first AUG, but this is not always the case. Once the appropriate AUG is identified, the other proteins and CBP dissociate, and the 60S subunit binds to the complex of Met-tRNAi, mRNA, and the 40S subunit. This step completes the initiation of translation in eukaryotes (figure 11.8).","{'37bdb907-a86b-4f97-ab65-584c9710c87a': 'In translation, the complex that assembles to start the process is referred to as the translation initiation complex, and similar to transcription, this complex can be activated or inhibited. In eukaryotes, translation is initiated by binding the initiating met-tRNAi to the 40S ribosome.', '926b42ec-c92b-44c7-97f6-44e2479f1895': 'Initially the met-tRNAi is brought to the 40S ribosome by a protein initiation factor, eukaryotic initiation factor-2 (eIF-2). The eIF-2 protein binds to the high-energy molecule guanosine triphosphate (GTP), and the tRNA-eIF2-GTP complex then binds to the 40S ribosome.', '770b9711-0232-40e8-ab64-40ee0d174bd2': 'The cap-binding protein eIF4F brings the mRNA complex together with the 40S ribosome complex. The ribosome then scans along the mRNA until it finds a start codon AUG. When the anticodon of the initiator tRNA and the start codon are aligned, the GTP is hydrolyzed, the initiation factors are released, and the large 60S ribosomal subunit binds to form the translation complex. Insulin increases the efficiency of formation of the cap-binding complex, therefore increasing the rate of protein synthesis.', '6688d9da-2c39-4d8d-be5d-63939d208064': 'The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly, and translation is impeded (figure 12.4).', '457442d7-5171-457c-9e5c-05c7bf133402': 'When eIF-2 remains unphosphorylated, the initiation complex can form normally, and translation can continue.', '2e4603d9-00fc-4d15-bf97-3255dbe2b61c': 'Translation is initiated by the assembly of the small ribosomal subunit (40S) with initiation factors (IF), which recognize the 5ʼ cap of the mRNA. This is referred to as the cap-binding complex, and this will scan the mRNA for the initial AUG needed to start translation. Once at the cap, the initiation complex tracks along the mRNA in the 5′ to 3′ direction, searching for the AUG start codon. Many eukaryotic mRNAs are translated from the first AUG, but this is not always the case. Once the appropriate AUG is identified, the other proteins and CBP dissociate, and the 60S subunit binds to the complex of Met-tRNAi, mRNA, and the 40S subunit. This step completes the initiation of translation in eukaryotes (figure 11.8).', '87489772-7067-4758-a8fe-316a9b7495c9': 'The ribosome has three\xa0locations for tRNA binding: A, P, and E sites.', '2df1ec5a-7e99-46a9-9b66-91b15ecd5d7f': 'Translation elongation requires energy in the form of GTP, and additional elongation factors (EFs) are required for this process. Elongation proceeds with charged tRNAs sequentially entering and leaving the ribosome as each new amino acid is added to the polypeptide chain. Movement of a tRNA from A to P to E sites is induced by conformational changes that advance the ribosome by three bases in the 3′ direction. GTP energy is required both for the binding of a new aminoacyl-tRNA to the A site and for its translocation to the P site after formation of the peptide bond.', '98418d94-72ff-4f75-b28b-368aa72cb3b9': 'Peptide bonds form between the amino group of the amino acid attached to the A-site tRNA and the carboxyl group of the amino acid attached to the P-site tRNA. A new tRNA with the corresponding amino acid coded for by the mRNA will enter into the A site of the ribosome.', '10e585d1-c464-4f24-8631-3004e2902b9b': 'The amino acid attached to the tRNA in the P site will be transferred to the tRNA in the A site; this is referred to as the peptidyl transferase react ion. The tRNAs will slide such that the tRNA in the P site will move to the E site and the tRNA in the A site will move to the P site. The tRNA in the E site will be released, and a new tRNA will enter into the A site, and the process will continue with the addition of tRNAs in the manner until the full message is transcribed (figure 11.8).', '1feb638e-77f1-4422-8c1b-0ab29c5c020b': 'Termination of translation occurs when a nonsense codon (UAA, UAG, or UGA) is encountered. Upon aligning with the A site, these nonsense codons are recognized by protein release factors that resemble tRNAs.', 'fb58528e-c6a3-4364-8d37-9990b16d3531': 'The release\xa0factors in both prokaryotes and eukaryotes instruct peptidyl transferase to add a water molecule to the carboxyl end of the P-site amino acid. This reaction forces the P-site amino acid to detach from its tRNA, and the newly made protein is released.', 'a03e10d4-1a16-471f-86b4-fd7ae851a0c3': 'The small and large ribosomal subunits dissociate from the mRNA and from each other; they are recruited almost immediately into another translation initiation complex. After many ribosomes have completed translation, the mRNA is degraded so the nucleotides can be reused in another transcription reaction.', '2b71cef6-e1c8-4083-b72b-3ed555b8bdb9': '11.2 References and resources'}"
Figure 11.8,cell_bio/images/Figure 11.8.jpg,Figure 11.8: Summary of translational elongation.,"Translation is initiated by the assembly of the small ribosomal subunit (40S) with initiation factors (IF), which recognize the 5ʼ cap of the mRNA. This is referred to as the cap-binding complex, and this will scan the mRNA for the initial AUG needed to start translation. Once at the cap, the initiation complex tracks along the mRNA in the 5′ to 3′ direction, searching for the AUG start codon. Many eukaryotic mRNAs are translated from the first AUG, but this is not always the case. Once the appropriate AUG is identified, the other proteins and CBP dissociate, and the 60S subunit binds to the complex of Met-tRNAi, mRNA, and the 40S subunit. This step completes the initiation of translation in eukaryotes (figure 11.8).","{'37bdb907-a86b-4f97-ab65-584c9710c87a': 'In translation, the complex that assembles to start the process is referred to as the translation initiation complex, and similar to transcription, this complex can be activated or inhibited. In eukaryotes, translation is initiated by binding the initiating met-tRNAi to the 40S ribosome.', '926b42ec-c92b-44c7-97f6-44e2479f1895': 'Initially the met-tRNAi is brought to the 40S ribosome by a protein initiation factor, eukaryotic initiation factor-2 (eIF-2). The eIF-2 protein binds to the high-energy molecule guanosine triphosphate (GTP), and the tRNA-eIF2-GTP complex then binds to the 40S ribosome.', '770b9711-0232-40e8-ab64-40ee0d174bd2': 'The cap-binding protein eIF4F brings the mRNA complex together with the 40S ribosome complex. The ribosome then scans along the mRNA until it finds a start codon AUG. When the anticodon of the initiator tRNA and the start codon are aligned, the GTP is hydrolyzed, the initiation factors are released, and the large 60S ribosomal subunit binds to form the translation complex. Insulin increases the efficiency of formation of the cap-binding complex, therefore increasing the rate of protein synthesis.', '6688d9da-2c39-4d8d-be5d-63939d208064': 'The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly, and translation is impeded (figure 12.4).', '457442d7-5171-457c-9e5c-05c7bf133402': 'When eIF-2 remains unphosphorylated, the initiation complex can form normally, and translation can continue.', '2e4603d9-00fc-4d15-bf97-3255dbe2b61c': 'Translation is initiated by the assembly of the small ribosomal subunit (40S) with initiation factors (IF), which recognize the 5ʼ cap of the mRNA. This is referred to as the cap-binding complex, and this will scan the mRNA for the initial AUG needed to start translation. Once at the cap, the initiation complex tracks along the mRNA in the 5′ to 3′ direction, searching for the AUG start codon. Many eukaryotic mRNAs are translated from the first AUG, but this is not always the case. Once the appropriate AUG is identified, the other proteins and CBP dissociate, and the 60S subunit binds to the complex of Met-tRNAi, mRNA, and the 40S subunit. This step completes the initiation of translation in eukaryotes (figure 11.8).', '87489772-7067-4758-a8fe-316a9b7495c9': 'The ribosome has three\xa0locations for tRNA binding: A, P, and E sites.', '2df1ec5a-7e99-46a9-9b66-91b15ecd5d7f': 'Translation elongation requires energy in the form of GTP, and additional elongation factors (EFs) are required for this process. Elongation proceeds with charged tRNAs sequentially entering and leaving the ribosome as each new amino acid is added to the polypeptide chain. Movement of a tRNA from A to P to E sites is induced by conformational changes that advance the ribosome by three bases in the 3′ direction. GTP energy is required both for the binding of a new aminoacyl-tRNA to the A site and for its translocation to the P site after formation of the peptide bond.', '98418d94-72ff-4f75-b28b-368aa72cb3b9': 'Peptide bonds form between the amino group of the amino acid attached to the A-site tRNA and the carboxyl group of the amino acid attached to the P-site tRNA. A new tRNA with the corresponding amino acid coded for by the mRNA will enter into the A site of the ribosome.', '10e585d1-c464-4f24-8631-3004e2902b9b': 'The amino acid attached to the tRNA in the P site will be transferred to the tRNA in the A site; this is referred to as the peptidyl transferase react ion. The tRNAs will slide such that the tRNA in the P site will move to the E site and the tRNA in the A site will move to the P site. The tRNA in the E site will be released, and a new tRNA will enter into the A site, and the process will continue with the addition of tRNAs in the manner until the full message is transcribed (figure 11.8).', '1feb638e-77f1-4422-8c1b-0ab29c5c020b': 'Termination of translation occurs when a nonsense codon (UAA, UAG, or UGA) is encountered. Upon aligning with the A site, these nonsense codons are recognized by protein release factors that resemble tRNAs.', 'fb58528e-c6a3-4364-8d37-9990b16d3531': 'The release\xa0factors in both prokaryotes and eukaryotes instruct peptidyl transferase to add a water molecule to the carboxyl end of the P-site amino acid. This reaction forces the P-site amino acid to detach from its tRNA, and the newly made protein is released.', 'a03e10d4-1a16-471f-86b4-fd7ae851a0c3': 'The small and large ribosomal subunits dissociate from the mRNA and from each other; they are recruited almost immediately into another translation initiation complex. After many ribosomes have completed translation, the mRNA is degraded so the nucleotides can be reused in another transcription reaction.', '2b71cef6-e1c8-4083-b72b-3ed555b8bdb9': '11.2 References and resources'}"
Figure 11.6,cell_bio/images/Figure 11.6.jpg,,"Figure 11.6: Genetic code; each codons is three nucleotides corresponding to a specific amino acid. The code is degenerate, meaning several codes are present for the same amino acid and the codes for similar amino acids are clustered.","{'1feb638e-77f1-4422-8c1b-0ab29c5c020b': 'Termination of translation occurs when a nonsense codon (UAA, UAG, or UGA) is encountered. Upon aligning with the A site, these nonsense codons are recognized by protein release factors that resemble tRNAs.', 'fb58528e-c6a3-4364-8d37-9990b16d3531': 'The release\xa0factors in both prokaryotes and eukaryotes instruct peptidyl transferase to add a water molecule to the carboxyl end of the P-site amino acid. This reaction forces the P-site amino acid to detach from its tRNA, and the newly made protein is released.', 'a03e10d4-1a16-471f-86b4-fd7ae851a0c3': 'The small and large ribosomal subunits dissociate from the mRNA and from each other; they are recruited almost immediately into another translation initiation complex. After many ribosomes have completed translation, the mRNA is degraded so the nucleotides can be reused in another transcription reaction.', '2b71cef6-e1c8-4083-b72b-3ed555b8bdb9': '11.2 References and resources'}"
Figure 11.7,cell_bio/images/Figure 11.7.jpg,,"Figure 11.7: Summary of translational initiation. eIF4 recruits the small ribosomal subunit and other initiation factors to the mRNA. The charge Met-tRNA also binds the complex, and the large ribosomal subunit is recruited to the initiation complex. Once the large ribosomal subunit binds, the initiation factors can be released, and translation can proceed to elongation of the polypeptide chain.","{'1feb638e-77f1-4422-8c1b-0ab29c5c020b': 'Termination of translation occurs when a nonsense codon (UAA, UAG, or UGA) is encountered. Upon aligning with the A site, these nonsense codons are recognized by protein release factors that resemble tRNAs.', 'fb58528e-c6a3-4364-8d37-9990b16d3531': 'The release\xa0factors in both prokaryotes and eukaryotes instruct peptidyl transferase to add a water molecule to the carboxyl end of the P-site amino acid. This reaction forces the P-site amino acid to detach from its tRNA, and the newly made protein is released.', 'a03e10d4-1a16-471f-86b4-fd7ae851a0c3': 'The small and large ribosomal subunits dissociate from the mRNA and from each other; they are recruited almost immediately into another translation initiation complex. After many ribosomes have completed translation, the mRNA is degraded so the nucleotides can be reused in another transcription reaction.', '2b71cef6-e1c8-4083-b72b-3ed555b8bdb9': '11.2 References and resources'}"
Figure 11.8,cell_bio/images/Figure 11.8.jpg,Figure 11.8: Summary of translational elongation.,"Translation is initiated by the assembly of the small ribosomal subunit (40S) with initiation factors (IF), which recognize the 5ʼ cap of the mRNA. This is referred to as the cap-binding complex, and this will scan the mRNA for the initial AUG needed to start translation. Once at the cap, the initiation complex tracks along the mRNA in the 5′ to 3′ direction, searching for the AUG start codon. Many eukaryotic mRNAs are translated from the first AUG, but this is not always the case. Once the appropriate AUG is identified, the other proteins and CBP dissociate, and the 60S subunit binds to the complex of Met-tRNAi, mRNA, and the 40S subunit. This step completes the initiation of translation in eukaryotes (figure 11.8).","{'37bdb907-a86b-4f97-ab65-584c9710c87a': 'In translation, the complex that assembles to start the process is referred to as the translation initiation complex, and similar to transcription, this complex can be activated or inhibited. In eukaryotes, translation is initiated by binding the initiating met-tRNAi to the 40S ribosome.', '926b42ec-c92b-44c7-97f6-44e2479f1895': 'Initially the met-tRNAi is brought to the 40S ribosome by a protein initiation factor, eukaryotic initiation factor-2 (eIF-2). The eIF-2 protein binds to the high-energy molecule guanosine triphosphate (GTP), and the tRNA-eIF2-GTP complex then binds to the 40S ribosome.', '770b9711-0232-40e8-ab64-40ee0d174bd2': 'The cap-binding protein eIF4F brings the mRNA complex together with the 40S ribosome complex. The ribosome then scans along the mRNA until it finds a start codon AUG. When the anticodon of the initiator tRNA and the start codon are aligned, the GTP is hydrolyzed, the initiation factors are released, and the large 60S ribosomal subunit binds to form the translation complex. Insulin increases the efficiency of formation of the cap-binding complex, therefore increasing the rate of protein synthesis.', '6688d9da-2c39-4d8d-be5d-63939d208064': 'The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly, and translation is impeded (figure 12.4).', '457442d7-5171-457c-9e5c-05c7bf133402': 'When eIF-2 remains unphosphorylated, the initiation complex can form normally, and translation can continue.', '2e4603d9-00fc-4d15-bf97-3255dbe2b61c': 'Translation is initiated by the assembly of the small ribosomal subunit (40S) with initiation factors (IF), which recognize the 5ʼ cap of the mRNA. This is referred to as the cap-binding complex, and this will scan the mRNA for the initial AUG needed to start translation. Once at the cap, the initiation complex tracks along the mRNA in the 5′ to 3′ direction, searching for the AUG start codon. Many eukaryotic mRNAs are translated from the first AUG, but this is not always the case. Once the appropriate AUG is identified, the other proteins and CBP dissociate, and the 60S subunit binds to the complex of Met-tRNAi, mRNA, and the 40S subunit. This step completes the initiation of translation in eukaryotes (figure 11.8).', '87489772-7067-4758-a8fe-316a9b7495c9': 'The ribosome has three\xa0locations for tRNA binding: A, P, and E sites.', '2df1ec5a-7e99-46a9-9b66-91b15ecd5d7f': 'Translation elongation requires energy in the form of GTP, and additional elongation factors (EFs) are required for this process. Elongation proceeds with charged tRNAs sequentially entering and leaving the ribosome as each new amino acid is added to the polypeptide chain. Movement of a tRNA from A to P to E sites is induced by conformational changes that advance the ribosome by three bases in the 3′ direction. GTP energy is required both for the binding of a new aminoacyl-tRNA to the A site and for its translocation to the P site after formation of the peptide bond.', '98418d94-72ff-4f75-b28b-368aa72cb3b9': 'Peptide bonds form between the amino group of the amino acid attached to the A-site tRNA and the carboxyl group of the amino acid attached to the P-site tRNA. A new tRNA with the corresponding amino acid coded for by the mRNA will enter into the A site of the ribosome.', '10e585d1-c464-4f24-8631-3004e2902b9b': 'The amino acid attached to the tRNA in the P site will be transferred to the tRNA in the A site; this is referred to as the peptidyl transferase react ion. The tRNAs will slide such that the tRNA in the P site will move to the E site and the tRNA in the A site will move to the P site. The tRNA in the E site will be released, and a new tRNA will enter into the A site, and the process will continue with the addition of tRNAs in the manner until the full message is transcribed (figure 11.8).', '1feb638e-77f1-4422-8c1b-0ab29c5c020b': 'Termination of translation occurs when a nonsense codon (UAA, UAG, or UGA) is encountered. Upon aligning with the A site, these nonsense codons are recognized by protein release factors that resemble tRNAs.', 'fb58528e-c6a3-4364-8d37-9990b16d3531': 'The release\xa0factors in both prokaryotes and eukaryotes instruct peptidyl transferase to add a water molecule to the carboxyl end of the P-site amino acid. This reaction forces the P-site amino acid to detach from its tRNA, and the newly made protein is released.', 'a03e10d4-1a16-471f-86b4-fd7ae851a0c3': 'The small and large ribosomal subunits dissociate from the mRNA and from each other; they are recruited almost immediately into another translation initiation complex. After many ribosomes have completed translation, the mRNA is degraded so the nucleotides can be reused in another transcription reaction.', '2b71cef6-e1c8-4083-b72b-3ed555b8bdb9': '11.2 References and resources'}"
Figure 10.3,cell_bio/images/Figure 10.3.jpg,Figure 10.3: General structure and hydrogen bonding pattern of DNA.,DNA has a double helix structure and phosphodiester bonds; the dotted lines between thymine and adenine and guanine and cytosine represent hydrogen bonds. The major and minor grooves are binding sites for DNA-binding proteins during processes such as transcription (the copying of RNA from DNA) and replication (figure 10.3).,"{'3f30ee6e-ffd0-40c8-9885-8e80cea49da2': 'The nucleotides combine with each other to produce phosphodiester bonds. The phosphate residue attached to the 5′ carbon of the sugar of one nucleotide forms a second ester linkage with the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, thereby forming a 5′-3′ phosphodiester bond. In a polynucleotide, one end of the chain has a free 5′ phosphate, and the other end has a free 3′-OH. These are called the 5′ and 3′ ends of the chain.', '0b055861-5c47-4297-8ad1-353a0950fefc': 'Base-pairing takes place between a purine and pyrimidine on opposite strands, so that adenine and thymine are complementary base pairs, and cytosine and guanine are also complementary base pairs. The base pairs are stabilized by hydrogen bonds: adenine and thymine form two hydrogen bonds, and cytosine and guanine form three hydrogen bonds. The two strands are anti-parallel in nature; that is, the 3′ end of one strand faces the 5′ end of the other strand. The sugar and phosphate of the nucleotides form the backbone of the structure, whereas the nitrogenous bases are stacked inside, like the rungs of a ladder. The twisting of the two strands around each other results in the formation of uniformly spaced major and minor grooves.', '405cb74b-2ed3-429a-9423-9437a8b52280': 'DNA has a double helix structure and phosphodiester bonds; the dotted lines between thymine and adenine and guanine and cytosine represent hydrogen bonds. The major and minor grooves are binding sites for DNA-binding proteins during processes such as transcription (the copying of RNA from DNA) and replication\xa0(figure 10.3).', '1bf2c3c1-b4e9-45d9-a41d-c56bacd8ccb4': 'Eukaryotic chromosomes consist of a linear DNA molecule\xa0complexed with protein (histones);\xa0this complex is called chromatin. Histones are evolutionarily conserved proteins that are rich in basic amino acids and form an octamer composed of two molecules of each of four different histones.', 'cde557b8-26ab-43e0-ab5b-935bcdd02d9a': 'The DNA (remember, it is negatively charged because of the phosphate groups) is wrapped tightly around the histone core. This interaction is facilitated through electrostatic interactions. The negatively charged phosphate groups on the DNA backbone are attracted to a positively charged lysine on the exposed surface of histones. This nucleosome is linked to the next one with the help of a linker DNA. This is also known as the “beads on a string” structure. With the help of a fifth histone, a string of nucleosomes is further compacted into a 30 nm fiber, which is the diameter of the structure. Metaphase chromosomes are even further condensed by association with scaffolding proteins. At the metaphase stage, the chromosomes are at their most compact, approximately 700 nm in width (figure 10.4).', '72738197-56e2-4a37-98c5-30962c2676ff': 'In interphase, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. The tightly packaged region is known as heterochromatin, and the less dense region is known as euchromatin.', '9171b2ea-08b5-4d27-aedb-64a9f91a5a9c': 'Heterochromatin usually contains genes that are not expressed\xa0and is found in the regions of the centromere and telomeres.', 'd63eea7e-edcb-4e55-ab24-a9a677064c4b': 'The euchromatin usually contains genes that are transcribed, with DNA packaged around nucleosomes but not further compacted.', '2c4513a4-2a86-4cf9-8931-6cdeb52dbedd': 'Histone tails can be modified through both methylation and acetylation, which will alter the histone:DNA interaction. Histone methylation can have variable impacts on a given gene locus leading to a change in transcription. Histone acetylation relaxes the interactions of histones and DNA by removing the positive charge on lysine residues allowing the DNA to be transcriptionally accessible (euchromatin). DNA methylation, specifically to CpG islands, globally represses transcription. These modifications on histones and DNA\xa0can result in epigenetic influences that have an impact on many biological processes.', '032ca653-9837-4376-bb42-169f4567c217': 'Across the three\xa0billion base pair genome, genes are organized into clusters with only a fraction of the DNA coding for translated products. The remaining DNA was historically considered “junk,”\xa0however, more recently there is a new appreciation for the roles of noncoding DNA regions. Only half of the genome is unique DNA sequence, and only 1.5 percent\xa0codes for mRNA (~20,000 protein-coding genes). The remaining sequence can be categorized as:', '85d55426-c44f-426c-9ed9-bac98d6dd169': '10.1 References and resources', 'e94b1cab-3161-4850-9e0c-731242929910': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 14: DNA Structure and Function.', '32a0fa07-bed4-42f6-94c2-6184c6996692': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 10: The Nature of the Gene and the Genome, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication.', 'c88b2c4c-3b5e-4b38-8c5a-67684644b5b9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 34, 38–40.', '5cd1ab88-84e4-441e-be49-47194df0ea17': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 2: The Introduction to the Human Genome.', '720ababc-cfc4-41b0-8650-0e79cccf3fcf': '10.2 DNA Repair', '3b87f707-c0e5-42f9-94bf-1fd8a4ebebab': 'DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase (DNA pol) inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.', '77129dfc-e395-4ef2-ae0b-848536a15460': 'Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).'}"
Figure 10.4,cell_bio/images/Figure 10.4.jpg,Figure 10.4: Organizational structure of DNA illustrating condensation and supercoiling into chromosomes.,"The DNA (remember, it is negatively charged because of the phosphate groups) is wrapped tightly around the histone core. This interaction is facilitated through electrostatic interactions. The negatively charged phosphate groups on the DNA backbone are attracted to a positively charged lysine on the exposed surface of histones. This nucleosome is linked to the next one with the help of a linker DNA. This is also known as the “beads on a string” structure. With the help of a fifth histone, a string of nucleosomes is further compacted into a 30 nm fiber, which is the diameter of the structure. Metaphase chromosomes are even further condensed by association with scaffolding proteins. At the metaphase stage, the chromosomes are at their most compact, approximately 700 nm in width (figure 10.4).","{'1bf2c3c1-b4e9-45d9-a41d-c56bacd8ccb4': 'Eukaryotic chromosomes consist of a linear DNA molecule\xa0complexed with protein (histones);\xa0this complex is called chromatin. Histones are evolutionarily conserved proteins that are rich in basic amino acids and form an octamer composed of two molecules of each of four different histones.', 'cde557b8-26ab-43e0-ab5b-935bcdd02d9a': 'The DNA (remember, it is negatively charged because of the phosphate groups) is wrapped tightly around the histone core. This interaction is facilitated through electrostatic interactions. The negatively charged phosphate groups on the DNA backbone are attracted to a positively charged lysine on the exposed surface of histones. This nucleosome is linked to the next one with the help of a linker DNA. This is also known as the “beads on a string” structure. With the help of a fifth histone, a string of nucleosomes is further compacted into a 30 nm fiber, which is the diameter of the structure. Metaphase chromosomes are even further condensed by association with scaffolding proteins. At the metaphase stage, the chromosomes are at their most compact, approximately 700 nm in width (figure 10.4).', '72738197-56e2-4a37-98c5-30962c2676ff': 'In interphase, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. The tightly packaged region is known as heterochromatin, and the less dense region is known as euchromatin.', '9171b2ea-08b5-4d27-aedb-64a9f91a5a9c': 'Heterochromatin usually contains genes that are not expressed\xa0and is found in the regions of the centromere and telomeres.', 'd63eea7e-edcb-4e55-ab24-a9a677064c4b': 'The euchromatin usually contains genes that are transcribed, with DNA packaged around nucleosomes but not further compacted.', '2c4513a4-2a86-4cf9-8931-6cdeb52dbedd': 'Histone tails can be modified through both methylation and acetylation, which will alter the histone:DNA interaction. Histone methylation can have variable impacts on a given gene locus leading to a change in transcription. Histone acetylation relaxes the interactions of histones and DNA by removing the positive charge on lysine residues allowing the DNA to be transcriptionally accessible (euchromatin). DNA methylation, specifically to CpG islands, globally represses transcription. These modifications on histones and DNA\xa0can result in epigenetic influences that have an impact on many biological processes.', '032ca653-9837-4376-bb42-169f4567c217': 'Across the three\xa0billion base pair genome, genes are organized into clusters with only a fraction of the DNA coding for translated products. The remaining DNA was historically considered “junk,”\xa0however, more recently there is a new appreciation for the roles of noncoding DNA regions. Only half of the genome is unique DNA sequence, and only 1.5 percent\xa0codes for mRNA (~20,000 protein-coding genes). The remaining sequence can be categorized as:', '85d55426-c44f-426c-9ed9-bac98d6dd169': '10.1 References and resources', 'e94b1cab-3161-4850-9e0c-731242929910': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 14: DNA Structure and Function.', '32a0fa07-bed4-42f6-94c2-6184c6996692': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 10: The Nature of the Gene and the Genome, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication.', 'c88b2c4c-3b5e-4b38-8c5a-67684644b5b9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 34, 38–40.', '5cd1ab88-84e4-441e-be49-47194df0ea17': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 2: The Introduction to the Human Genome.', '720ababc-cfc4-41b0-8650-0e79cccf3fcf': '10.2 DNA Repair', '3b87f707-c0e5-42f9-94bf-1fd8a4ebebab': 'DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase (DNA pol) inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.', '77129dfc-e395-4ef2-ae0b-848536a15460': 'Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).'}"
Figure 10.1,cell_bio/images/Figure 10.1.jpg,,"Figure 10.1: Basic structure of nucleotides including the sugar (ribose or deoxyribose), base (pyrimidine or purine), and phosphate groups.","{'1bf2c3c1-b4e9-45d9-a41d-c56bacd8ccb4': 'Eukaryotic chromosomes consist of a linear DNA molecule\xa0complexed with protein (histones);\xa0this complex is called chromatin. Histones are evolutionarily conserved proteins that are rich in basic amino acids and form an octamer composed of two molecules of each of four different histones.', 'cde557b8-26ab-43e0-ab5b-935bcdd02d9a': 'The DNA (remember, it is negatively charged because of the phosphate groups) is wrapped tightly around the histone core. This interaction is facilitated through electrostatic interactions. The negatively charged phosphate groups on the DNA backbone are attracted to a positively charged lysine on the exposed surface of histones. This nucleosome is linked to the next one with the help of a linker DNA. This is also known as the “beads on a string” structure. With the help of a fifth histone, a string of nucleosomes is further compacted into a 30 nm fiber, which is the diameter of the structure. Metaphase chromosomes are even further condensed by association with scaffolding proteins. At the metaphase stage, the chromosomes are at their most compact, approximately 700 nm in width (figure 10.4).', '72738197-56e2-4a37-98c5-30962c2676ff': 'In interphase, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. The tightly packaged region is known as heterochromatin, and the less dense region is known as euchromatin.', '9171b2ea-08b5-4d27-aedb-64a9f91a5a9c': 'Heterochromatin usually contains genes that are not expressed\xa0and is found in the regions of the centromere and telomeres.', 'd63eea7e-edcb-4e55-ab24-a9a677064c4b': 'The euchromatin usually contains genes that are transcribed, with DNA packaged around nucleosomes but not further compacted.', '2c4513a4-2a86-4cf9-8931-6cdeb52dbedd': 'Histone tails can be modified through both methylation and acetylation, which will alter the histone:DNA interaction. Histone methylation can have variable impacts on a given gene locus leading to a change in transcription. Histone acetylation relaxes the interactions of histones and DNA by removing the positive charge on lysine residues allowing the DNA to be transcriptionally accessible (euchromatin). DNA methylation, specifically to CpG islands, globally represses transcription. These modifications on histones and DNA\xa0can result in epigenetic influences that have an impact on many biological processes.', '032ca653-9837-4376-bb42-169f4567c217': 'Across the three\xa0billion base pair genome, genes are organized into clusters with only a fraction of the DNA coding for translated products. The remaining DNA was historically considered “junk,”\xa0however, more recently there is a new appreciation for the roles of noncoding DNA regions. Only half of the genome is unique DNA sequence, and only 1.5 percent\xa0codes for mRNA (~20,000 protein-coding genes). The remaining sequence can be categorized as:', '85d55426-c44f-426c-9ed9-bac98d6dd169': '10.1 References and resources', 'e94b1cab-3161-4850-9e0c-731242929910': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 14: DNA Structure and Function.', '32a0fa07-bed4-42f6-94c2-6184c6996692': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 10: The Nature of the Gene and the Genome, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication.', 'c88b2c4c-3b5e-4b38-8c5a-67684644b5b9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 34, 38–40.', '5cd1ab88-84e4-441e-be49-47194df0ea17': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 2: The Introduction to the Human Genome.', '720ababc-cfc4-41b0-8650-0e79cccf3fcf': '10.2 DNA Repair', '3b87f707-c0e5-42f9-94bf-1fd8a4ebebab': 'DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase (DNA pol) inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.', '77129dfc-e395-4ef2-ae0b-848536a15460': 'Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).'}"
Figure 10.2,cell_bio/images/Figure 10.2.jpg,,Figure 10.2: Structure of pyrimidine and purine bases.,"{'1bf2c3c1-b4e9-45d9-a41d-c56bacd8ccb4': 'Eukaryotic chromosomes consist of a linear DNA molecule\xa0complexed with protein (histones);\xa0this complex is called chromatin. Histones are evolutionarily conserved proteins that are rich in basic amino acids and form an octamer composed of two molecules of each of four different histones.', 'cde557b8-26ab-43e0-ab5b-935bcdd02d9a': 'The DNA (remember, it is negatively charged because of the phosphate groups) is wrapped tightly around the histone core. This interaction is facilitated through electrostatic interactions. The negatively charged phosphate groups on the DNA backbone are attracted to a positively charged lysine on the exposed surface of histones. This nucleosome is linked to the next one with the help of a linker DNA. This is also known as the “beads on a string” structure. With the help of a fifth histone, a string of nucleosomes is further compacted into a 30 nm fiber, which is the diameter of the structure. Metaphase chromosomes are even further condensed by association with scaffolding proteins. At the metaphase stage, the chromosomes are at their most compact, approximately 700 nm in width (figure 10.4).', '72738197-56e2-4a37-98c5-30962c2676ff': 'In interphase, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. The tightly packaged region is known as heterochromatin, and the less dense region is known as euchromatin.', '9171b2ea-08b5-4d27-aedb-64a9f91a5a9c': 'Heterochromatin usually contains genes that are not expressed\xa0and is found in the regions of the centromere and telomeres.', 'd63eea7e-edcb-4e55-ab24-a9a677064c4b': 'The euchromatin usually contains genes that are transcribed, with DNA packaged around nucleosomes but not further compacted.', '2c4513a4-2a86-4cf9-8931-6cdeb52dbedd': 'Histone tails can be modified through both methylation and acetylation, which will alter the histone:DNA interaction. Histone methylation can have variable impacts on a given gene locus leading to a change in transcription. Histone acetylation relaxes the interactions of histones and DNA by removing the positive charge on lysine residues allowing the DNA to be transcriptionally accessible (euchromatin). DNA methylation, specifically to CpG islands, globally represses transcription. These modifications on histones and DNA\xa0can result in epigenetic influences that have an impact on many biological processes.', '032ca653-9837-4376-bb42-169f4567c217': 'Across the three\xa0billion base pair genome, genes are organized into clusters with only a fraction of the DNA coding for translated products. The remaining DNA was historically considered “junk,”\xa0however, more recently there is a new appreciation for the roles of noncoding DNA regions. Only half of the genome is unique DNA sequence, and only 1.5 percent\xa0codes for mRNA (~20,000 protein-coding genes). The remaining sequence can be categorized as:', '85d55426-c44f-426c-9ed9-bac98d6dd169': '10.1 References and resources', 'e94b1cab-3161-4850-9e0c-731242929910': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 14: DNA Structure and Function.', '32a0fa07-bed4-42f6-94c2-6184c6996692': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 10: The Nature of the Gene and the Genome, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication.', 'c88b2c4c-3b5e-4b38-8c5a-67684644b5b9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 34, 38–40.', '5cd1ab88-84e4-441e-be49-47194df0ea17': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 2: The Introduction to the Human Genome.', '720ababc-cfc4-41b0-8650-0e79cccf3fcf': '10.2 DNA Repair', '3b87f707-c0e5-42f9-94bf-1fd8a4ebebab': 'DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase (DNA pol) inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.', '77129dfc-e395-4ef2-ae0b-848536a15460': 'Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).'}"
Figure 10.3,cell_bio/images/Figure 10.3.jpg,Figure 10.3: General structure and hydrogen bonding pattern of DNA.,DNA has a double helix structure and phosphodiester bonds; the dotted lines between thymine and adenine and guanine and cytosine represent hydrogen bonds. The major and minor grooves are binding sites for DNA-binding proteins during processes such as transcription (the copying of RNA from DNA) and replication (figure 10.3).,"{'3f30ee6e-ffd0-40c8-9885-8e80cea49da2': 'The nucleotides combine with each other to produce phosphodiester bonds. The phosphate residue attached to the 5′ carbon of the sugar of one nucleotide forms a second ester linkage with the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, thereby forming a 5′-3′ phosphodiester bond. In a polynucleotide, one end of the chain has a free 5′ phosphate, and the other end has a free 3′-OH. These are called the 5′ and 3′ ends of the chain.', '0b055861-5c47-4297-8ad1-353a0950fefc': 'Base-pairing takes place between a purine and pyrimidine on opposite strands, so that adenine and thymine are complementary base pairs, and cytosine and guanine are also complementary base pairs. The base pairs are stabilized by hydrogen bonds: adenine and thymine form two hydrogen bonds, and cytosine and guanine form three hydrogen bonds. The two strands are anti-parallel in nature; that is, the 3′ end of one strand faces the 5′ end of the other strand. The sugar and phosphate of the nucleotides form the backbone of the structure, whereas the nitrogenous bases are stacked inside, like the rungs of a ladder. The twisting of the two strands around each other results in the formation of uniformly spaced major and minor grooves.', '405cb74b-2ed3-429a-9423-9437a8b52280': 'DNA has a double helix structure and phosphodiester bonds; the dotted lines between thymine and adenine and guanine and cytosine represent hydrogen bonds. The major and minor grooves are binding sites for DNA-binding proteins during processes such as transcription (the copying of RNA from DNA) and replication\xa0(figure 10.3).', '1bf2c3c1-b4e9-45d9-a41d-c56bacd8ccb4': 'Eukaryotic chromosomes consist of a linear DNA molecule\xa0complexed with protein (histones);\xa0this complex is called chromatin. Histones are evolutionarily conserved proteins that are rich in basic amino acids and form an octamer composed of two molecules of each of four different histones.', 'cde557b8-26ab-43e0-ab5b-935bcdd02d9a': 'The DNA (remember, it is negatively charged because of the phosphate groups) is wrapped tightly around the histone core. This interaction is facilitated through electrostatic interactions. The negatively charged phosphate groups on the DNA backbone are attracted to a positively charged lysine on the exposed surface of histones. This nucleosome is linked to the next one with the help of a linker DNA. This is also known as the “beads on a string” structure. With the help of a fifth histone, a string of nucleosomes is further compacted into a 30 nm fiber, which is the diameter of the structure. Metaphase chromosomes are even further condensed by association with scaffolding proteins. At the metaphase stage, the chromosomes are at their most compact, approximately 700 nm in width (figure 10.4).', '72738197-56e2-4a37-98c5-30962c2676ff': 'In interphase, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. The tightly packaged region is known as heterochromatin, and the less dense region is known as euchromatin.', '9171b2ea-08b5-4d27-aedb-64a9f91a5a9c': 'Heterochromatin usually contains genes that are not expressed\xa0and is found in the regions of the centromere and telomeres.', 'd63eea7e-edcb-4e55-ab24-a9a677064c4b': 'The euchromatin usually contains genes that are transcribed, with DNA packaged around nucleosomes but not further compacted.', '2c4513a4-2a86-4cf9-8931-6cdeb52dbedd': 'Histone tails can be modified through both methylation and acetylation, which will alter the histone:DNA interaction. Histone methylation can have variable impacts on a given gene locus leading to a change in transcription. Histone acetylation relaxes the interactions of histones and DNA by removing the positive charge on lysine residues allowing the DNA to be transcriptionally accessible (euchromatin). DNA methylation, specifically to CpG islands, globally represses transcription. These modifications on histones and DNA\xa0can result in epigenetic influences that have an impact on many biological processes.', '032ca653-9837-4376-bb42-169f4567c217': 'Across the three\xa0billion base pair genome, genes are organized into clusters with only a fraction of the DNA coding for translated products. The remaining DNA was historically considered “junk,”\xa0however, more recently there is a new appreciation for the roles of noncoding DNA regions. Only half of the genome is unique DNA sequence, and only 1.5 percent\xa0codes for mRNA (~20,000 protein-coding genes). The remaining sequence can be categorized as:', '85d55426-c44f-426c-9ed9-bac98d6dd169': '10.1 References and resources', 'e94b1cab-3161-4850-9e0c-731242929910': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 14: DNA Structure and Function.', '32a0fa07-bed4-42f6-94c2-6184c6996692': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 10: The Nature of the Gene and the Genome, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication.', 'c88b2c4c-3b5e-4b38-8c5a-67684644b5b9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 34, 38–40.', '5cd1ab88-84e4-441e-be49-47194df0ea17': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 2: The Introduction to the Human Genome.', '720ababc-cfc4-41b0-8650-0e79cccf3fcf': '10.2 DNA Repair', '3b87f707-c0e5-42f9-94bf-1fd8a4ebebab': 'DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase (DNA pol) inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.', '77129dfc-e395-4ef2-ae0b-848536a15460': 'Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).'}"
Figure 10.5,cell_bio/images/Figure 10.5.jpg,"Figure 10.5: Comparison on three types of repair: (A) proofreading, (B) mismatch, and (C) nucleotide excision repair.","Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).","{'1bf2c3c1-b4e9-45d9-a41d-c56bacd8ccb4': 'Eukaryotic chromosomes consist of a linear DNA molecule\xa0complexed with protein (histones);\xa0this complex is called chromatin. Histones are evolutionarily conserved proteins that are rich in basic amino acids and form an octamer composed of two molecules of each of four different histones.', 'cde557b8-26ab-43e0-ab5b-935bcdd02d9a': 'The DNA (remember, it is negatively charged because of the phosphate groups) is wrapped tightly around the histone core. This interaction is facilitated through electrostatic interactions. The negatively charged phosphate groups on the DNA backbone are attracted to a positively charged lysine on the exposed surface of histones. This nucleosome is linked to the next one with the help of a linker DNA. This is also known as the “beads on a string” structure. With the help of a fifth histone, a string of nucleosomes is further compacted into a 30 nm fiber, which is the diameter of the structure. Metaphase chromosomes are even further condensed by association with scaffolding proteins. At the metaphase stage, the chromosomes are at their most compact, approximately 700 nm in width (figure 10.4).', '72738197-56e2-4a37-98c5-30962c2676ff': 'In interphase, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. The tightly packaged region is known as heterochromatin, and the less dense region is known as euchromatin.', '9171b2ea-08b5-4d27-aedb-64a9f91a5a9c': 'Heterochromatin usually contains genes that are not expressed\xa0and is found in the regions of the centromere and telomeres.', 'd63eea7e-edcb-4e55-ab24-a9a677064c4b': 'The euchromatin usually contains genes that are transcribed, with DNA packaged around nucleosomes but not further compacted.', '2c4513a4-2a86-4cf9-8931-6cdeb52dbedd': 'Histone tails can be modified through both methylation and acetylation, which will alter the histone:DNA interaction. Histone methylation can have variable impacts on a given gene locus leading to a change in transcription. Histone acetylation relaxes the interactions of histones and DNA by removing the positive charge on lysine residues allowing the DNA to be transcriptionally accessible (euchromatin). DNA methylation, specifically to CpG islands, globally represses transcription. These modifications on histones and DNA\xa0can result in epigenetic influences that have an impact on many biological processes.', '032ca653-9837-4376-bb42-169f4567c217': 'Across the three\xa0billion base pair genome, genes are organized into clusters with only a fraction of the DNA coding for translated products. The remaining DNA was historically considered “junk,”\xa0however, more recently there is a new appreciation for the roles of noncoding DNA regions. Only half of the genome is unique DNA sequence, and only 1.5 percent\xa0codes for mRNA (~20,000 protein-coding genes). The remaining sequence can be categorized as:', '85d55426-c44f-426c-9ed9-bac98d6dd169': '10.1 References and resources', 'e94b1cab-3161-4850-9e0c-731242929910': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 14: DNA Structure and Function.', '32a0fa07-bed4-42f6-94c2-6184c6996692': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 10: The Nature of the Gene and the Genome, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication.', 'c88b2c4c-3b5e-4b38-8c5a-67684644b5b9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 34, 38–40.', '5cd1ab88-84e4-441e-be49-47194df0ea17': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 2: The Introduction to the Human Genome.', '720ababc-cfc4-41b0-8650-0e79cccf3fcf': '10.2 DNA Repair', '3b87f707-c0e5-42f9-94bf-1fd8a4ebebab': 'DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase (DNA pol) inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.', '77129dfc-e395-4ef2-ae0b-848536a15460': 'Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).', '054d60a2-fbc6-409b-a40f-109f3eeff57a': 'Errors not addressed during replication are repaired through the process of mismatch repair (figure 10.5(b)). Specific repair enzymes recognize the mispaired nucleotide and excise part of the strand that contains it; the excised region is then resynthesized —\xa0typically during S phase of the cell cycle — and the enzymes involved are those used for DNA replication. If the mismatch remains uncorrected, it may lead to more permanent damage when the mismatched DNA is replicated. Deficiencies in this repair process can result in Lynch syndrome, which is characteristic of nonpolyposis colorectal cancer.', '4c748d6b-84ff-48d7-9b25-6ff0511c51c1': 'Another type of repair mechanism, nucleotide excision repair, is similar to mismatch repair, except that it is used to remove large, bulky damaged bases rather than mismatched ones. The repair enzymes replace abnormal, bulky, bases by making a cut on both the 3′ and 5′ ends of the damaged base. The segment of DNA is removed and replaced with the correctly paired nucleotides by the action of DNA pol. Once the bases are filled in, the remaining gap is sealed with a phosphodiester linkage catalyzed by DNA ligase (figure 10.5(c)).', 'a52185d6-3939-40ad-9a8c-947eaea82106': 'This repair mechanism is often employed when UV exposure causes the formation of pyrimidine dimers (thymine dimers). When exposed to UV light, thymines lying next to each other can form thymine dimers. In normal cells, they are excised and replaced. Xeroderma pigmentosa is a condition in which thymine dimerization from exposure to UV light is not repaired.', 'bb12ea63-1240-4890-87c8-d3a3278c3926': 'Double-stranded breaks are caused by ionizing radiation, such as X-rays or radioactive particles. This can be repaired through two processes: nonhomologous end-joining and homologous recombination. The major difference between these two processes is in nonhomologous end-joining there is direct ligation of the two ends without the need for a DNA template. This can result in some DNA being lost in the process. In contrast, homologous recombination requires a DNA template to repair the break. This allows for restoration of the duplex without a loss of nucleotides.', 'acf27e34-f0e2-4f70-8d3b-be20a9e5b6c0': '10.2 References and resources', '4a9b3ed2-d06c-49ce-9ff5-0368c2ceeae9': '10.3 DNA Replication'}"
Figure 10.5,cell_bio/images/Figure 10.5.jpg,"Figure 10.5: Comparison on three types of repair: (A) proofreading, (B) mismatch, and (C) nucleotide excision repair.","Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).","{'1bf2c3c1-b4e9-45d9-a41d-c56bacd8ccb4': 'Eukaryotic chromosomes consist of a linear DNA molecule\xa0complexed with protein (histones);\xa0this complex is called chromatin. Histones are evolutionarily conserved proteins that are rich in basic amino acids and form an octamer composed of two molecules of each of four different histones.', 'cde557b8-26ab-43e0-ab5b-935bcdd02d9a': 'The DNA (remember, it is negatively charged because of the phosphate groups) is wrapped tightly around the histone core. This interaction is facilitated through electrostatic interactions. The negatively charged phosphate groups on the DNA backbone are attracted to a positively charged lysine on the exposed surface of histones. This nucleosome is linked to the next one with the help of a linker DNA. This is also known as the “beads on a string” structure. With the help of a fifth histone, a string of nucleosomes is further compacted into a 30 nm fiber, which is the diameter of the structure. Metaphase chromosomes are even further condensed by association with scaffolding proteins. At the metaphase stage, the chromosomes are at their most compact, approximately 700 nm in width (figure 10.4).', '72738197-56e2-4a37-98c5-30962c2676ff': 'In interphase, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. The tightly packaged region is known as heterochromatin, and the less dense region is known as euchromatin.', '9171b2ea-08b5-4d27-aedb-64a9f91a5a9c': 'Heterochromatin usually contains genes that are not expressed\xa0and is found in the regions of the centromere and telomeres.', 'd63eea7e-edcb-4e55-ab24-a9a677064c4b': 'The euchromatin usually contains genes that are transcribed, with DNA packaged around nucleosomes but not further compacted.', '2c4513a4-2a86-4cf9-8931-6cdeb52dbedd': 'Histone tails can be modified through both methylation and acetylation, which will alter the histone:DNA interaction. Histone methylation can have variable impacts on a given gene locus leading to a change in transcription. Histone acetylation relaxes the interactions of histones and DNA by removing the positive charge on lysine residues allowing the DNA to be transcriptionally accessible (euchromatin). DNA methylation, specifically to CpG islands, globally represses transcription. These modifications on histones and DNA\xa0can result in epigenetic influences that have an impact on many biological processes.', '032ca653-9837-4376-bb42-169f4567c217': 'Across the three\xa0billion base pair genome, genes are organized into clusters with only a fraction of the DNA coding for translated products. The remaining DNA was historically considered “junk,”\xa0however, more recently there is a new appreciation for the roles of noncoding DNA regions. Only half of the genome is unique DNA sequence, and only 1.5 percent\xa0codes for mRNA (~20,000 protein-coding genes). The remaining sequence can be categorized as:', '85d55426-c44f-426c-9ed9-bac98d6dd169': '10.1 References and resources', 'e94b1cab-3161-4850-9e0c-731242929910': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 14: DNA Structure and Function.', '32a0fa07-bed4-42f6-94c2-6184c6996692': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 10: The Nature of the Gene and the Genome, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication.', 'c88b2c4c-3b5e-4b38-8c5a-67684644b5b9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 34, 38–40.', '5cd1ab88-84e4-441e-be49-47194df0ea17': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 2: The Introduction to the Human Genome.', '720ababc-cfc4-41b0-8650-0e79cccf3fcf': '10.2 DNA Repair', '3b87f707-c0e5-42f9-94bf-1fd8a4ebebab': 'DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase (DNA pol) inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.', '77129dfc-e395-4ef2-ae0b-848536a15460': 'Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).', '054d60a2-fbc6-409b-a40f-109f3eeff57a': 'Errors not addressed during replication are repaired through the process of mismatch repair (figure 10.5(b)). Specific repair enzymes recognize the mispaired nucleotide and excise part of the strand that contains it; the excised region is then resynthesized —\xa0typically during S phase of the cell cycle — and the enzymes involved are those used for DNA replication. If the mismatch remains uncorrected, it may lead to more permanent damage when the mismatched DNA is replicated. Deficiencies in this repair process can result in Lynch syndrome, which is characteristic of nonpolyposis colorectal cancer.', '4c748d6b-84ff-48d7-9b25-6ff0511c51c1': 'Another type of repair mechanism, nucleotide excision repair, is similar to mismatch repair, except that it is used to remove large, bulky damaged bases rather than mismatched ones. The repair enzymes replace abnormal, bulky, bases by making a cut on both the 3′ and 5′ ends of the damaged base. The segment of DNA is removed and replaced with the correctly paired nucleotides by the action of DNA pol. Once the bases are filled in, the remaining gap is sealed with a phosphodiester linkage catalyzed by DNA ligase (figure 10.5(c)).', 'a52185d6-3939-40ad-9a8c-947eaea82106': 'This repair mechanism is often employed when UV exposure causes the formation of pyrimidine dimers (thymine dimers). When exposed to UV light, thymines lying next to each other can form thymine dimers. In normal cells, they are excised and replaced. Xeroderma pigmentosa is a condition in which thymine dimerization from exposure to UV light is not repaired.', 'bb12ea63-1240-4890-87c8-d3a3278c3926': 'Double-stranded breaks are caused by ionizing radiation, such as X-rays or radioactive particles. This can be repaired through two processes: nonhomologous end-joining and homologous recombination. The major difference between these two processes is in nonhomologous end-joining there is direct ligation of the two ends without the need for a DNA template. This can result in some DNA being lost in the process. In contrast, homologous recombination requires a DNA template to repair the break. This allows for restoration of the duplex without a loss of nucleotides.', 'acf27e34-f0e2-4f70-8d3b-be20a9e5b6c0': '10.2 References and resources', '4a9b3ed2-d06c-49ce-9ff5-0368c2ceeae9': '10.3 DNA Replication'}"
Figure 10.5,cell_bio/images/Figure 10.5.jpg,"Figure 10.5: Comparison on three types of repair: (A) proofreading, (B) mismatch, and (C) nucleotide excision repair.","Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).","{'1bf2c3c1-b4e9-45d9-a41d-c56bacd8ccb4': 'Eukaryotic chromosomes consist of a linear DNA molecule\xa0complexed with protein (histones);\xa0this complex is called chromatin. Histones are evolutionarily conserved proteins that are rich in basic amino acids and form an octamer composed of two molecules of each of four different histones.', 'cde557b8-26ab-43e0-ab5b-935bcdd02d9a': 'The DNA (remember, it is negatively charged because of the phosphate groups) is wrapped tightly around the histone core. This interaction is facilitated through electrostatic interactions. The negatively charged phosphate groups on the DNA backbone are attracted to a positively charged lysine on the exposed surface of histones. This nucleosome is linked to the next one with the help of a linker DNA. This is also known as the “beads on a string” structure. With the help of a fifth histone, a string of nucleosomes is further compacted into a 30 nm fiber, which is the diameter of the structure. Metaphase chromosomes are even further condensed by association with scaffolding proteins. At the metaphase stage, the chromosomes are at their most compact, approximately 700 nm in width (figure 10.4).', '72738197-56e2-4a37-98c5-30962c2676ff': 'In interphase, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. The tightly packaged region is known as heterochromatin, and the less dense region is known as euchromatin.', '9171b2ea-08b5-4d27-aedb-64a9f91a5a9c': 'Heterochromatin usually contains genes that are not expressed\xa0and is found in the regions of the centromere and telomeres.', 'd63eea7e-edcb-4e55-ab24-a9a677064c4b': 'The euchromatin usually contains genes that are transcribed, with DNA packaged around nucleosomes but not further compacted.', '2c4513a4-2a86-4cf9-8931-6cdeb52dbedd': 'Histone tails can be modified through both methylation and acetylation, which will alter the histone:DNA interaction. Histone methylation can have variable impacts on a given gene locus leading to a change in transcription. Histone acetylation relaxes the interactions of histones and DNA by removing the positive charge on lysine residues allowing the DNA to be transcriptionally accessible (euchromatin). DNA methylation, specifically to CpG islands, globally represses transcription. These modifications on histones and DNA\xa0can result in epigenetic influences that have an impact on many biological processes.', '032ca653-9837-4376-bb42-169f4567c217': 'Across the three\xa0billion base pair genome, genes are organized into clusters with only a fraction of the DNA coding for translated products. The remaining DNA was historically considered “junk,”\xa0however, more recently there is a new appreciation for the roles of noncoding DNA regions. Only half of the genome is unique DNA sequence, and only 1.5 percent\xa0codes for mRNA (~20,000 protein-coding genes). The remaining sequence can be categorized as:', '85d55426-c44f-426c-9ed9-bac98d6dd169': '10.1 References and resources', 'e94b1cab-3161-4850-9e0c-731242929910': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 14: DNA Structure and Function.', '32a0fa07-bed4-42f6-94c2-6184c6996692': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 10: The Nature of the Gene and the Genome, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication.', 'c88b2c4c-3b5e-4b38-8c5a-67684644b5b9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 34, 38–40.', '5cd1ab88-84e4-441e-be49-47194df0ea17': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 2: The Introduction to the Human Genome.', '720ababc-cfc4-41b0-8650-0e79cccf3fcf': '10.2 DNA Repair', '3b87f707-c0e5-42f9-94bf-1fd8a4ebebab': 'DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase (DNA pol) inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.', '77129dfc-e395-4ef2-ae0b-848536a15460': 'Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).', '054d60a2-fbc6-409b-a40f-109f3eeff57a': 'Errors not addressed during replication are repaired through the process of mismatch repair (figure 10.5(b)). Specific repair enzymes recognize the mispaired nucleotide and excise part of the strand that contains it; the excised region is then resynthesized —\xa0typically during S phase of the cell cycle — and the enzymes involved are those used for DNA replication. If the mismatch remains uncorrected, it may lead to more permanent damage when the mismatched DNA is replicated. Deficiencies in this repair process can result in Lynch syndrome, which is characteristic of nonpolyposis colorectal cancer.', '4c748d6b-84ff-48d7-9b25-6ff0511c51c1': 'Another type of repair mechanism, nucleotide excision repair, is similar to mismatch repair, except that it is used to remove large, bulky damaged bases rather than mismatched ones. The repair enzymes replace abnormal, bulky, bases by making a cut on both the 3′ and 5′ ends of the damaged base. The segment of DNA is removed and replaced with the correctly paired nucleotides by the action of DNA pol. Once the bases are filled in, the remaining gap is sealed with a phosphodiester linkage catalyzed by DNA ligase (figure 10.5(c)).', 'a52185d6-3939-40ad-9a8c-947eaea82106': 'This repair mechanism is often employed when UV exposure causes the formation of pyrimidine dimers (thymine dimers). When exposed to UV light, thymines lying next to each other can form thymine dimers. In normal cells, they are excised and replaced. Xeroderma pigmentosa is a condition in which thymine dimerization from exposure to UV light is not repaired.', 'bb12ea63-1240-4890-87c8-d3a3278c3926': 'Double-stranded breaks are caused by ionizing radiation, such as X-rays or radioactive particles. This can be repaired through two processes: nonhomologous end-joining and homologous recombination. The major difference between these two processes is in nonhomologous end-joining there is direct ligation of the two ends without the need for a DNA template. This can result in some DNA being lost in the process. In contrast, homologous recombination requires a DNA template to repair the break. This allows for restoration of the duplex without a loss of nucleotides.', 'acf27e34-f0e2-4f70-8d3b-be20a9e5b6c0': '10.2 References and resources', '4a9b3ed2-d06c-49ce-9ff5-0368c2ceeae9': '10.3 DNA Replication'}"
Figure 10.6,cell_bio/images/Figure 10.6.jpg,Figure 10.6: Summary of base excision repair. This is a similar process to NER but requires a glycosylase.,"The process of base excision repair (BER) is similar to NER but tends to repair small modifications to individual bases, such as deamination of cytosine to produce uracil. In this process, the aberrant base is detected by a glycosylase that will cleave the N-glycosidic bond joining the base to the deoxyribose sugar. This leaves an apurinic or apyrimidinic site (sugar phosphate backbone lacking a base), which is cleaved by an exonuclease and repaired through a similar process as mentioned above (figure 10.6).","{'d30bcc8b-7428-4537-b5e8-c55fabd567c7': 'The process of base excision repair (BER)\xa0is similar to NER but tends to repair small modifications to individual bases, such as deamination of cytosine to produce uracil. In this process, the aberrant base is detected by a glycosylase that will cleave the N-glycosidic bond joining the base to the deoxyribose sugar. This leaves an apurinic or apyrimidinic site (sugar phosphate backbone lacking a base), which is cleaved by an exonuclease and repaired through a similar process as mentioned above (figure 10.6).', 'bb12ea63-1240-4890-87c8-d3a3278c3926': 'Double-stranded breaks are caused by ionizing radiation, such as X-rays or radioactive particles. This can be repaired through two processes: nonhomologous end-joining and homologous recombination. The major difference between these two processes is in nonhomologous end-joining there is direct ligation of the two ends without the need for a DNA template. This can result in some DNA being lost in the process. In contrast, homologous recombination requires a DNA template to repair the break. This allows for restoration of the duplex without a loss of nucleotides.', 'acf27e34-f0e2-4f70-8d3b-be20a9e5b6c0': '10.2 References and resources', '4a9b3ed2-d06c-49ce-9ff5-0368c2ceeae9': '10.3 DNA Replication'}"
Figure 10.5,cell_bio/images/Figure 10.5.jpg,"Figure 10.5: Comparison on three types of repair: (A) proofreading, (B) mismatch, and (C) nucleotide excision repair.","Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).","{'1bf2c3c1-b4e9-45d9-a41d-c56bacd8ccb4': 'Eukaryotic chromosomes consist of a linear DNA molecule\xa0complexed with protein (histones);\xa0this complex is called chromatin. Histones are evolutionarily conserved proteins that are rich in basic amino acids and form an octamer composed of two molecules of each of four different histones.', 'cde557b8-26ab-43e0-ab5b-935bcdd02d9a': 'The DNA (remember, it is negatively charged because of the phosphate groups) is wrapped tightly around the histone core. This interaction is facilitated through electrostatic interactions. The negatively charged phosphate groups on the DNA backbone are attracted to a positively charged lysine on the exposed surface of histones. This nucleosome is linked to the next one with the help of a linker DNA. This is also known as the “beads on a string” structure. With the help of a fifth histone, a string of nucleosomes is further compacted into a 30 nm fiber, which is the diameter of the structure. Metaphase chromosomes are even further condensed by association with scaffolding proteins. At the metaphase stage, the chromosomes are at their most compact, approximately 700 nm in width (figure 10.4).', '72738197-56e2-4a37-98c5-30962c2676ff': 'In interphase, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. The tightly packaged region is known as heterochromatin, and the less dense region is known as euchromatin.', '9171b2ea-08b5-4d27-aedb-64a9f91a5a9c': 'Heterochromatin usually contains genes that are not expressed\xa0and is found in the regions of the centromere and telomeres.', 'd63eea7e-edcb-4e55-ab24-a9a677064c4b': 'The euchromatin usually contains genes that are transcribed, with DNA packaged around nucleosomes but not further compacted.', '2c4513a4-2a86-4cf9-8931-6cdeb52dbedd': 'Histone tails can be modified through both methylation and acetylation, which will alter the histone:DNA interaction. Histone methylation can have variable impacts on a given gene locus leading to a change in transcription. Histone acetylation relaxes the interactions of histones and DNA by removing the positive charge on lysine residues allowing the DNA to be transcriptionally accessible (euchromatin). DNA methylation, specifically to CpG islands, globally represses transcription. These modifications on histones and DNA\xa0can result in epigenetic influences that have an impact on many biological processes.', '032ca653-9837-4376-bb42-169f4567c217': 'Across the three\xa0billion base pair genome, genes are organized into clusters with only a fraction of the DNA coding for translated products. The remaining DNA was historically considered “junk,”\xa0however, more recently there is a new appreciation for the roles of noncoding DNA regions. Only half of the genome is unique DNA sequence, and only 1.5 percent\xa0codes for mRNA (~20,000 protein-coding genes). The remaining sequence can be categorized as:', '85d55426-c44f-426c-9ed9-bac98d6dd169': '10.1 References and resources', 'e94b1cab-3161-4850-9e0c-731242929910': 'Clark, M. A. Biology, 2nd ed. Houston, TX: OpenStax College, Rice University, 2018, Chapter 14: DNA Structure and Function.', '32a0fa07-bed4-42f6-94c2-6184c6996692': 'Karp, G., and J. G. Patton. Cell and Molecular Biology: Concepts and Experiments, 7th ed. Hoboken, NJ: John Wiley, 2013, Chapter 10: The Nature of the Gene and the Genome, Chapter 12: The Cell Nucleus and the Control of Gene Expression, Chapter 13: DNA Replication.', 'c88b2c4c-3b5e-4b38-8c5a-67684644b5b9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 34, 38–40.', '5cd1ab88-84e4-441e-be49-47194df0ea17': 'Nussbaum, R. L., R. R. McInnes, H. F. Willard, A. Hamosh, and M. W. Thompson. Thompson & Thompson Genetics\xa0 in Medicine, 8th ed. Philadelphia: Saunders/Elsevier, 2016, Chapter 2: The Introduction to the Human Genome.', '720ababc-cfc4-41b0-8650-0e79cccf3fcf': '10.2 DNA Repair', '3b87f707-c0e5-42f9-94bf-1fd8a4ebebab': 'DNA replication is a highly accurate process, but mistakes can occasionally occur, such as a DNA polymerase (DNA pol) inserting a wrong base. Uncorrected mistakes may sometimes lead to serious consequences, such as cancer. Repair mechanisms correct the mistakes. In rare cases, mistakes are not corrected, leading to mutations; in other cases, repair enzymes are themselves mutated or defective.', '77129dfc-e395-4ef2-ae0b-848536a15460': 'Most of the mistakes during DNA replication are promptly corrected by the proofreading ability of DNA polymerase itself. In proofreading, the DNA pol reads the newly added base before adding the next one, so a correction can be made. The polymerase checks whether the newly added base has paired correctly with the base in the template strand. If it is the right base, the next nucleotide is added. If an incorrect base has been added, the enzyme makes a cut at the phosphodiester bond and releases the wrong nucleotide. This is performed by the 3′ exonuclease action of DNA pol. Once the incorrect nucleotide has been removed, it can be replaced by the correct one (figure 10.5(a)).', '054d60a2-fbc6-409b-a40f-109f3eeff57a': 'Errors not addressed during replication are repaired through the process of mismatch repair (figure 10.5(b)). Specific repair enzymes recognize the mispaired nucleotide and excise part of the strand that contains it; the excised region is then resynthesized —\xa0typically during S phase of the cell cycle — and the enzymes involved are those used for DNA replication. If the mismatch remains uncorrected, it may lead to more permanent damage when the mismatched DNA is replicated. Deficiencies in this repair process can result in Lynch syndrome, which is characteristic of nonpolyposis colorectal cancer.', '4c748d6b-84ff-48d7-9b25-6ff0511c51c1': 'Another type of repair mechanism, nucleotide excision repair, is similar to mismatch repair, except that it is used to remove large, bulky damaged bases rather than mismatched ones. The repair enzymes replace abnormal, bulky, bases by making a cut on both the 3′ and 5′ ends of the damaged base. The segment of DNA is removed and replaced with the correctly paired nucleotides by the action of DNA pol. Once the bases are filled in, the remaining gap is sealed with a phosphodiester linkage catalyzed by DNA ligase (figure 10.5(c)).', 'a52185d6-3939-40ad-9a8c-947eaea82106': 'This repair mechanism is often employed when UV exposure causes the formation of pyrimidine dimers (thymine dimers). When exposed to UV light, thymines lying next to each other can form thymine dimers. In normal cells, they are excised and replaced. Xeroderma pigmentosa is a condition in which thymine dimerization from exposure to UV light is not repaired.', 'bb12ea63-1240-4890-87c8-d3a3278c3926': 'Double-stranded breaks are caused by ionizing radiation, such as X-rays or radioactive particles. This can be repaired through two processes: nonhomologous end-joining and homologous recombination. The major difference between these two processes is in nonhomologous end-joining there is direct ligation of the two ends without the need for a DNA template. This can result in some DNA being lost in the process. In contrast, homologous recombination requires a DNA template to repair the break. This allows for restoration of the duplex without a loss of nucleotides.', 'acf27e34-f0e2-4f70-8d3b-be20a9e5b6c0': '10.2 References and resources', '4a9b3ed2-d06c-49ce-9ff5-0368c2ceeae9': '10.3 DNA Replication'}"
Figure 10.6,cell_bio/images/Figure 10.6.jpg,Figure 10.6: Summary of base excision repair. This is a similar process to NER but requires a glycosylase.,"The process of base excision repair (BER) is similar to NER but tends to repair small modifications to individual bases, such as deamination of cytosine to produce uracil. In this process, the aberrant base is detected by a glycosylase that will cleave the N-glycosidic bond joining the base to the deoxyribose sugar. This leaves an apurinic or apyrimidinic site (sugar phosphate backbone lacking a base), which is cleaved by an exonuclease and repaired through a similar process as mentioned above (figure 10.6).","{'d30bcc8b-7428-4537-b5e8-c55fabd567c7': 'The process of base excision repair (BER)\xa0is similar to NER but tends to repair small modifications to individual bases, such as deamination of cytosine to produce uracil. In this process, the aberrant base is detected by a glycosylase that will cleave the N-glycosidic bond joining the base to the deoxyribose sugar. This leaves an apurinic or apyrimidinic site (sugar phosphate backbone lacking a base), which is cleaved by an exonuclease and repaired through a similar process as mentioned above (figure 10.6).', 'bb12ea63-1240-4890-87c8-d3a3278c3926': 'Double-stranded breaks are caused by ionizing radiation, such as X-rays or radioactive particles. This can be repaired through two processes: nonhomologous end-joining and homologous recombination. The major difference between these two processes is in nonhomologous end-joining there is direct ligation of the two ends without the need for a DNA template. This can result in some DNA being lost in the process. In contrast, homologous recombination requires a DNA template to repair the break. This allows for restoration of the duplex without a loss of nucleotides.', 'acf27e34-f0e2-4f70-8d3b-be20a9e5b6c0': '10.2 References and resources', '4a9b3ed2-d06c-49ce-9ff5-0368c2ceeae9': '10.3 DNA Replication'}"
Figure 10.8,cell_bio/images/Figure 10.8.jpg,Figure 10.8: Summary of telomerase activity to fill the overhang on the lagging strand.,"Telomeres comprise repetitive sequences that code for no particular gene. In humans, a six-base-pair sequence, TTAGGG, is repeated 100 to 1,000 times in the telomere regions. In a way, these telomeres protect the genes from getting deleted as cells continue to divide. The telomeres are added to the ends of chromosomes by a separate enzyme, telomerase (figure 10.8), whose discovery helped in the understanding of how these repetitive chromosome ends are maintained. The telomerase enzyme contains a catalytic part and a built-in RNA template. It attaches to the end of the chromosome, and DNA nucleotides complementary to the RNA template are added on the 3′ end of the DNA strand. Once the 3′ end of the lagging strand template is sufficiently elongated, DNA polymerase can add the nucleotides complementary to the ends of the chromosomes. Thus, the ends of the chromosomes are replicated.","{'b836338a-30b9-467d-b839-6febbd9b8b38': 'In eukaryotes, leading strand synthesis continues until the end of the chromosome is reached. On the lagging strand, DNA is synthesized in short stretches, each of which is initiated by a separate primer. When the replication fork reaches the end of the linear chromosome, there is no way to replace the primer on the 5ʼ end of the lagging strand.', '1ecb96a2-a064-417a-907b-3b398a45a465': 'The DNA at the ends of the chromosome thus remains unpaired, and over time these ends, called telomeres, may get progressively shorter as cells continue to divide.', '0c4d05cf-3151-4d2b-a1ea-cdaa10e72b2e': 'Telomeres comprise repetitive sequences that code for no particular gene. In humans, a six-base-pair sequence, TTAGGG, is repeated 100 to 1,000 times in the telomere regions. In a way, these telomeres protect the genes from getting deleted as cells continue to divide. The telomeres are added to the ends of chromosomes by a separate enzyme, telomerase (figure 10.8), whose discovery helped in the understanding of how these repetitive chromosome ends are maintained. The telomerase enzyme contains a catalytic part and a built-in RNA template. It attaches to the end of the chromosome, and DNA nucleotides complementary to the RNA template are added on the 3′ end of the DNA strand. Once the 3′ end of the lagging strand template is sufficiently elongated, DNA polymerase can add the nucleotides complementary to the ends of the chromosomes. Thus, the ends of the chromosomes are replicated.', '18bfb410-5b44-49a3-8858-d9809a310f4f': 'Table 10.1: Prokaryotic DNA replication: enzymes and their function.', '421c5f70-1cd3-4aa0-83f5-91a8ea5c419d': 'Table 10.2: Difference between prokaryotic and eukaryotic replication.', '65bcb211-b8e5-49d4-a875-0ba5420fb5f3': '10.3 References and resources', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 10.7,cell_bio/images/Figure 10.7.jpg,,Figure 10.7: Summary of DNA replication.,"{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 10.8,cell_bio/images/Figure 10.8.jpg,Figure 10.8: Summary of telomerase activity to fill the overhang on the lagging strand.,"Telomeres comprise repetitive sequences that code for no particular gene. In humans, a six-base-pair sequence, TTAGGG, is repeated 100 to 1,000 times in the telomere regions. In a way, these telomeres protect the genes from getting deleted as cells continue to divide. The telomeres are added to the ends of chromosomes by a separate enzyme, telomerase (figure 10.8), whose discovery helped in the understanding of how these repetitive chromosome ends are maintained. The telomerase enzyme contains a catalytic part and a built-in RNA template. It attaches to the end of the chromosome, and DNA nucleotides complementary to the RNA template are added on the 3′ end of the DNA strand. Once the 3′ end of the lagging strand template is sufficiently elongated, DNA polymerase can add the nucleotides complementary to the ends of the chromosomes. Thus, the ends of the chromosomes are replicated.","{'b836338a-30b9-467d-b839-6febbd9b8b38': 'In eukaryotes, leading strand synthesis continues until the end of the chromosome is reached. On the lagging strand, DNA is synthesized in short stretches, each of which is initiated by a separate primer. When the replication fork reaches the end of the linear chromosome, there is no way to replace the primer on the 5ʼ end of the lagging strand.', '1ecb96a2-a064-417a-907b-3b398a45a465': 'The DNA at the ends of the chromosome thus remains unpaired, and over time these ends, called telomeres, may get progressively shorter as cells continue to divide.', '0c4d05cf-3151-4d2b-a1ea-cdaa10e72b2e': 'Telomeres comprise repetitive sequences that code for no particular gene. In humans, a six-base-pair sequence, TTAGGG, is repeated 100 to 1,000 times in the telomere regions. In a way, these telomeres protect the genes from getting deleted as cells continue to divide. The telomeres are added to the ends of chromosomes by a separate enzyme, telomerase (figure 10.8), whose discovery helped in the understanding of how these repetitive chromosome ends are maintained. The telomerase enzyme contains a catalytic part and a built-in RNA template. It attaches to the end of the chromosome, and DNA nucleotides complementary to the RNA template are added on the 3′ end of the DNA strand. Once the 3′ end of the lagging strand template is sufficiently elongated, DNA polymerase can add the nucleotides complementary to the ends of the chromosomes. Thus, the ends of the chromosomes are replicated.', '18bfb410-5b44-49a3-8858-d9809a310f4f': 'Table 10.1: Prokaryotic DNA replication: enzymes and their function.', '421c5f70-1cd3-4aa0-83f5-91a8ea5c419d': 'Table 10.2: Difference between prokaryotic and eukaryotic replication.', '65bcb211-b8e5-49d4-a875-0ba5420fb5f3': '10.3 References and resources', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 9.2,cell_bio/images/Figure 9.2.jpg,"Figure 9.2: Fructose metabolism and reaction by aldolase B. Deficiencies in aldolase B can result in hereditary fructose intolerance, while deficiencies in frutokinase can result in essential fructosuria.","Galactose is consumed principally as lactose, which is cleaved to galactose and glucose in the intestine. Galactose is subsequently phosphorylated to galactose 1-phosphate by galactokinase (primarily in the liver). Following phosphorylation, galactose 1-phosphate is activated to a uridine diphosphate (UDP)-sugar by galactosyl uridylyltransferase (GALT). The metabolic pathway subsequently generates glucose 1-phosphate, which enters into the glycolytic pathway (figure 9.2)","{'d960cb95-529b-4963-b69f-4dcb9459192d': 'Galactose is consumed principally as lactose, which is cleaved to galactose and glucose in the intestine. Galactose is subsequently phosphorylated to galactose 1-phosphate by galactokinase (primarily in the liver). Following phosphorylation, galactose 1-phosphate is activated to a uridine diphosphate (UDP)-sugar by galactosyl uridylyltransferase (GALT). The metabolic pathway subsequently generates glucose 1-phosphate, which enters into the glycolytic pathway (figure 9.2)', 'f7d31efc-20ae-405f-8c75-520317427e34': 'Classical galactosemia, a deficiency of galactosyl uridylyltransferase (GALT), results in the accumulation of galactose 1-phosphate in the liver and the inhibition of hepatic glycogen metabolism and other pathways that require UDP-sugars. Cataracts can occur from the accumulation of galactose in the blood, which is converted to galactitol (the sugar alcohol of galactose) in the lens of the eye.', '38dbf470-9cba-4cb2-b3f6-de7102101fe4': 'The accumulating galactose 1-phosphate is especially toxic for the liver, kidneys, and central nervous system. If left untreated, the disease is fatal due to complications such as\xa0gram-negative sepsis or hepatic and renal failure. The absence of GALT activity can be detected any time after birth and screened for as part of newborn screening. It is essential to obtain results promptly, because children with classic galactosemia can have a life-threatening crisis within the first few days after birth. Infants with a positive result are placed on a lactose-free formula, and confirmatory testing is accomplished by measuring specific metabolite concentrations and enzyme activity in erythrocytes.', 'e6688b43-614a-4a08-8847-8cff0bc57be7': 'Nonclassical galactosemia causes fewer medical complications and presents with a different pattern of symptoms. Presentations can involve cataracts, delayed development, and kidney problems.', 'da69a570-9c31-4fb8-8519-e78a67174c64': '9.1 References and resources', '9ed65514-c630-4d8b-b557-1b39c172f69a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 12: Metabolism of Monosaccharides and Disaccharides, Chapter 23: Effects of Insulin and Glucagon: Section IV.', 'b70d1af8-929d-41e7-8deb-bc1ffa614d5d': 'Le, T., and V.\xa0 Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72, 80–81.', '66f90ae8-b9e6-44ce-aa09-e2263b9d2f89': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 22: Generation of ATP from Glucose, Fructose and Galactose, Chapter 33: Ethanol Metabolism.', 'ad0a0b6f-cd4c-4887-adef-dc57c8f882b3': '9.2 Alcohol Metabolism', '1275b4bf-961d-4bc3-89b9-35847742d9cf': 'Metabolism of alcohol occurs primarily in the liver through two different oxidative pathways. The activity of each pathway depends on the ethanol concentration and the frequency of ethanol consumption.', 'c3ee01a5-61c6-437a-a5b2-ddb94f82787d': 'At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria\xa0by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.'}"
Figure 9.1,cell_bio/images/Figure 9.1.jpg,,Figure 9.1: Convergence of fructose and glucose metabolism.,"{'f7d31efc-20ae-405f-8c75-520317427e34': 'Classical galactosemia, a deficiency of galactosyl uridylyltransferase (GALT), results in the accumulation of galactose 1-phosphate in the liver and the inhibition of hepatic glycogen metabolism and other pathways that require UDP-sugars. Cataracts can occur from the accumulation of galactose in the blood, which is converted to galactitol (the sugar alcohol of galactose) in the lens of the eye.', '38dbf470-9cba-4cb2-b3f6-de7102101fe4': 'The accumulating galactose 1-phosphate is especially toxic for the liver, kidneys, and central nervous system. If left untreated, the disease is fatal due to complications such as\xa0gram-negative sepsis or hepatic and renal failure. The absence of GALT activity can be detected any time after birth and screened for as part of newborn screening. It is essential to obtain results promptly, because children with classic galactosemia can have a life-threatening crisis within the first few days after birth. Infants with a positive result are placed on a lactose-free formula, and confirmatory testing is accomplished by measuring specific metabolite concentrations and enzyme activity in erythrocytes.', 'e6688b43-614a-4a08-8847-8cff0bc57be7': 'Nonclassical galactosemia causes fewer medical complications and presents with a different pattern of symptoms. Presentations can involve cataracts, delayed development, and kidney problems.', 'da69a570-9c31-4fb8-8519-e78a67174c64': '9.1 References and resources', '9ed65514-c630-4d8b-b557-1b39c172f69a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 12: Metabolism of Monosaccharides and Disaccharides, Chapter 23: Effects of Insulin and Glucagon: Section IV.', 'b70d1af8-929d-41e7-8deb-bc1ffa614d5d': 'Le, T., and V.\xa0 Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72, 80–81.', '66f90ae8-b9e6-44ce-aa09-e2263b9d2f89': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 22: Generation of ATP from Glucose, Fructose and Galactose, Chapter 33: Ethanol Metabolism.', 'ad0a0b6f-cd4c-4887-adef-dc57c8f882b3': '9.2 Alcohol Metabolism', '1275b4bf-961d-4bc3-89b9-35847742d9cf': 'Metabolism of alcohol occurs primarily in the liver through two different oxidative pathways. The activity of each pathway depends on the ethanol concentration and the frequency of ethanol consumption.', 'c3ee01a5-61c6-437a-a5b2-ddb94f82787d': 'At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria\xa0by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.'}"
Figure 9.2,cell_bio/images/Figure 9.2.jpg,"Figure 9.2: Fructose metabolism and reaction by aldolase B. Deficiencies in aldolase B can result in hereditary fructose intolerance, while deficiencies in frutokinase can result in essential fructosuria.","Galactose is consumed principally as lactose, which is cleaved to galactose and glucose in the intestine. Galactose is subsequently phosphorylated to galactose 1-phosphate by galactokinase (primarily in the liver). Following phosphorylation, galactose 1-phosphate is activated to a uridine diphosphate (UDP)-sugar by galactosyl uridylyltransferase (GALT). The metabolic pathway subsequently generates glucose 1-phosphate, which enters into the glycolytic pathway (figure 9.2)","{'d960cb95-529b-4963-b69f-4dcb9459192d': 'Galactose is consumed principally as lactose, which is cleaved to galactose and glucose in the intestine. Galactose is subsequently phosphorylated to galactose 1-phosphate by galactokinase (primarily in the liver). Following phosphorylation, galactose 1-phosphate is activated to a uridine diphosphate (UDP)-sugar by galactosyl uridylyltransferase (GALT). The metabolic pathway subsequently generates glucose 1-phosphate, which enters into the glycolytic pathway (figure 9.2)', 'f7d31efc-20ae-405f-8c75-520317427e34': 'Classical galactosemia, a deficiency of galactosyl uridylyltransferase (GALT), results in the accumulation of galactose 1-phosphate in the liver and the inhibition of hepatic glycogen metabolism and other pathways that require UDP-sugars. Cataracts can occur from the accumulation of galactose in the blood, which is converted to galactitol (the sugar alcohol of galactose) in the lens of the eye.', '38dbf470-9cba-4cb2-b3f6-de7102101fe4': 'The accumulating galactose 1-phosphate is especially toxic for the liver, kidneys, and central nervous system. If left untreated, the disease is fatal due to complications such as\xa0gram-negative sepsis or hepatic and renal failure. The absence of GALT activity can be detected any time after birth and screened for as part of newborn screening. It is essential to obtain results promptly, because children with classic galactosemia can have a life-threatening crisis within the first few days after birth. Infants with a positive result are placed on a lactose-free formula, and confirmatory testing is accomplished by measuring specific metabolite concentrations and enzyme activity in erythrocytes.', 'e6688b43-614a-4a08-8847-8cff0bc57be7': 'Nonclassical galactosemia causes fewer medical complications and presents with a different pattern of symptoms. Presentations can involve cataracts, delayed development, and kidney problems.', 'da69a570-9c31-4fb8-8519-e78a67174c64': '9.1 References and resources', '9ed65514-c630-4d8b-b557-1b39c172f69a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 12: Metabolism of Monosaccharides and Disaccharides, Chapter 23: Effects of Insulin and Glucagon: Section IV.', 'b70d1af8-929d-41e7-8deb-bc1ffa614d5d': 'Le, T., and V.\xa0 Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72, 80–81.', '66f90ae8-b9e6-44ce-aa09-e2263b9d2f89': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 22: Generation of ATP from Glucose, Fructose and Galactose, Chapter 33: Ethanol Metabolism.', 'ad0a0b6f-cd4c-4887-adef-dc57c8f882b3': '9.2 Alcohol Metabolism', '1275b4bf-961d-4bc3-89b9-35847742d9cf': 'Metabolism of alcohol occurs primarily in the liver through two different oxidative pathways. The activity of each pathway depends on the ethanol concentration and the frequency of ethanol consumption.', 'c3ee01a5-61c6-437a-a5b2-ddb94f82787d': 'At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria\xa0by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.'}"
Figure 9.3,cell_bio/images/Figure 9.3.jpg,,"Figure 9.3: Galactose metabolism; glucose 6-phosphate is converted to glucose 1-phosphate, which enters the pathway.","{'f7d31efc-20ae-405f-8c75-520317427e34': 'Classical galactosemia, a deficiency of galactosyl uridylyltransferase (GALT), results in the accumulation of galactose 1-phosphate in the liver and the inhibition of hepatic glycogen metabolism and other pathways that require UDP-sugars. Cataracts can occur from the accumulation of galactose in the blood, which is converted to galactitol (the sugar alcohol of galactose) in the lens of the eye.', '38dbf470-9cba-4cb2-b3f6-de7102101fe4': 'The accumulating galactose 1-phosphate is especially toxic for the liver, kidneys, and central nervous system. If left untreated, the disease is fatal due to complications such as\xa0gram-negative sepsis or hepatic and renal failure. The absence of GALT activity can be detected any time after birth and screened for as part of newborn screening. It is essential to obtain results promptly, because children with classic galactosemia can have a life-threatening crisis within the first few days after birth. Infants with a positive result are placed on a lactose-free formula, and confirmatory testing is accomplished by measuring specific metabolite concentrations and enzyme activity in erythrocytes.', 'e6688b43-614a-4a08-8847-8cff0bc57be7': 'Nonclassical galactosemia causes fewer medical complications and presents with a different pattern of symptoms. Presentations can involve cataracts, delayed development, and kidney problems.', 'da69a570-9c31-4fb8-8519-e78a67174c64': '9.1 References and resources', '9ed65514-c630-4d8b-b557-1b39c172f69a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 12: Metabolism of Monosaccharides and Disaccharides, Chapter 23: Effects of Insulin and Glucagon: Section IV.', 'b70d1af8-929d-41e7-8deb-bc1ffa614d5d': 'Le, T., and V.\xa0 Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72, 80–81.', '66f90ae8-b9e6-44ce-aa09-e2263b9d2f89': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 22: Generation of ATP from Glucose, Fructose and Galactose, Chapter 33: Ethanol Metabolism.', 'ad0a0b6f-cd4c-4887-adef-dc57c8f882b3': '9.2 Alcohol Metabolism', '1275b4bf-961d-4bc3-89b9-35847742d9cf': 'Metabolism of alcohol occurs primarily in the liver through two different oxidative pathways. The activity of each pathway depends on the ethanol concentration and the frequency of ethanol consumption.', 'c3ee01a5-61c6-437a-a5b2-ddb94f82787d': 'At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria\xa0by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.'}"
Figure 9.4,cell_bio/images/Figure 9.4.jpg,,Figure 9.4: Comparison of classical and nonclassical galatosemia.,"{'f7d31efc-20ae-405f-8c75-520317427e34': 'Classical galactosemia, a deficiency of galactosyl uridylyltransferase (GALT), results in the accumulation of galactose 1-phosphate in the liver and the inhibition of hepatic glycogen metabolism and other pathways that require UDP-sugars. Cataracts can occur from the accumulation of galactose in the blood, which is converted to galactitol (the sugar alcohol of galactose) in the lens of the eye.', '38dbf470-9cba-4cb2-b3f6-de7102101fe4': 'The accumulating galactose 1-phosphate is especially toxic for the liver, kidneys, and central nervous system. If left untreated, the disease is fatal due to complications such as\xa0gram-negative sepsis or hepatic and renal failure. The absence of GALT activity can be detected any time after birth and screened for as part of newborn screening. It is essential to obtain results promptly, because children with classic galactosemia can have a life-threatening crisis within the first few days after birth. Infants with a positive result are placed on a lactose-free formula, and confirmatory testing is accomplished by measuring specific metabolite concentrations and enzyme activity in erythrocytes.', 'e6688b43-614a-4a08-8847-8cff0bc57be7': 'Nonclassical galactosemia causes fewer medical complications and presents with a different pattern of symptoms. Presentations can involve cataracts, delayed development, and kidney problems.', 'da69a570-9c31-4fb8-8519-e78a67174c64': '9.1 References and resources', '9ed65514-c630-4d8b-b557-1b39c172f69a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 12: Metabolism of Monosaccharides and Disaccharides, Chapter 23: Effects of Insulin and Glucagon: Section IV.', 'b70d1af8-929d-41e7-8deb-bc1ffa614d5d': 'Le, T., and V.\xa0 Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72, 80–81.', '66f90ae8-b9e6-44ce-aa09-e2263b9d2f89': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 22: Generation of ATP from Glucose, Fructose and Galactose, Chapter 33: Ethanol Metabolism.', 'ad0a0b6f-cd4c-4887-adef-dc57c8f882b3': '9.2 Alcohol Metabolism', '1275b4bf-961d-4bc3-89b9-35847742d9cf': 'Metabolism of alcohol occurs primarily in the liver through two different oxidative pathways. The activity of each pathway depends on the ethanol concentration and the frequency of ethanol consumption.', 'c3ee01a5-61c6-437a-a5b2-ddb94f82787d': 'At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria\xa0by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.'}"
Figure 9.5,cell_bio/images/Figure 9.5.jpg,"Figure 9.5: Overview of ethanol metabolism. The pathway spans the cytosol and the mitochondria, and NADH is produced in both steps of the pathway.","At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.","{'f7d31efc-20ae-405f-8c75-520317427e34': 'Classical galactosemia, a deficiency of galactosyl uridylyltransferase (GALT), results in the accumulation of galactose 1-phosphate in the liver and the inhibition of hepatic glycogen metabolism and other pathways that require UDP-sugars. Cataracts can occur from the accumulation of galactose in the blood, which is converted to galactitol (the sugar alcohol of galactose) in the lens of the eye.', '38dbf470-9cba-4cb2-b3f6-de7102101fe4': 'The accumulating galactose 1-phosphate is especially toxic for the liver, kidneys, and central nervous system. If left untreated, the disease is fatal due to complications such as\xa0gram-negative sepsis or hepatic and renal failure. The absence of GALT activity can be detected any time after birth and screened for as part of newborn screening. It is essential to obtain results promptly, because children with classic galactosemia can have a life-threatening crisis within the first few days after birth. Infants with a positive result are placed on a lactose-free formula, and confirmatory testing is accomplished by measuring specific metabolite concentrations and enzyme activity in erythrocytes.', 'e6688b43-614a-4a08-8847-8cff0bc57be7': 'Nonclassical galactosemia causes fewer medical complications and presents with a different pattern of symptoms. Presentations can involve cataracts, delayed development, and kidney problems.', 'da69a570-9c31-4fb8-8519-e78a67174c64': '9.1 References and resources', '9ed65514-c630-4d8b-b557-1b39c172f69a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 12: Metabolism of Monosaccharides and Disaccharides, Chapter 23: Effects of Insulin and Glucagon: Section IV.', 'b70d1af8-929d-41e7-8deb-bc1ffa614d5d': 'Le, T., and V.\xa0 Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72, 80–81.', '66f90ae8-b9e6-44ce-aa09-e2263b9d2f89': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 22: Generation of ATP from Glucose, Fructose and Galactose, Chapter 33: Ethanol Metabolism.', 'ad0a0b6f-cd4c-4887-adef-dc57c8f882b3': '9.2 Alcohol Metabolism', '1275b4bf-961d-4bc3-89b9-35847742d9cf': 'Metabolism of alcohol occurs primarily in the liver through two different oxidative pathways. The activity of each pathway depends on the ethanol concentration and the frequency of ethanol consumption.', 'c3ee01a5-61c6-437a-a5b2-ddb94f82787d': 'At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria\xa0by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.', 'e270fb83-e8d2-4a00-ab1c-8dfcdda94640': 'At each step in ethanol oxidation, NADH is generated in both the mitochondrial and cytosolic compartments (figure 9.5). This can have major metabolic ramifications depending on the underlying metabolic environment (figure 9.7).', 'eb469236-4d0a-482d-9468-5006df6d0d00': 'Although the MEOS system does not impact the NADH/NAD+ ratio, that is not to suggest that induction of this system is without metabolic consequences. Induction of the P450 system can negatively impact the metabolism of other drugs causing serious side effects. One example of this is altered metabolism of acetaminophen (Tylenol). Acetaminophen can be glucuronylated or sulfated in the liver for safe excretion by the kidney. However, the cytochrome P450 system can metabolize acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI), which requires conjugation with glutathione prior to excretion. The enzyme that produces NAPQI, CYP2E1, is induced by alcohol through the MEOS. Thus, individuals who chronically abuse alcohol have increased sensitivity to acetaminophen toxicity because a higher percentage of acetaminophen metabolism is directed toward NAPQI, compared with an individual with low levels of CYP2E1.', 'de0bd9f2-bfa0-4c90-b99b-d70ad56769a9': 'Ethanol is also an inhibitor of the phenobarbital-oxidizing P450 system. When large amounts of ethanol are consumed, the inactivation of phenobarbital is directly or indirectly inhibited. Therefore, when high doses of phenobarbital and ethanol are consumed at the same time, toxic levels of the barbiturate can accumulate in the blood.', '34c98be3-f26a-42b4-9cda-68e2255d244c': '9.2 References and resources', 'a48032a6-dfbe-4e21-9004-eba417e95296': 'Lieberman M, Peet A. Figure 9.7 Clinical consequences of alcoholism. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 709. Figure 33.6 Acute effects of ethanol metabolism on lipid metabolism in the liver. 2017.', '52db8b30-a982-4fe1-a506-2eafd8f3fcac': 'Lieberman M, Peet A. Figure 9.8 Ethanol detoxification by MEOS. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 704. Figure 33.3 The reaction catalyzed by the microsomal ethanol-oxidizing system (MEOS; which includes CYP2E1) in the endoplasmic reticulum (ER). 2017. Chemical structure by Henry Jakubowski.'}"
Figure 9.5,cell_bio/images/Figure 9.5.jpg,"Figure 9.5: Overview of ethanol metabolism. The pathway spans the cytosol and the mitochondria, and NADH is produced in both steps of the pathway.","At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.","{'f7d31efc-20ae-405f-8c75-520317427e34': 'Classical galactosemia, a deficiency of galactosyl uridylyltransferase (GALT), results in the accumulation of galactose 1-phosphate in the liver and the inhibition of hepatic glycogen metabolism and other pathways that require UDP-sugars. Cataracts can occur from the accumulation of galactose in the blood, which is converted to galactitol (the sugar alcohol of galactose) in the lens of the eye.', '38dbf470-9cba-4cb2-b3f6-de7102101fe4': 'The accumulating galactose 1-phosphate is especially toxic for the liver, kidneys, and central nervous system. If left untreated, the disease is fatal due to complications such as\xa0gram-negative sepsis or hepatic and renal failure. The absence of GALT activity can be detected any time after birth and screened for as part of newborn screening. It is essential to obtain results promptly, because children with classic galactosemia can have a life-threatening crisis within the first few days after birth. Infants with a positive result are placed on a lactose-free formula, and confirmatory testing is accomplished by measuring specific metabolite concentrations and enzyme activity in erythrocytes.', 'e6688b43-614a-4a08-8847-8cff0bc57be7': 'Nonclassical galactosemia causes fewer medical complications and presents with a different pattern of symptoms. Presentations can involve cataracts, delayed development, and kidney problems.', 'da69a570-9c31-4fb8-8519-e78a67174c64': '9.1 References and resources', '9ed65514-c630-4d8b-b557-1b39c172f69a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 12: Metabolism of Monosaccharides and Disaccharides, Chapter 23: Effects of Insulin and Glucagon: Section IV.', 'b70d1af8-929d-41e7-8deb-bc1ffa614d5d': 'Le, T., and V.\xa0 Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72, 80–81.', '66f90ae8-b9e6-44ce-aa09-e2263b9d2f89': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 22: Generation of ATP from Glucose, Fructose and Galactose, Chapter 33: Ethanol Metabolism.', 'ad0a0b6f-cd4c-4887-adef-dc57c8f882b3': '9.2 Alcohol Metabolism', '1275b4bf-961d-4bc3-89b9-35847742d9cf': 'Metabolism of alcohol occurs primarily in the liver through two different oxidative pathways. The activity of each pathway depends on the ethanol concentration and the frequency of ethanol consumption.', 'c3ee01a5-61c6-437a-a5b2-ddb94f82787d': 'At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria\xa0by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.', 'e270fb83-e8d2-4a00-ab1c-8dfcdda94640': 'At each step in ethanol oxidation, NADH is generated in both the mitochondrial and cytosolic compartments (figure 9.5). This can have major metabolic ramifications depending on the underlying metabolic environment (figure 9.7).', 'eb469236-4d0a-482d-9468-5006df6d0d00': 'Although the MEOS system does not impact the NADH/NAD+ ratio, that is not to suggest that induction of this system is without metabolic consequences. Induction of the P450 system can negatively impact the metabolism of other drugs causing serious side effects. One example of this is altered metabolism of acetaminophen (Tylenol). Acetaminophen can be glucuronylated or sulfated in the liver for safe excretion by the kidney. However, the cytochrome P450 system can metabolize acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI), which requires conjugation with glutathione prior to excretion. The enzyme that produces NAPQI, CYP2E1, is induced by alcohol through the MEOS. Thus, individuals who chronically abuse alcohol have increased sensitivity to acetaminophen toxicity because a higher percentage of acetaminophen metabolism is directed toward NAPQI, compared with an individual with low levels of CYP2E1.', 'de0bd9f2-bfa0-4c90-b99b-d70ad56769a9': 'Ethanol is also an inhibitor of the phenobarbital-oxidizing P450 system. When large amounts of ethanol are consumed, the inactivation of phenobarbital is directly or indirectly inhibited. Therefore, when high doses of phenobarbital and ethanol are consumed at the same time, toxic levels of the barbiturate can accumulate in the blood.', '34c98be3-f26a-42b4-9cda-68e2255d244c': '9.2 References and resources', 'a48032a6-dfbe-4e21-9004-eba417e95296': 'Lieberman M, Peet A. Figure 9.7 Clinical consequences of alcoholism. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 709. Figure 33.6 Acute effects of ethanol metabolism on lipid metabolism in the liver. 2017.', '52db8b30-a982-4fe1-a506-2eafd8f3fcac': 'Lieberman M, Peet A. Figure 9.8 Ethanol detoxification by MEOS. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 704. Figure 33.3 The reaction catalyzed by the microsomal ethanol-oxidizing system (MEOS; which includes CYP2E1) in the endoplasmic reticulum (ER). 2017. Chemical structure by Henry Jakubowski.'}"
Figure 9.7,cell_bio/images/Figure 9.7.jpg,Figure 9.7: Clinical consequences of alcoholism.,"At higher concentrations of ethanol, the microsomal ethanol oxidizing system (MEOS) becomes activated (figure 9.7; label 9). This pathway consists of a series of cytochrome P450 enzymes, which have a relatively high Km for ethanol and are located in the hepatic smooth endoplasmic reticulum (SER). This microsomal-ethanol oxidizing system also detoxifies drugs such as barbiturates (figure 9.8).","{'92209e04-09ea-4e80-8a0b-5bd3bdbd1df4': 'At higher concentrations of ethanol, the microsomal ethanol oxidizing system (MEOS) becomes activated (figure 9.7; label 9). This pathway consists of a series of cytochrome P450 enzymes, which have a relatively high Km for ethanol and are located in the hepatic smooth endoplasmic reticulum (SER). This microsomal-ethanol oxidizing system also detoxifies drugs such as barbiturates (figure 9.8).', 'eb469236-4d0a-482d-9468-5006df6d0d00': 'Although the MEOS system does not impact the NADH/NAD+ ratio, that is not to suggest that induction of this system is without metabolic consequences. Induction of the P450 system can negatively impact the metabolism of other drugs causing serious side effects. One example of this is altered metabolism of acetaminophen (Tylenol). Acetaminophen can be glucuronylated or sulfated in the liver for safe excretion by the kidney. However, the cytochrome P450 system can metabolize acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI), which requires conjugation with glutathione prior to excretion. The enzyme that produces NAPQI, CYP2E1, is induced by alcohol through the MEOS. Thus, individuals who chronically abuse alcohol have increased sensitivity to acetaminophen toxicity because a higher percentage of acetaminophen metabolism is directed toward NAPQI, compared with an individual with low levels of CYP2E1.', 'de0bd9f2-bfa0-4c90-b99b-d70ad56769a9': 'Ethanol is also an inhibitor of the phenobarbital-oxidizing P450 system. When large amounts of ethanol are consumed, the inactivation of phenobarbital is directly or indirectly inhibited. Therefore, when high doses of phenobarbital and ethanol are consumed at the same time, toxic levels of the barbiturate can accumulate in the blood.', '34c98be3-f26a-42b4-9cda-68e2255d244c': '9.2 References and resources', 'a48032a6-dfbe-4e21-9004-eba417e95296': 'Lieberman M, Peet A. Figure 9.7 Clinical consequences of alcoholism. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 709. Figure 33.6 Acute effects of ethanol metabolism on lipid metabolism in the liver. 2017.', '52db8b30-a982-4fe1-a506-2eafd8f3fcac': 'Lieberman M, Peet A. Figure 9.8 Ethanol detoxification by MEOS. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 704. Figure 33.3 The reaction catalyzed by the microsomal ethanol-oxidizing system (MEOS; which includes CYP2E1) in the endoplasmic reticulum (ER). 2017. Chemical structure by Henry Jakubowski.'}"
Figure 9.5,cell_bio/images/Figure 9.5.jpg,"Figure 9.5: Overview of ethanol metabolism. The pathway spans the cytosol and the mitochondria, and NADH is produced in both steps of the pathway.","At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.","{'f7d31efc-20ae-405f-8c75-520317427e34': 'Classical galactosemia, a deficiency of galactosyl uridylyltransferase (GALT), results in the accumulation of galactose 1-phosphate in the liver and the inhibition of hepatic glycogen metabolism and other pathways that require UDP-sugars. Cataracts can occur from the accumulation of galactose in the blood, which is converted to galactitol (the sugar alcohol of galactose) in the lens of the eye.', '38dbf470-9cba-4cb2-b3f6-de7102101fe4': 'The accumulating galactose 1-phosphate is especially toxic for the liver, kidneys, and central nervous system. If left untreated, the disease is fatal due to complications such as\xa0gram-negative sepsis or hepatic and renal failure. The absence of GALT activity can be detected any time after birth and screened for as part of newborn screening. It is essential to obtain results promptly, because children with classic galactosemia can have a life-threatening crisis within the first few days after birth. Infants with a positive result are placed on a lactose-free formula, and confirmatory testing is accomplished by measuring specific metabolite concentrations and enzyme activity in erythrocytes.', 'e6688b43-614a-4a08-8847-8cff0bc57be7': 'Nonclassical galactosemia causes fewer medical complications and presents with a different pattern of symptoms. Presentations can involve cataracts, delayed development, and kidney problems.', 'da69a570-9c31-4fb8-8519-e78a67174c64': '9.1 References and resources', '9ed65514-c630-4d8b-b557-1b39c172f69a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 12: Metabolism of Monosaccharides and Disaccharides, Chapter 23: Effects of Insulin and Glucagon: Section IV.', 'b70d1af8-929d-41e7-8deb-bc1ffa614d5d': 'Le, T., and V.\xa0 Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72, 80–81.', '66f90ae8-b9e6-44ce-aa09-e2263b9d2f89': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 22: Generation of ATP from Glucose, Fructose and Galactose, Chapter 33: Ethanol Metabolism.', 'ad0a0b6f-cd4c-4887-adef-dc57c8f882b3': '9.2 Alcohol Metabolism', '1275b4bf-961d-4bc3-89b9-35847742d9cf': 'Metabolism of alcohol occurs primarily in the liver through two different oxidative pathways. The activity of each pathway depends on the ethanol concentration and the frequency of ethanol consumption.', 'c3ee01a5-61c6-437a-a5b2-ddb94f82787d': 'At low concentrations, oxidation of ethanol is a two-step process that occurs in both the cytosol and the mitochondria (figure 9.5). The first step of the reaction by alcohol dehydrogenase (ADH) occurs in the cytosol and produces acetaldehyde. Acetaldehyde is converted into acetate in the mitochondria\xa0by acetaldehyde dehydrogenase (ALDH) and can be transported in the blood to be used as an energy source for peripheral tissues (figure 9.5). The acetate can be converted to acetyl-CoA by acetyl-CoA synthetase (figure 9.6), and this will be oxidized in the TCA cycle. Each step in the oxidation of ethanol produces NADH, which increases the ratio of NADH/NAD+. The increase in this ratio can alter metabolism of other substrates and cause metabolic dysfunction, which will be discussed below.', 'e270fb83-e8d2-4a00-ab1c-8dfcdda94640': 'At each step in ethanol oxidation, NADH is generated in both the mitochondrial and cytosolic compartments (figure 9.5). This can have major metabolic ramifications depending on the underlying metabolic environment (figure 9.7).', 'eb469236-4d0a-482d-9468-5006df6d0d00': 'Although the MEOS system does not impact the NADH/NAD+ ratio, that is not to suggest that induction of this system is without metabolic consequences. Induction of the P450 system can negatively impact the metabolism of other drugs causing serious side effects. One example of this is altered metabolism of acetaminophen (Tylenol). Acetaminophen can be glucuronylated or sulfated in the liver for safe excretion by the kidney. However, the cytochrome P450 system can metabolize acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI), which requires conjugation with glutathione prior to excretion. The enzyme that produces NAPQI, CYP2E1, is induced by alcohol through the MEOS. Thus, individuals who chronically abuse alcohol have increased sensitivity to acetaminophen toxicity because a higher percentage of acetaminophen metabolism is directed toward NAPQI, compared with an individual with low levels of CYP2E1.', 'de0bd9f2-bfa0-4c90-b99b-d70ad56769a9': 'Ethanol is also an inhibitor of the phenobarbital-oxidizing P450 system. When large amounts of ethanol are consumed, the inactivation of phenobarbital is directly or indirectly inhibited. Therefore, when high doses of phenobarbital and ethanol are consumed at the same time, toxic levels of the barbiturate can accumulate in the blood.', '34c98be3-f26a-42b4-9cda-68e2255d244c': '9.2 References and resources', 'a48032a6-dfbe-4e21-9004-eba417e95296': 'Lieberman M, Peet A. Figure 9.7 Clinical consequences of alcoholism. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 709. Figure 33.6 Acute effects of ethanol metabolism on lipid metabolism in the liver. 2017.', '52db8b30-a982-4fe1-a506-2eafd8f3fcac': 'Lieberman M, Peet A. Figure 9.8 Ethanol detoxification by MEOS. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 704. Figure 33.3 The reaction catalyzed by the microsomal ethanol-oxidizing system (MEOS; which includes CYP2E1) in the endoplasmic reticulum (ER). 2017. Chemical structure by Henry Jakubowski.'}"
Figure 9.6,cell_bio/images/Figure 9.6.jpg,,Figure 9.6: Overview of alcohol metabolism.,"{'eb469236-4d0a-482d-9468-5006df6d0d00': 'Although the MEOS system does not impact the NADH/NAD+ ratio, that is not to suggest that induction of this system is without metabolic consequences. Induction of the P450 system can negatively impact the metabolism of other drugs causing serious side effects. One example of this is altered metabolism of acetaminophen (Tylenol). Acetaminophen can be glucuronylated or sulfated in the liver for safe excretion by the kidney. However, the cytochrome P450 system can metabolize acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI), which requires conjugation with glutathione prior to excretion. The enzyme that produces NAPQI, CYP2E1, is induced by alcohol through the MEOS. Thus, individuals who chronically abuse alcohol have increased sensitivity to acetaminophen toxicity because a higher percentage of acetaminophen metabolism is directed toward NAPQI, compared with an individual with low levels of CYP2E1.', 'de0bd9f2-bfa0-4c90-b99b-d70ad56769a9': 'Ethanol is also an inhibitor of the phenobarbital-oxidizing P450 system. When large amounts of ethanol are consumed, the inactivation of phenobarbital is directly or indirectly inhibited. Therefore, when high doses of phenobarbital and ethanol are consumed at the same time, toxic levels of the barbiturate can accumulate in the blood.', '34c98be3-f26a-42b4-9cda-68e2255d244c': '9.2 References and resources', 'a48032a6-dfbe-4e21-9004-eba417e95296': 'Lieberman M, Peet A. Figure 9.7 Clinical consequences of alcoholism. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 709. Figure 33.6 Acute effects of ethanol metabolism on lipid metabolism in the liver. 2017.', '52db8b30-a982-4fe1-a506-2eafd8f3fcac': 'Lieberman M, Peet A. Figure 9.8 Ethanol detoxification by MEOS. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 704. Figure 33.3 The reaction catalyzed by the microsomal ethanol-oxidizing system (MEOS; which includes CYP2E1) in the endoplasmic reticulum (ER). 2017. Chemical structure by Henry Jakubowski.'}"
Figure 9.7,cell_bio/images/Figure 9.7.jpg,Figure 9.7: Clinical consequences of alcoholism.,"At higher concentrations of ethanol, the microsomal ethanol oxidizing system (MEOS) becomes activated (figure 9.7; label 9). This pathway consists of a series of cytochrome P450 enzymes, which have a relatively high Km for ethanol and are located in the hepatic smooth endoplasmic reticulum (SER). This microsomal-ethanol oxidizing system also detoxifies drugs such as barbiturates (figure 9.8).","{'92209e04-09ea-4e80-8a0b-5bd3bdbd1df4': 'At higher concentrations of ethanol, the microsomal ethanol oxidizing system (MEOS) becomes activated (figure 9.7; label 9). This pathway consists of a series of cytochrome P450 enzymes, which have a relatively high Km for ethanol and are located in the hepatic smooth endoplasmic reticulum (SER). This microsomal-ethanol oxidizing system also detoxifies drugs such as barbiturates (figure 9.8).', 'eb469236-4d0a-482d-9468-5006df6d0d00': 'Although the MEOS system does not impact the NADH/NAD+ ratio, that is not to suggest that induction of this system is without metabolic consequences. Induction of the P450 system can negatively impact the metabolism of other drugs causing serious side effects. One example of this is altered metabolism of acetaminophen (Tylenol). Acetaminophen can be glucuronylated or sulfated in the liver for safe excretion by the kidney. However, the cytochrome P450 system can metabolize acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI), which requires conjugation with glutathione prior to excretion. The enzyme that produces NAPQI, CYP2E1, is induced by alcohol through the MEOS. Thus, individuals who chronically abuse alcohol have increased sensitivity to acetaminophen toxicity because a higher percentage of acetaminophen metabolism is directed toward NAPQI, compared with an individual with low levels of CYP2E1.', 'de0bd9f2-bfa0-4c90-b99b-d70ad56769a9': 'Ethanol is also an inhibitor of the phenobarbital-oxidizing P450 system. When large amounts of ethanol are consumed, the inactivation of phenobarbital is directly or indirectly inhibited. Therefore, when high doses of phenobarbital and ethanol are consumed at the same time, toxic levels of the barbiturate can accumulate in the blood.', '34c98be3-f26a-42b4-9cda-68e2255d244c': '9.2 References and resources', 'a48032a6-dfbe-4e21-9004-eba417e95296': 'Lieberman M, Peet A. Figure 9.7 Clinical consequences of alcoholism. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 709. Figure 33.6 Acute effects of ethanol metabolism on lipid metabolism in the liver. 2017.', '52db8b30-a982-4fe1-a506-2eafd8f3fcac': 'Lieberman M, Peet A. Figure 9.8 Ethanol detoxification by MEOS. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 704. Figure 33.3 The reaction catalyzed by the microsomal ethanol-oxidizing system (MEOS; which includes CYP2E1) in the endoplasmic reticulum (ER). 2017. Chemical structure by Henry Jakubowski.'}"
Figure 9.8,cell_bio/images/Figure 9.8.jpg,Figure 9.8: Ethanol detoxification by MEOS.,"Lieberman M, Peet A. Figure 9.8 Ethanol detoxification by MEOS. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 704. Figure 33.3 The reaction catalyzed by the microsomal ethanol-oxidizing system (MEOS; which includes CYP2E1) in the endoplasmic reticulum (ER). 2017. Chemical structure by Henry Jakubowski.","{'eb469236-4d0a-482d-9468-5006df6d0d00': 'Although the MEOS system does not impact the NADH/NAD+ ratio, that is not to suggest that induction of this system is without metabolic consequences. Induction of the P450 system can negatively impact the metabolism of other drugs causing serious side effects. One example of this is altered metabolism of acetaminophen (Tylenol). Acetaminophen can be glucuronylated or sulfated in the liver for safe excretion by the kidney. However, the cytochrome P450 system can metabolize acetaminophen to the toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI), which requires conjugation with glutathione prior to excretion. The enzyme that produces NAPQI, CYP2E1, is induced by alcohol through the MEOS. Thus, individuals who chronically abuse alcohol have increased sensitivity to acetaminophen toxicity because a higher percentage of acetaminophen metabolism is directed toward NAPQI, compared with an individual with low levels of CYP2E1.', 'de0bd9f2-bfa0-4c90-b99b-d70ad56769a9': 'Ethanol is also an inhibitor of the phenobarbital-oxidizing P450 system. When large amounts of ethanol are consumed, the inactivation of phenobarbital is directly or indirectly inhibited. Therefore, when high doses of phenobarbital and ethanol are consumed at the same time, toxic levels of the barbiturate can accumulate in the blood.', '34c98be3-f26a-42b4-9cda-68e2255d244c': '9.2 References and resources', 'a48032a6-dfbe-4e21-9004-eba417e95296': 'Lieberman M, Peet A. Figure 9.7 Clinical consequences of alcoholism. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 709. Figure 33.6 Acute effects of ethanol metabolism on lipid metabolism in the liver. 2017.', '52db8b30-a982-4fe1-a506-2eafd8f3fcac': 'Lieberman M, Peet A. Figure 9.8 Ethanol detoxification by MEOS. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 704. Figure 33.3 The reaction catalyzed by the microsomal ethanol-oxidizing system (MEOS; which includes CYP2E1) in the endoplasmic reticulum (ER). 2017. Chemical structure by Henry Jakubowski.'}"
Figure 8.1,cell_bio/images/Figure 8.1.jpg,Figure 8.1: Metabolism of phenylalanine requires BH4 and also produces tyrosine. Deficiencies in cofactor or phenylalanine hydroxylase can result in phenylketonuria.,"Phenylalanine is an essential amino acid, and hydroxylation of Phe by phenylalanine hydroxylase (PAH) generates tyrosine (figure 8.1). This conversion requires BH4, and deficiencies in either the cofactor or the enzyme PAH can result in phenylketonuria. Additionally, the inability to synthesize tyrosine will make this a conditionally essential amino acid and potentially negatively impact the synthesis of downstream compounds illustrated in figure 8.1.","{'16206c7e-e332-4515-81ca-14a70772cada': 'Phenylalanine is an essential amino acid, and hydroxylation of Phe by phenylalanine hydroxylase (PAH) generates tyrosine (figure 8.1). This conversion requires BH4, and deficiencies in either the cofactor or the enzyme PAH can result in phenylketonuria. Additionally, the inability to synthesize tyrosine will make this a conditionally essential amino acid and potentially negatively impact the synthesis of downstream compounds illustrated in figure 8.1.', '43093863-1864-47d6-94d7-d1ff1fa7ad23': 'Tyrosine can be produced from phenylalanine metabolism and is required for the production of melanin and the catecholamines. Deficiencies can occur at several different locations in the pathway and result in albinism (tyrosinase), alkaptonuria (homogentisate oxidase), or tyrosinemia, which can manifest due to deficiencies in several enzymes along the pathway (figure 8.2).', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.2,cell_bio/images/Figure 8.2.jpg,"Figure 8.2: Tyrosine can be produced from phenylalanine metabolism and is required for the production of melanin and the catecholamines. Deficiencies can occur at several different locations in the pathway and result in albinism, alkaptonuria, or tyrosinemia.","Tyrosine can be produced from phenylalanine metabolism and is required for the production of melanin and the catecholamines. Deficiencies can occur at several different locations in the pathway and result in albinism (tyrosinase), alkaptonuria (homogentisate oxidase), or tyrosinemia, which can manifest due to deficiencies in several enzymes along the pathway (figure 8.2).","{'16206c7e-e332-4515-81ca-14a70772cada': 'Phenylalanine is an essential amino acid, and hydroxylation of Phe by phenylalanine hydroxylase (PAH) generates tyrosine (figure 8.1). This conversion requires BH4, and deficiencies in either the cofactor or the enzyme PAH can result in phenylketonuria. Additionally, the inability to synthesize tyrosine will make this a conditionally essential amino acid and potentially negatively impact the synthesis of downstream compounds illustrated in figure 8.1.', '43093863-1864-47d6-94d7-d1ff1fa7ad23': 'Tyrosine can be produced from phenylalanine metabolism and is required for the production of melanin and the catecholamines. Deficiencies can occur at several different locations in the pathway and result in albinism (tyrosinase), alkaptonuria (homogentisate oxidase), or tyrosinemia, which can manifest due to deficiencies in several enzymes along the pathway (figure 8.2).', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.3,cell_bio/images/Figure 8.3.jpg,Figure 8.3: Metabolism of tryptophan to melatonin.,"Tryptophan is an essential amino acid that is both ketogenic and glucogenic as it can be oxidized to produce alanine and acetyl-CoA. The ring structure can also be used to synthesize niacin, reducing the dietary requirement for this vitamin. Tryptophan metabolism to serotonin (and subsequently melatonin) requires BH4. Deficiencies here can lead to imbalances in these neurotransmitters (figure 8.3).","{'1c7f1105-3b0b-4c96-903c-9ef6c3de37b7': 'Tryptophan is an essential amino acid that is both ketogenic and glucogenic as it can be oxidized to produce alanine and acetyl-CoA. The ring structure can also be used to synthesize niacin, reducing the dietary requirement for this vitamin. Tryptophan metabolism to serotonin (and subsequently melatonin) requires BH4. Deficiencies here can lead to imbalances in these neurotransmitters (figure 8.3).', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.4,cell_bio/images/Figure 8.4.jpg,Figure 8.4: Glutamate metabolism as it interfaces with nitrogen transport and synthesis of GABA.,"Glutamate plays many key roles in amino acid metabolism and provides substrates for GABA and glutathione synthesis (figure 8.4). Additionally, glutamate plays a key role in nitrogen movement within the body. Glutamate can be deaminated by glutamate dehydrogenase to yield α-ketoglutarate. This can enter directly into the TCA cycle or be transaminated (figure 8.4). Additionally, glutamate can be used to fix or free ammonium to generate glutamine — one of the essential, nontoxic carriers of ammonia.","{'26ab8bb4-1aad-411d-b66d-b7bea7aa8540': 'Glutamate plays many key roles in amino acid metabolism and provides substrates for GABA and glutathione synthesis (figure 8.4). Additionally, glutamate plays a key role in nitrogen movement within the body. Glutamate can be deaminated by glutamate dehydrogenase to yield α-ketoglutarate. This can enter directly into the TCA cycle or be transaminated (figure 8.4). Additionally, glutamate can be used to fix or free ammonium to generate glutamine — one of the essential, nontoxic carriers of ammonia.', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.6,cell_bio/images/Figure 8.6.jpg,Figure 8.6: Metabolism of methionine. Remethylation and transsulfuration of homocysteine are illustrated. Cofactor or enzymatic deficiencies can result in an elevation of homocysteine.,"Homocysteine, generated from this reaction, can either be remethylated in a reaction using both folate and cobalamin to resynthesize methionine or can be used for the synthesis or cysteine (figure 8.6).","{'f3b6b42d-cf76-4c17-b9bb-8bfa473d604e': 'Methionine is an essential amino acid with a complex metabolism of clinical importance. Its metabolism interfaces with the folate cycle, cobalamin remethylation, and the synthesis of S-adenosylmethionine (SAM). Enzymatic or cofactor deficiencies can result in elevated homocysteine levels (hyperhomocysteinemia), which can have negative impacts systemically. Methionine, required for the synthesis of SAM, can be obtained from the diet or produced from remethylation of homocysteine using vitamin B12.', 'e75abb8e-395e-4c05-9fe3-b37bcb557218': 'Initially, methionine will condense with ATP to form SAM. SAM has a charged methyl group, which can be transferred to many different acceptor molecules; this step is considered irreversible as the amount of energy released is substantial. SAM is used by many biological pathways to donate methyl groups, and it is in consistent demand. After SAM loses its methyl group, the resulting compound, S-adenosylhomocysteine (SAH), is hydrolyzed to homocysteine and adenosine.', '26763c6d-276a-41c0-b71a-fef1c15936c8': 'Homocysteine, generated from this reaction, can either be remethylated in a reaction using both folate and cobalamin to resynthesize methionine or can be used for the synthesis or cysteine (figure 8.6).', '05b21266-126e-48b3-97a5-fc4e536bac6d': 'Further metabolism of homocysteine provides the sulfur atom for the synthesis of cysteine. In this two-step process, homocysteine first reacts with serine to form cystathionine. This is followed by cleavage of cystathionine, which yields cysteine and α-ketobutyrate. The first reaction in this sequence, catalyzed by cystathionine β-synthase, is inhibited by cysteine. Thus, methionine, via homocysteine, is not used for cysteine synthesis unless the levels of cysteine in the body are lower than required for its metabolic functions. An adequate dietary supply of cysteine, therefore, can “spare” (or reduce) the dietary requirement for methionine (figure 8.6).', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.6,cell_bio/images/Figure 8.6.jpg,Figure 8.6: Metabolism of methionine. Remethylation and transsulfuration of homocysteine are illustrated. Cofactor or enzymatic deficiencies can result in an elevation of homocysteine.,"Homocysteine, generated from this reaction, can either be remethylated in a reaction using both folate and cobalamin to resynthesize methionine or can be used for the synthesis or cysteine (figure 8.6).","{'f3b6b42d-cf76-4c17-b9bb-8bfa473d604e': 'Methionine is an essential amino acid with a complex metabolism of clinical importance. Its metabolism interfaces with the folate cycle, cobalamin remethylation, and the synthesis of S-adenosylmethionine (SAM). Enzymatic or cofactor deficiencies can result in elevated homocysteine levels (hyperhomocysteinemia), which can have negative impacts systemically. Methionine, required for the synthesis of SAM, can be obtained from the diet or produced from remethylation of homocysteine using vitamin B12.', 'e75abb8e-395e-4c05-9fe3-b37bcb557218': 'Initially, methionine will condense with ATP to form SAM. SAM has a charged methyl group, which can be transferred to many different acceptor molecules; this step is considered irreversible as the amount of energy released is substantial. SAM is used by many biological pathways to donate methyl groups, and it is in consistent demand. After SAM loses its methyl group, the resulting compound, S-adenosylhomocysteine (SAH), is hydrolyzed to homocysteine and adenosine.', '26763c6d-276a-41c0-b71a-fef1c15936c8': 'Homocysteine, generated from this reaction, can either be remethylated in a reaction using both folate and cobalamin to resynthesize methionine or can be used for the synthesis or cysteine (figure 8.6).', '05b21266-126e-48b3-97a5-fc4e536bac6d': 'Further metabolism of homocysteine provides the sulfur atom for the synthesis of cysteine. In this two-step process, homocysteine first reacts with serine to form cystathionine. This is followed by cleavage of cystathionine, which yields cysteine and α-ketobutyrate. The first reaction in this sequence, catalyzed by cystathionine β-synthase, is inhibited by cysteine. Thus, methionine, via homocysteine, is not used for cysteine synthesis unless the levels of cysteine in the body are lower than required for its metabolic functions. An adequate dietary supply of cysteine, therefore, can “spare” (or reduce) the dietary requirement for methionine (figure 8.6).', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.1,cell_bio/images/Figure 8.1.jpg,Figure 8.1: Metabolism of phenylalanine requires BH4 and also produces tyrosine. Deficiencies in cofactor or phenylalanine hydroxylase can result in phenylketonuria.,"Phenylalanine is an essential amino acid, and hydroxylation of Phe by phenylalanine hydroxylase (PAH) generates tyrosine (figure 8.1). This conversion requires BH4, and deficiencies in either the cofactor or the enzyme PAH can result in phenylketonuria. Additionally, the inability to synthesize tyrosine will make this a conditionally essential amino acid and potentially negatively impact the synthesis of downstream compounds illustrated in figure 8.1.","{'16206c7e-e332-4515-81ca-14a70772cada': 'Phenylalanine is an essential amino acid, and hydroxylation of Phe by phenylalanine hydroxylase (PAH) generates tyrosine (figure 8.1). This conversion requires BH4, and deficiencies in either the cofactor or the enzyme PAH can result in phenylketonuria. Additionally, the inability to synthesize tyrosine will make this a conditionally essential amino acid and potentially negatively impact the synthesis of downstream compounds illustrated in figure 8.1.', '43093863-1864-47d6-94d7-d1ff1fa7ad23': 'Tyrosine can be produced from phenylalanine metabolism and is required for the production of melanin and the catecholamines. Deficiencies can occur at several different locations in the pathway and result in albinism (tyrosinase), alkaptonuria (homogentisate oxidase), or tyrosinemia, which can manifest due to deficiencies in several enzymes along the pathway (figure 8.2).', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.2,cell_bio/images/Figure 8.2.jpg,"Figure 8.2: Tyrosine can be produced from phenylalanine metabolism and is required for the production of melanin and the catecholamines. Deficiencies can occur at several different locations in the pathway and result in albinism, alkaptonuria, or tyrosinemia.","Tyrosine can be produced from phenylalanine metabolism and is required for the production of melanin and the catecholamines. Deficiencies can occur at several different locations in the pathway and result in albinism (tyrosinase), alkaptonuria (homogentisate oxidase), or tyrosinemia, which can manifest due to deficiencies in several enzymes along the pathway (figure 8.2).","{'16206c7e-e332-4515-81ca-14a70772cada': 'Phenylalanine is an essential amino acid, and hydroxylation of Phe by phenylalanine hydroxylase (PAH) generates tyrosine (figure 8.1). This conversion requires BH4, and deficiencies in either the cofactor or the enzyme PAH can result in phenylketonuria. Additionally, the inability to synthesize tyrosine will make this a conditionally essential amino acid and potentially negatively impact the synthesis of downstream compounds illustrated in figure 8.1.', '43093863-1864-47d6-94d7-d1ff1fa7ad23': 'Tyrosine can be produced from phenylalanine metabolism and is required for the production of melanin and the catecholamines. Deficiencies can occur at several different locations in the pathway and result in albinism (tyrosinase), alkaptonuria (homogentisate oxidase), or tyrosinemia, which can manifest due to deficiencies in several enzymes along the pathway (figure 8.2).', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.3,cell_bio/images/Figure 8.3.jpg,Figure 8.3: Metabolism of tryptophan to melatonin.,"Tryptophan is an essential amino acid that is both ketogenic and glucogenic as it can be oxidized to produce alanine and acetyl-CoA. The ring structure can also be used to synthesize niacin, reducing the dietary requirement for this vitamin. Tryptophan metabolism to serotonin (and subsequently melatonin) requires BH4. Deficiencies here can lead to imbalances in these neurotransmitters (figure 8.3).","{'1c7f1105-3b0b-4c96-903c-9ef6c3de37b7': 'Tryptophan is an essential amino acid that is both ketogenic and glucogenic as it can be oxidized to produce alanine and acetyl-CoA. The ring structure can also be used to synthesize niacin, reducing the dietary requirement for this vitamin. Tryptophan metabolism to serotonin (and subsequently melatonin) requires BH4. Deficiencies here can lead to imbalances in these neurotransmitters (figure 8.3).', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.4,cell_bio/images/Figure 8.4.jpg,Figure 8.4: Glutamate metabolism as it interfaces with nitrogen transport and synthesis of GABA.,"Glutamate plays many key roles in amino acid metabolism and provides substrates for GABA and glutathione synthesis (figure 8.4). Additionally, glutamate plays a key role in nitrogen movement within the body. Glutamate can be deaminated by glutamate dehydrogenase to yield α-ketoglutarate. This can enter directly into the TCA cycle or be transaminated (figure 8.4). Additionally, glutamate can be used to fix or free ammonium to generate glutamine — one of the essential, nontoxic carriers of ammonia.","{'26ab8bb4-1aad-411d-b66d-b7bea7aa8540': 'Glutamate plays many key roles in amino acid metabolism and provides substrates for GABA and glutathione synthesis (figure 8.4). Additionally, glutamate plays a key role in nitrogen movement within the body. Glutamate can be deaminated by glutamate dehydrogenase to yield α-ketoglutarate. This can enter directly into the TCA cycle or be transaminated (figure 8.4). Additionally, glutamate can be used to fix or free ammonium to generate glutamine — one of the essential, nontoxic carriers of ammonia.', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.5,cell_bio/images/Figure 8.5.jpg,,Figure 8.5: Metabolism of branched-chain amino acids. Deficiencies in branched-chain keto acid dehydrogenase (BCKAD) can result in the presentation of maple syrup urine disease.,"{'13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 8.6,cell_bio/images/Figure 8.6.jpg,Figure 8.6: Metabolism of methionine. Remethylation and transsulfuration of homocysteine are illustrated. Cofactor or enzymatic deficiencies can result in an elevation of homocysteine.,"Homocysteine, generated from this reaction, can either be remethylated in a reaction using both folate and cobalamin to resynthesize methionine or can be used for the synthesis or cysteine (figure 8.6).","{'f3b6b42d-cf76-4c17-b9bb-8bfa473d604e': 'Methionine is an essential amino acid with a complex metabolism of clinical importance. Its metabolism interfaces with the folate cycle, cobalamin remethylation, and the synthesis of S-adenosylmethionine (SAM). Enzymatic or cofactor deficiencies can result in elevated homocysteine levels (hyperhomocysteinemia), which can have negative impacts systemically. Methionine, required for the synthesis of SAM, can be obtained from the diet or produced from remethylation of homocysteine using vitamin B12.', 'e75abb8e-395e-4c05-9fe3-b37bcb557218': 'Initially, methionine will condense with ATP to form SAM. SAM has a charged methyl group, which can be transferred to many different acceptor molecules; this step is considered irreversible as the amount of energy released is substantial. SAM is used by many biological pathways to donate methyl groups, and it is in consistent demand. After SAM loses its methyl group, the resulting compound, S-adenosylhomocysteine (SAH), is hydrolyzed to homocysteine and adenosine.', '26763c6d-276a-41c0-b71a-fef1c15936c8': 'Homocysteine, generated from this reaction, can either be remethylated in a reaction using both folate and cobalamin to resynthesize methionine or can be used for the synthesis or cysteine (figure 8.6).', '05b21266-126e-48b3-97a5-fc4e536bac6d': 'Further metabolism of homocysteine provides the sulfur atom for the synthesis of cysteine. In this two-step process, homocysteine first reacts with serine to form cystathionine. This is followed by cleavage of cystathionine, which yields cysteine and α-ketobutyrate. The first reaction in this sequence, catalyzed by cystathionine β-synthase, is inhibited by cysteine. Thus, methionine, via homocysteine, is not used for cysteine synthesis unless the levels of cysteine in the body are lower than required for its metabolic functions. An adequate dietary supply of cysteine, therefore, can “spare” (or reduce) the dietary requirement for methionine (figure 8.6).', '13d69ff5-a9fb-4f18-8367-db1ea1640c20': 'Homocysteine levels can accumulate in several ways, which are related to both folic acid and vitamin B12 metabolism. As SAM is constantly being used as a methyl donor, this results in a consistent production of SAH. Consequently, this leads to constant production of homocysteine. The homocysteine produced can be either remethylated to methionine or condensed with serine to form cystathionine. The major pathway of homocysteine metabolism is remethylation by N5-methyl-FH4, which requires vitamin B12. The liver also contains a second pathway in which betaine (a degradation product of choline) can donate a methyl group to homocysteine to form methionine, but this is a minor pathway. The conversion of homocysteine to cystathionine requires pyridoxal phosphate (PLP). Thus, if an individual is deficient in vitamin B12, the conversion of homocysteine to methionine by the major route is inhibited. This directs homocysteine to produce cystathionine, which eventually produces cysteine. Homocysteine also accumulates in the blood if a mutation is present in the enzyme that converts N5,N10-methylene-FH4 to N5-methyl-FH4. When this occurs, the levels of N5-methyl-FH4 are too low to allow homocysteine to be converted to methionine. The loss of this pathway, coupled with the feedback inhibition by cysteine on cystathionine formation, also leads to elevated homocysteine levels in the blood. A third way in which serum homocysteine levels can be elevated is by a mutated cystathionine β-synthase or a deficiency in vitamin B6, the required cofactor for that enzyme. These defects block the ability of homocysteine to be converted to cystathionine, and the homocysteine that does accumulate cannot all be accommodated by conversion to methionine. Thus, an accumulation of homocysteine results.', '8ced2fa3-988f-45e1-87fc-4dc0c1d395aa': '8.1 References and resources', '9073a959-4469-4452-9fdc-ce3b70fb8e8e': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 20: Amino Acid Degradation and Synthesis, Chapter 21: Conversion of Amino Acids to Specialized Products.', 'c209815b-2793-44c0-9162-1a58319726ef': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 69, 83–85.', 'a1f1ddd4-cc27-483c-b67c-4f21685c54e1': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 37: Synthesis and Degradation of Amino Acids, Chapter 39: Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine.'}"
Figure 7.1,cell_bio/images/Figure 7.1.jpg,Figure 7.1: Overview of the pentose phosphate pathway and its interface with glycolysis.,"The nonoxidative phase of the pathway allows for the conversion of ribulose 5-phosphate into ribose 5-phosphate, which is needed for nucleotide synthesis (figure 7.1). All of these interconversions in the nonoxidative pathway are reversible and use the enzymes transketolase or transaldolase to move two-carbon or three-carbon units on to other sugar moieties to generate a variety of sugar intermediates. Transketolase requires thiamine pyrophosphate (TPP) as a cofactor. This is of clinical relevance as TPP levels can be measured by addressing the activity of transketolase in a blood sample. A reduction in transketolase activity is an indicator of a thiamine deficiency.","{'b0e54d27-17fc-4590-956c-ad9c1593e234': 'There are two parts of the pathway that\xa0are distinct and can be regulated independently. The first phase, or oxidative phase, consists of two irreversible oxidations that produce NADPH. As noted above, NADPH is required for reductive detoxification and fatty acid synthesis. (NADPH is not oxidized in the ETC.) In the red blood cell, this is extremely important as the PPP pathway provides the only source of NADPH. NADPH is essential to maintain sufficient levels of reduced glutathione in the red blood cell. Glutathione is a tripeptide commonly used in tissues to detoxify free radicals and reduce cellular oxidation.', '892e0996-4fc2-4d34-8935-7b4af306730f': 'The nonoxidative phase of the pathway allows for the conversion of ribulose 5-phosphate into ribose 5-phosphate, which is needed for nucleotide synthesis (figure 7.1). All of these interconversions in the nonoxidative pathway are reversible and use the enzymes transketolase or transaldolase to move two-carbon or three-carbon units on to other sugar moieties to generate a variety of sugar intermediates. Transketolase requires thiamine pyrophosphate (TPP) as a cofactor. This is of clinical relevance as TPP levels can be measured by addressing the activity of transketolase in a blood sample. A reduction in transketolase activity is an indicator of a thiamine deficiency.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 7.2,cell_bio/images/Figure 7.2.jpg,Figure 7.2: Pentose phosphate pathway and its connection to glycolysis and glutathione synthesis.,"The nonoxidative phase is not regulated; however, in conditions where there is a high demand for nucleotide production (such as in the case for highly proliferative cells), the nonoxidative part of the pathway can function independently of the oxidative phase to produce ribose 5-phosphate from the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate (figure 7.2).","{'f9ca581e-2fc4-4113-bd70-bbd80939deeb': 'The key regulatory enzyme for the pentose phosphate pathway is within\xa0the oxidative portion. Glucose 6-phosphate dehydrogenase oxidizes glucose 6-phosphate to 6-phosphogluconolactone, and is regulated by negative feedback. In this two-step reaction NADPH is also produced, and high levels of NADPH will inhibit the activity of glucose 6-phosphate dehydrogenase. This ensures NADPH is only generated as needed by the cell; this is the primary regulatory mechanism within the pathway.', '00b1d987-90dc-41f9-aa60-3fe9fc7b90cc': 'The nonoxidative phase is not regulated; however, in conditions where there is a high demand for nucleotide production (such as in the case for highly proliferative cells), the nonoxidative part of the pathway can function independently of the oxidative phase to produce ribose 5-phosphate from the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate (figure 7.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 7.3,cell_bio/images/Figure 7.3.jpg,Figure 7.3: NADPH in the red blood cell as a means of reducing glutathione.,"The two essential products of this pathway are NADPH and ribose 5-phosphate. NADPH is a high-energy compound often used for reductive biosynthesis as it cannot be oxidized in the ETC. It is also used by many tissues to scavenge (and detoxify) reactive oxygen species (ROS) before causing cellular damage. This is especially important in red blood cells; RBCs lack malic enzyme, making this the only pathway that can generate NADPH. A lack of NADPH in RBCs (such as due to a glucose 6-phosphate dehydrogenase deficiency) can cause excessive hemolysis, leading to the clinical presentation of jaundice (figure 7.3).","{'d4a8e0d7-14de-4ec0-9e57-490a8cfb7b45': 'The two essential products of this pathway are NADPH and ribose 5-phosphate. NADPH is a high-energy compound often used for reductive biosynthesis as it cannot be oxidized in the ETC. It is also used by many tissues to scavenge (and detoxify) reactive oxygen species (ROS) before causing cellular damage. This is especially important in red blood cells; RBCs lack malic enzyme, making this the only pathway that can generate NADPH. A lack of NADPH in RBCs (such as due to a glucose 6-phosphate dehydrogenase deficiency) can cause excessive hemolysis, leading to the clinical presentation of jaundice (figure 7.3).', '88776739-a963-4fcf-8f3a-95d57868500d': 'Glutathione (GSH) is a tripeptide compound consisting of glutamate, cysteine, and glycine. It plays a key role\xa0in scavenging reactive oxygen species (ROS), which cause both DNA and cellular/protein damage. Reduction of GSH in the red blood cell is done exclusively through a series of oxidation reduction reactions using NADPH. The loss of NADPH in RBCs therefore increases ROS and can lead to hemolysis (figure 7.3).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 7.3,cell_bio/images/Figure 7.3.jpg,Figure 7.3: NADPH in the red blood cell as a means of reducing glutathione.,"The two essential products of this pathway are NADPH and ribose 5-phosphate. NADPH is a high-energy compound often used for reductive biosynthesis as it cannot be oxidized in the ETC. It is also used by many tissues to scavenge (and detoxify) reactive oxygen species (ROS) before causing cellular damage. This is especially important in red blood cells; RBCs lack malic enzyme, making this the only pathway that can generate NADPH. A lack of NADPH in RBCs (such as due to a glucose 6-phosphate dehydrogenase deficiency) can cause excessive hemolysis, leading to the clinical presentation of jaundice (figure 7.3).","{'d4a8e0d7-14de-4ec0-9e57-490a8cfb7b45': 'The two essential products of this pathway are NADPH and ribose 5-phosphate. NADPH is a high-energy compound often used for reductive biosynthesis as it cannot be oxidized in the ETC. It is also used by many tissues to scavenge (and detoxify) reactive oxygen species (ROS) before causing cellular damage. This is especially important in red blood cells; RBCs lack malic enzyme, making this the only pathway that can generate NADPH. A lack of NADPH in RBCs (such as due to a glucose 6-phosphate dehydrogenase deficiency) can cause excessive hemolysis, leading to the clinical presentation of jaundice (figure 7.3).', '88776739-a963-4fcf-8f3a-95d57868500d': 'Glutathione (GSH) is a tripeptide compound consisting of glutamate, cysteine, and glycine. It plays a key role\xa0in scavenging reactive oxygen species (ROS), which cause both DNA and cellular/protein damage. Reduction of GSH in the red blood cell is done exclusively through a series of oxidation reduction reactions using NADPH. The loss of NADPH in RBCs therefore increases ROS and can lead to hemolysis (figure 7.3).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 7.2,cell_bio/images/Figure 7.2.jpg,Figure 7.2: Pentose phosphate pathway and its connection to glycolysis and glutathione synthesis.,"The nonoxidative phase is not regulated; however, in conditions where there is a high demand for nucleotide production (such as in the case for highly proliferative cells), the nonoxidative part of the pathway can function independently of the oxidative phase to produce ribose 5-phosphate from the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate (figure 7.2).","{'f9ca581e-2fc4-4113-bd70-bbd80939deeb': 'The key regulatory enzyme for the pentose phosphate pathway is within\xa0the oxidative portion. Glucose 6-phosphate dehydrogenase oxidizes glucose 6-phosphate to 6-phosphogluconolactone, and is regulated by negative feedback. In this two-step reaction NADPH is also produced, and high levels of NADPH will inhibit the activity of glucose 6-phosphate dehydrogenase. This ensures NADPH is only generated as needed by the cell; this is the primary regulatory mechanism within the pathway.', '00b1d987-90dc-41f9-aa60-3fe9fc7b90cc': 'The nonoxidative phase is not regulated; however, in conditions where there is a high demand for nucleotide production (such as in the case for highly proliferative cells), the nonoxidative part of the pathway can function independently of the oxidative phase to produce ribose 5-phosphate from the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate (figure 7.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 7.1,cell_bio/images/Figure 7.1.jpg,Figure 7.1: Overview of the pentose phosphate pathway and its interface with glycolysis.,"The nonoxidative phase of the pathway allows for the conversion of ribulose 5-phosphate into ribose 5-phosphate, which is needed for nucleotide synthesis (figure 7.1). All of these interconversions in the nonoxidative pathway are reversible and use the enzymes transketolase or transaldolase to move two-carbon or three-carbon units on to other sugar moieties to generate a variety of sugar intermediates. Transketolase requires thiamine pyrophosphate (TPP) as a cofactor. This is of clinical relevance as TPP levels can be measured by addressing the activity of transketolase in a blood sample. A reduction in transketolase activity is an indicator of a thiamine deficiency.","{'b0e54d27-17fc-4590-956c-ad9c1593e234': 'There are two parts of the pathway that\xa0are distinct and can be regulated independently. The first phase, or oxidative phase, consists of two irreversible oxidations that produce NADPH. As noted above, NADPH is required for reductive detoxification and fatty acid synthesis. (NADPH is not oxidized in the ETC.) In the red blood cell, this is extremely important as the PPP pathway provides the only source of NADPH. NADPH is essential to maintain sufficient levels of reduced glutathione in the red blood cell. Glutathione is a tripeptide commonly used in tissues to detoxify free radicals and reduce cellular oxidation.', '892e0996-4fc2-4d34-8935-7b4af306730f': 'The nonoxidative phase of the pathway allows for the conversion of ribulose 5-phosphate into ribose 5-phosphate, which is needed for nucleotide synthesis (figure 7.1). All of these interconversions in the nonoxidative pathway are reversible and use the enzymes transketolase or transaldolase to move two-carbon or three-carbon units on to other sugar moieties to generate a variety of sugar intermediates. Transketolase requires thiamine pyrophosphate (TPP) as a cofactor. This is of clinical relevance as TPP levels can be measured by addressing the activity of transketolase in a blood sample. A reduction in transketolase activity is an indicator of a thiamine deficiency.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 7.3,cell_bio/images/Figure 7.3.jpg,Figure 7.3: NADPH in the red blood cell as a means of reducing glutathione.,"The two essential products of this pathway are NADPH and ribose 5-phosphate. NADPH is a high-energy compound often used for reductive biosynthesis as it cannot be oxidized in the ETC. It is also used by many tissues to scavenge (and detoxify) reactive oxygen species (ROS) before causing cellular damage. This is especially important in red blood cells; RBCs lack malic enzyme, making this the only pathway that can generate NADPH. A lack of NADPH in RBCs (such as due to a glucose 6-phosphate dehydrogenase deficiency) can cause excessive hemolysis, leading to the clinical presentation of jaundice (figure 7.3).","{'d4a8e0d7-14de-4ec0-9e57-490a8cfb7b45': 'The two essential products of this pathway are NADPH and ribose 5-phosphate. NADPH is a high-energy compound often used for reductive biosynthesis as it cannot be oxidized in the ETC. It is also used by many tissues to scavenge (and detoxify) reactive oxygen species (ROS) before causing cellular damage. This is especially important in red blood cells; RBCs lack malic enzyme, making this the only pathway that can generate NADPH. A lack of NADPH in RBCs (such as due to a glucose 6-phosphate dehydrogenase deficiency) can cause excessive hemolysis, leading to the clinical presentation of jaundice (figure 7.3).', '88776739-a963-4fcf-8f3a-95d57868500d': 'Glutathione (GSH) is a tripeptide compound consisting of glutamate, cysteine, and glycine. It plays a key role\xa0in scavenging reactive oxygen species (ROS), which cause both DNA and cellular/protein damage. Reduction of GSH in the red blood cell is done exclusively through a series of oxidation reduction reactions using NADPH. The loss of NADPH in RBCs therefore increases ROS and can lead to hemolysis (figure 7.3).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 7.4,cell_bio/images/Figure 7.4.jpg,Figure 7.4: Basic structure of nucleotides.,"Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three functional groups: a sugar, a base, and phosphate (figure 7.4).","{'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.5,cell_bio/images/Figure 7.5.jpg,Figure 7.5: Overview of purine and pyrimidine bases.,"Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).","{'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.6,cell_bio/images/Figure 7.6.jpg,Figure 7.6: Synthesis of PRPP and regulation of PRPP synthetase.,"Ribose 5-phosphate is not used directly for either purine or pyrimidine synthesis, rather it is used to synthesize the “active pentose” — 5-phosphoribosyl-1-pyrophosphate (PRPP). The conversion is catalyzed by the enzyme phosphoribosyl-1-pyrophosphate (PRPP) synthase. PRPP is the activated five-carbon sugar used for nucleotide synthesis and provides both the sugar and phosphate group to nucleotides (figure 7.6).","{'b6aca37f-cfe6-4c57-a4dc-a48830ec8132': 'Ribose 5-phosphate is not used directly for either purine or pyrimidine synthesis, rather it is used to synthesize the “active pentose”\xa0—\xa05-phosphoribosyl-1-pyrophosphate (PRPP). The conversion is catalyzed by the enzyme phosphoribosyl-1-pyrophosphate (PRPP) synthase. PRPP is the activated five-carbon sugar used for nucleotide synthesis and provides both the sugar and phosphate group to nucleotides (figure 7.6).', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.7,cell_bio/images/Figure 7.7.jpg,Figure 7.7: Overview of purine synthesis. The reaction catalyzed by GPAT is the regulatory enzyme of the pathway.,"Purines are composed of a bicyclic structure that is synthesized from carbon and nitrogen donated from various compounds such as carbon dioxide, glycine, glutamine, aspartate, and tetrahydrofolate (TH4). The synthesis of purines starts with the synthesis of 5ʼphosphoribosylamine from PRPP and glutamine. The enzyme glutamine phosphoribosylpyrophate amidotransferase (GPAT) catalyzes this reaction and is the committed step in purine synthesis (figure 7.7). Synthesis continues for nine additional steps culminating in the synthesis of inosine monophosphate (IMP), which contains the base hypoxanthine. IMP is used to generate both AMP and GMP. The synthesis of both AMP and GMP requires energy in the form of the alternative base (i.e., the synthesis of GMP requires ATP while AMP synthesis requires energy in the form of GTP). The synthesis of AMP and GMP is regulated by feedback inhibition (figures 7.7 and 7.8). This allows for the maintenance of nucleotides in a relative ratio that is required for cellular processes. The generated nucleotide monophosphates can be converted to the di and triphosphate forms by nucleotide specific kinases, which will transfer phosphate groups to maintain a balance of the mono, di, and triphosphate forms.","{'6f5295f5-80c1-47c5-aa93-d8867fe62de9': 'Purines are composed of a bicyclic structure that is synthesized from carbon and nitrogen donated from various compounds such as\xa0carbon dioxide, glycine, glutamine, aspartate, and tetrahydrofolate (TH4). The synthesis of purines starts with the synthesis of 5ʼphosphoribosylamine from PRPP and glutamine. The enzyme glutamine phosphoribosylpyrophate amidotransferase (GPAT) catalyzes this reaction and is the committed step in purine synthesis (figure 7.7). Synthesis continues for nine\xa0additional steps culminating in the synthesis of inosine monophosphate (IMP), which contains the base hypoxanthine. IMP is used to generate both AMP and GMP. The synthesis of both AMP and GMP requires energy in the form of the alternative base\xa0(i.e., the synthesis of GMP requires ATP while AMP synthesis requires energy in the form of GTP). The synthesis of AMP and GMP is regulated by feedback inhibition (figures 7.7 and 7.8). This allows for the maintenance of nucleotides in a relative ratio that is required for cellular processes. The generated nucleotide monophosphates can be converted to the di and triphosphate forms by nucleotide specific kinases, which will transfer phosphate groups to maintain a balance of the mono, di,\xa0and triphosphate forms.', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.9,cell_bio/images/Figure 7.9.jpg,Figure 7.9: Breakdown of nucleotides.,"Degradation of dietary nucleotides occurs in the gut, while nucleotides from de novo synthesis are degraded in the liver. The fundamental process involves the dismantling of the sugar, phosphate, and base structure into their own respective units (figure 7.9). In the case of purine degradation, the base is excreted in the form of uric acid. Purine nucleoside phosphorylase converts inosine and guanosine to their respective bases (hypoxanthine and guanine). Finally, xanthine oxidase will oxidize hypoxanthine to xanthine (guanine can be deaminated to xanthine), and xanthine can be further oxidized to uric acid by the same enzyme. Uric acid is excreted in the urine.","{'2db2e660-1c37-4f4e-8ce1-fa92f6b103c6': 'Like amino acids, nucleotides contain nitrogen and must be degraded in a manner that allows for proper nitrogen disposal either through the urea cycle or by the synthesis of a nontoxic compound.', 'a81e5c48-c7b2-4ee4-9473-92a693b3e62c': 'Degradation of dietary nucleotides occurs in the gut, while nucleotides from de novo synthesis are degraded in the liver. The fundamental process involves the dismantling of the sugar, phosphate, and base structure into their own respective units (figure 7.9). In the case of purine degradation, the base is excreted in the form of uric acid. Purine nucleoside phosphorylase converts inosine and guanosine to their respective bases (hypoxanthine and guanine). Finally, xanthine oxidase will oxidize hypoxanthine to xanthine (guanine can be deaminated to xanthine), and xanthine can be further oxidized to uric acid by the same enzyme. Uric acid is excreted in the urine.', '2d94c725-7aa2-4f84-a09a-e818f8530169': 'Excess uric acid, hyperuricemia, can cause the precipitation of uric acid crystals in the joints eliciting an inflammatory reaction causing acute pain or gout. The majority of individuals diagnosed with gout present due to underexcretion of uric acid. And this can be caused by the presence of other pathologies, such as lactic acidosis\xa0or the use of diuretics. Less common presentations of gout are associated with overproduction of uric acid, which can be caused by increased activity of PRPP synthetase or deficiency in purine recycling enzyme HGPRT caused by Lesch-Nyhan syndrome (figure 7.10).', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.10,cell_bio/images/Figure 7.10.jpg,Figure 7.10: Nucleotide base salvage. Reaction catalyzed by HGPRT is clinically relevant as deficiencies can cause accumulation of uric acid.,"Excess uric acid, hyperuricemia, can cause the precipitation of uric acid crystals in the joints eliciting an inflammatory reaction causing acute pain or gout. The majority of individuals diagnosed with gout present due to underexcretion of uric acid. And this can be caused by the presence of other pathologies, such as lactic acidosis or the use of diuretics. Less common presentations of gout are associated with overproduction of uric acid, which can be caused by increased activity of PRPP synthetase or deficiency in purine recycling enzyme HGPRT caused by Lesch-Nyhan syndrome (figure 7.10).","{'2db2e660-1c37-4f4e-8ce1-fa92f6b103c6': 'Like amino acids, nucleotides contain nitrogen and must be degraded in a manner that allows for proper nitrogen disposal either through the urea cycle or by the synthesis of a nontoxic compound.', 'a81e5c48-c7b2-4ee4-9473-92a693b3e62c': 'Degradation of dietary nucleotides occurs in the gut, while nucleotides from de novo synthesis are degraded in the liver. The fundamental process involves the dismantling of the sugar, phosphate, and base structure into their own respective units (figure 7.9). In the case of purine degradation, the base is excreted in the form of uric acid. Purine nucleoside phosphorylase converts inosine and guanosine to their respective bases (hypoxanthine and guanine). Finally, xanthine oxidase will oxidize hypoxanthine to xanthine (guanine can be deaminated to xanthine), and xanthine can be further oxidized to uric acid by the same enzyme. Uric acid is excreted in the urine.', '2d94c725-7aa2-4f84-a09a-e818f8530169': 'Excess uric acid, hyperuricemia, can cause the precipitation of uric acid crystals in the joints eliciting an inflammatory reaction causing acute pain or gout. The majority of individuals diagnosed with gout present due to underexcretion of uric acid. And this can be caused by the presence of other pathologies, such as lactic acidosis\xa0or the use of diuretics. Less common presentations of gout are associated with overproduction of uric acid, which can be caused by increased activity of PRPP synthetase or deficiency in purine recycling enzyme HGPRT caused by Lesch-Nyhan syndrome (figure 7.10).', '39664de6-7ecf-4a24-96f5-a92f6809b6e3': 'The ability to recycle nucleotides is specifically important in the case of purines as de novo synthesis uses much more ATP than salvage. The degradation product of purine bases is uric acid, which is an insoluble compound, and accumulation can result in several clinical disorders as previously discussed. As such, purine bases can also undergo salvage reaction where bases are recycled and used in a new process. To reduce the\xa0amount of uric acid production, purines can be salvaged and reconverted back to their triphosphate form to be reused. There are two primary enzymes involved in the salvage pathway: adenine phosphoribosyltransferase (APRT) and xanthine-guanine phosphoribosyltransferase (HGPRT) (figure 7.10). These enzymes will recombine the base (either adenine, guanine, or hypoxanthine) with PRPP to generate AMP, GMP, or IMP respectively. Adenosine is the only nucleoside that can be rephosphorylated to its monosphosphate form using adenosine kinase (figure 7.11). All other nucleosides must be degraded to their free base before they can be salvaged.', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.10,cell_bio/images/Figure 7.10.jpg,Figure 7.10: Nucleotide base salvage. Reaction catalyzed by HGPRT is clinically relevant as deficiencies can cause accumulation of uric acid.,"Excess uric acid, hyperuricemia, can cause the precipitation of uric acid crystals in the joints eliciting an inflammatory reaction causing acute pain or gout. The majority of individuals diagnosed with gout present due to underexcretion of uric acid. And this can be caused by the presence of other pathologies, such as lactic acidosis or the use of diuretics. Less common presentations of gout are associated with overproduction of uric acid, which can be caused by increased activity of PRPP synthetase or deficiency in purine recycling enzyme HGPRT caused by Lesch-Nyhan syndrome (figure 7.10).","{'2db2e660-1c37-4f4e-8ce1-fa92f6b103c6': 'Like amino acids, nucleotides contain nitrogen and must be degraded in a manner that allows for proper nitrogen disposal either through the urea cycle or by the synthesis of a nontoxic compound.', 'a81e5c48-c7b2-4ee4-9473-92a693b3e62c': 'Degradation of dietary nucleotides occurs in the gut, while nucleotides from de novo synthesis are degraded in the liver. The fundamental process involves the dismantling of the sugar, phosphate, and base structure into their own respective units (figure 7.9). In the case of purine degradation, the base is excreted in the form of uric acid. Purine nucleoside phosphorylase converts inosine and guanosine to their respective bases (hypoxanthine and guanine). Finally, xanthine oxidase will oxidize hypoxanthine to xanthine (guanine can be deaminated to xanthine), and xanthine can be further oxidized to uric acid by the same enzyme. Uric acid is excreted in the urine.', '2d94c725-7aa2-4f84-a09a-e818f8530169': 'Excess uric acid, hyperuricemia, can cause the precipitation of uric acid crystals in the joints eliciting an inflammatory reaction causing acute pain or gout. The majority of individuals diagnosed with gout present due to underexcretion of uric acid. And this can be caused by the presence of other pathologies, such as lactic acidosis\xa0or the use of diuretics. Less common presentations of gout are associated with overproduction of uric acid, which can be caused by increased activity of PRPP synthetase or deficiency in purine recycling enzyme HGPRT caused by Lesch-Nyhan syndrome (figure 7.10).', '39664de6-7ecf-4a24-96f5-a92f6809b6e3': 'The ability to recycle nucleotides is specifically important in the case of purines as de novo synthesis uses much more ATP than salvage. The degradation product of purine bases is uric acid, which is an insoluble compound, and accumulation can result in several clinical disorders as previously discussed. As such, purine bases can also undergo salvage reaction where bases are recycled and used in a new process. To reduce the\xa0amount of uric acid production, purines can be salvaged and reconverted back to their triphosphate form to be reused. There are two primary enzymes involved in the salvage pathway: adenine phosphoribosyltransferase (APRT) and xanthine-guanine phosphoribosyltransferase (HGPRT) (figure 7.10). These enzymes will recombine the base (either adenine, guanine, or hypoxanthine) with PRPP to generate AMP, GMP, or IMP respectively. Adenosine is the only nucleoside that can be rephosphorylated to its monosphosphate form using adenosine kinase (figure 7.11). All other nucleosides must be degraded to their free base before they can be salvaged.', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.12,cell_bio/images/Figure 7.12.jpg,Figure 7.12: Overview of pyrimidine synthesis. The reaction catalyzed by carbamoyl phosphate synthetase I is the regulatory enzyme of the pathway.,"In contrast to purine synthesis, the pyrimidine bases are synthesized before the ribose sugar and phosphate groups are added in the form of PRPP (figure 7.12). The initial step of the pathways involves the synthesis of carbamoyl phosphate from glutamine, carbon dioxide, and 2 ATP. Carbamoyl phosphate synthetase II (CSPII) catalyzes this reaction. (Note there is an analogous enzyme in the mitochondria for the urea cycle termed carbamoyl phosphate synthetase I, which also generates carbamoyl phosphate.) Of clinical importance is the intermediate orotate. Elevations of orotate (orotic acid) are consistent with enzymatic deficiencies in this pathway or urea cycle deficiencies such as a defect in ornithine transcarbamoylase. In the case of a urea cycle deficiency, an excess carbamoyl phosphate can enter pyrimidine synthesis leading to a build up of orotate. Following the synthesis of carbamoyl phosphate, a series of subsequent reactions yield uracil monosphosphate, which is the intermediate of pyrimidine synthesis.","{'681d9f3c-b496-4486-970e-dbfc9cafc734': 'In contrast to purine synthesis, the pyrimidine bases are synthesized before the ribose sugar and phosphate groups are added in the form of PRPP (figure 7.12). The initial step of the pathways involves the synthesis of carbamoyl phosphate from glutamine, carbon dioxide, and 2 ATP. Carbamoyl phosphate synthetase II (CSPII) catalyzes this reaction. (Note there is an analogous enzyme in the mitochondria for the urea cycle termed carbamoyl phosphate synthetase I, which also generates carbamoyl phosphate.)\xa0Of clinical importance is the intermediate orotate. Elevations of orotate (orotic acid) are consistent with enzymatic deficiencies in this pathway or urea cycle deficiencies such as a defect in ornithine transcarbamoylase. In the case of a urea cycle deficiency, an excess carbamoyl phosphate can enter pyrimidine synthesis leading to a build up of orotate. Following the synthesis of carbamoyl phosphate, a series of subsequent reactions yield uracil monosphosphate, which is the intermediate of pyrimidine synthesis.', 'b1bf9d85-f06d-41e5-b0c9-20e7bfa39dfc': 'UMP, much like IMP, serves as the intermediate to pyrimidine synthesis and can\xa0undergo sequential phosphorylation to form UTP, which can be converted to cytidine (CTP). Alternatively, UMP can be converted to a deoxy\xa0form (dUDP) to be used as substrate for the synthesis of thymidine. The conversion of dUDP to dTMP is catalyzed by thymidylate synthase, which requires folate (N5,N10 methylene tetrahydrofolate) as a methyl and hydrogen donor to complete this conversion (figure 7.13).', '6699d8e0-db95-4b6c-b7d3-72ca390dc812': 'Defects in pyrimidine synthesis most commonly present as an increase in orotic acid in the urine. Deficiencies in the attachment of PRPP to orotate (or the decarboxylation of orotate monosphosphate) can result in the accumulation of orotic acid;\xa0similarly deficiencies of the urea cycle, which lead to an accumulation of carbamoyl phosphate, can increase flux through pyrimidine synthesis and cause an increase in orotic acid. Accumulation of orotic acid is used as a clinical indicator of pyrimidine deficiencies or deficiencies in the urea cycle.', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.13,cell_bio/images/Figure 7.13.jpg,Figure 7.13: Interaction of thymidylate synthesis with the folate cycle. SHMT: serine hydroxymethyltransferase; DHFR: dihydrofolate reductase.,"UMP, much like IMP, serves as the intermediate to pyrimidine synthesis and can undergo sequential phosphorylation to form UTP, which can be converted to cytidine (CTP). Alternatively, UMP can be converted to a deoxy form (dUDP) to be used as substrate for the synthesis of thymidine. The conversion of dUDP to dTMP is catalyzed by thymidylate synthase, which requires folate (N5,N10 methylene tetrahydrofolate) as a methyl and hydrogen donor to complete this conversion (figure 7.13).","{'681d9f3c-b496-4486-970e-dbfc9cafc734': 'In contrast to purine synthesis, the pyrimidine bases are synthesized before the ribose sugar and phosphate groups are added in the form of PRPP (figure 7.12). The initial step of the pathways involves the synthesis of carbamoyl phosphate from glutamine, carbon dioxide, and 2 ATP. Carbamoyl phosphate synthetase II (CSPII) catalyzes this reaction. (Note there is an analogous enzyme in the mitochondria for the urea cycle termed carbamoyl phosphate synthetase I, which also generates carbamoyl phosphate.)\xa0Of clinical importance is the intermediate orotate. Elevations of orotate (orotic acid) are consistent with enzymatic deficiencies in this pathway or urea cycle deficiencies such as a defect in ornithine transcarbamoylase. In the case of a urea cycle deficiency, an excess carbamoyl phosphate can enter pyrimidine synthesis leading to a build up of orotate. Following the synthesis of carbamoyl phosphate, a series of subsequent reactions yield uracil monosphosphate, which is the intermediate of pyrimidine synthesis.', 'b1bf9d85-f06d-41e5-b0c9-20e7bfa39dfc': 'UMP, much like IMP, serves as the intermediate to pyrimidine synthesis and can\xa0undergo sequential phosphorylation to form UTP, which can be converted to cytidine (CTP). Alternatively, UMP can be converted to a deoxy\xa0form (dUDP) to be used as substrate for the synthesis of thymidine. The conversion of dUDP to dTMP is catalyzed by thymidylate synthase, which requires folate (N5,N10 methylene tetrahydrofolate) as a methyl and hydrogen donor to complete this conversion (figure 7.13).', '6699d8e0-db95-4b6c-b7d3-72ca390dc812': 'Defects in pyrimidine synthesis most commonly present as an increase in orotic acid in the urine. Deficiencies in the attachment of PRPP to orotate (or the decarboxylation of orotate monosphosphate) can result in the accumulation of orotic acid;\xa0similarly deficiencies of the urea cycle, which lead to an accumulation of carbamoyl phosphate, can increase flux through pyrimidine synthesis and cause an increase in orotic acid. Accumulation of orotic acid is used as a clinical indicator of pyrimidine deficiencies or deficiencies in the urea cycle.', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.13,cell_bio/images/Figure 7.13.jpg,Figure 7.13: Interaction of thymidylate synthesis with the folate cycle. SHMT: serine hydroxymethyltransferase; DHFR: dihydrofolate reductase.,"UMP, much like IMP, serves as the intermediate to pyrimidine synthesis and can undergo sequential phosphorylation to form UTP, which can be converted to cytidine (CTP). Alternatively, UMP can be converted to a deoxy form (dUDP) to be used as substrate for the synthesis of thymidine. The conversion of dUDP to dTMP is catalyzed by thymidylate synthase, which requires folate (N5,N10 methylene tetrahydrofolate) as a methyl and hydrogen donor to complete this conversion (figure 7.13).","{'681d9f3c-b496-4486-970e-dbfc9cafc734': 'In contrast to purine synthesis, the pyrimidine bases are synthesized before the ribose sugar and phosphate groups are added in the form of PRPP (figure 7.12). The initial step of the pathways involves the synthesis of carbamoyl phosphate from glutamine, carbon dioxide, and 2 ATP. Carbamoyl phosphate synthetase II (CSPII) catalyzes this reaction. (Note there is an analogous enzyme in the mitochondria for the urea cycle termed carbamoyl phosphate synthetase I, which also generates carbamoyl phosphate.)\xa0Of clinical importance is the intermediate orotate. Elevations of orotate (orotic acid) are consistent with enzymatic deficiencies in this pathway or urea cycle deficiencies such as a defect in ornithine transcarbamoylase. In the case of a urea cycle deficiency, an excess carbamoyl phosphate can enter pyrimidine synthesis leading to a build up of orotate. Following the synthesis of carbamoyl phosphate, a series of subsequent reactions yield uracil monosphosphate, which is the intermediate of pyrimidine synthesis.', 'b1bf9d85-f06d-41e5-b0c9-20e7bfa39dfc': 'UMP, much like IMP, serves as the intermediate to pyrimidine synthesis and can\xa0undergo sequential phosphorylation to form UTP, which can be converted to cytidine (CTP). Alternatively, UMP can be converted to a deoxy\xa0form (dUDP) to be used as substrate for the synthesis of thymidine. The conversion of dUDP to dTMP is catalyzed by thymidylate synthase, which requires folate (N5,N10 methylene tetrahydrofolate) as a methyl and hydrogen donor to complete this conversion (figure 7.13).', '6699d8e0-db95-4b6c-b7d3-72ca390dc812': 'Defects in pyrimidine synthesis most commonly present as an increase in orotic acid in the urine. Deficiencies in the attachment of PRPP to orotate (or the decarboxylation of orotate monosphosphate) can result in the accumulation of orotic acid;\xa0similarly deficiencies of the urea cycle, which lead to an accumulation of carbamoyl phosphate, can increase flux through pyrimidine synthesis and cause an increase in orotic acid. Accumulation of orotic acid is used as a clinical indicator of pyrimidine deficiencies or deficiencies in the urea cycle.', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.5,cell_bio/images/Figure 7.5.jpg,Figure 7.5: Overview of purine and pyrimidine bases.,"Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).","{'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.6,cell_bio/images/Figure 7.6.jpg,Figure 7.6: Synthesis of PRPP and regulation of PRPP synthetase.,"Ribose 5-phosphate is not used directly for either purine or pyrimidine synthesis, rather it is used to synthesize the “active pentose” — 5-phosphoribosyl-1-pyrophosphate (PRPP). The conversion is catalyzed by the enzyme phosphoribosyl-1-pyrophosphate (PRPP) synthase. PRPP is the activated five-carbon sugar used for nucleotide synthesis and provides both the sugar and phosphate group to nucleotides (figure 7.6).","{'b6aca37f-cfe6-4c57-a4dc-a48830ec8132': 'Ribose 5-phosphate is not used directly for either purine or pyrimidine synthesis, rather it is used to synthesize the “active pentose”\xa0—\xa05-phosphoribosyl-1-pyrophosphate (PRPP). The conversion is catalyzed by the enzyme phosphoribosyl-1-pyrophosphate (PRPP) synthase. PRPP is the activated five-carbon sugar used for nucleotide synthesis and provides both the sugar and phosphate group to nucleotides (figure 7.6).', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.7,cell_bio/images/Figure 7.7.jpg,Figure 7.7: Overview of purine synthesis. The reaction catalyzed by GPAT is the regulatory enzyme of the pathway.,"Purines are composed of a bicyclic structure that is synthesized from carbon and nitrogen donated from various compounds such as carbon dioxide, glycine, glutamine, aspartate, and tetrahydrofolate (TH4). The synthesis of purines starts with the synthesis of 5ʼphosphoribosylamine from PRPP and glutamine. The enzyme glutamine phosphoribosylpyrophate amidotransferase (GPAT) catalyzes this reaction and is the committed step in purine synthesis (figure 7.7). Synthesis continues for nine additional steps culminating in the synthesis of inosine monophosphate (IMP), which contains the base hypoxanthine. IMP is used to generate both AMP and GMP. The synthesis of both AMP and GMP requires energy in the form of the alternative base (i.e., the synthesis of GMP requires ATP while AMP synthesis requires energy in the form of GTP). The synthesis of AMP and GMP is regulated by feedback inhibition (figures 7.7 and 7.8). This allows for the maintenance of nucleotides in a relative ratio that is required for cellular processes. The generated nucleotide monophosphates can be converted to the di and triphosphate forms by nucleotide specific kinases, which will transfer phosphate groups to maintain a balance of the mono, di, and triphosphate forms.","{'6f5295f5-80c1-47c5-aa93-d8867fe62de9': 'Purines are composed of a bicyclic structure that is synthesized from carbon and nitrogen donated from various compounds such as\xa0carbon dioxide, glycine, glutamine, aspartate, and tetrahydrofolate (TH4). The synthesis of purines starts with the synthesis of 5ʼphosphoribosylamine from PRPP and glutamine. The enzyme glutamine phosphoribosylpyrophate amidotransferase (GPAT) catalyzes this reaction and is the committed step in purine synthesis (figure 7.7). Synthesis continues for nine\xa0additional steps culminating in the synthesis of inosine monophosphate (IMP), which contains the base hypoxanthine. IMP is used to generate both AMP and GMP. The synthesis of both AMP and GMP requires energy in the form of the alternative base\xa0(i.e., the synthesis of GMP requires ATP while AMP synthesis requires energy in the form of GTP). The synthesis of AMP and GMP is regulated by feedback inhibition (figures 7.7 and 7.8). This allows for the maintenance of nucleotides in a relative ratio that is required for cellular processes. The generated nucleotide monophosphates can be converted to the di and triphosphate forms by nucleotide specific kinases, which will transfer phosphate groups to maintain a balance of the mono, di,\xa0and triphosphate forms.', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.8,cell_bio/images/Figure 7.8.jpg,,Figure 7.8: Purine synthesis and regulation of glutamine: phosphoribosylpyrophosphate amidotransferase.,"{'15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.9,cell_bio/images/Figure 7.9.jpg,Figure 7.9: Breakdown of nucleotides.,"Degradation of dietary nucleotides occurs in the gut, while nucleotides from de novo synthesis are degraded in the liver. The fundamental process involves the dismantling of the sugar, phosphate, and base structure into their own respective units (figure 7.9). In the case of purine degradation, the base is excreted in the form of uric acid. Purine nucleoside phosphorylase converts inosine and guanosine to their respective bases (hypoxanthine and guanine). Finally, xanthine oxidase will oxidize hypoxanthine to xanthine (guanine can be deaminated to xanthine), and xanthine can be further oxidized to uric acid by the same enzyme. Uric acid is excreted in the urine.","{'2db2e660-1c37-4f4e-8ce1-fa92f6b103c6': 'Like amino acids, nucleotides contain nitrogen and must be degraded in a manner that allows for proper nitrogen disposal either through the urea cycle or by the synthesis of a nontoxic compound.', 'a81e5c48-c7b2-4ee4-9473-92a693b3e62c': 'Degradation of dietary nucleotides occurs in the gut, while nucleotides from de novo synthesis are degraded in the liver. The fundamental process involves the dismantling of the sugar, phosphate, and base structure into their own respective units (figure 7.9). In the case of purine degradation, the base is excreted in the form of uric acid. Purine nucleoside phosphorylase converts inosine and guanosine to their respective bases (hypoxanthine and guanine). Finally, xanthine oxidase will oxidize hypoxanthine to xanthine (guanine can be deaminated to xanthine), and xanthine can be further oxidized to uric acid by the same enzyme. Uric acid is excreted in the urine.', '2d94c725-7aa2-4f84-a09a-e818f8530169': 'Excess uric acid, hyperuricemia, can cause the precipitation of uric acid crystals in the joints eliciting an inflammatory reaction causing acute pain or gout. The majority of individuals diagnosed with gout present due to underexcretion of uric acid. And this can be caused by the presence of other pathologies, such as lactic acidosis\xa0or the use of diuretics. Less common presentations of gout are associated with overproduction of uric acid, which can be caused by increased activity of PRPP synthetase or deficiency in purine recycling enzyme HGPRT caused by Lesch-Nyhan syndrome (figure 7.10).', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.10,cell_bio/images/Figure 7.10.jpg,Figure 7.10: Nucleotide base salvage. Reaction catalyzed by HGPRT is clinically relevant as deficiencies can cause accumulation of uric acid.,"Excess uric acid, hyperuricemia, can cause the precipitation of uric acid crystals in the joints eliciting an inflammatory reaction causing acute pain or gout. The majority of individuals diagnosed with gout present due to underexcretion of uric acid. And this can be caused by the presence of other pathologies, such as lactic acidosis or the use of diuretics. Less common presentations of gout are associated with overproduction of uric acid, which can be caused by increased activity of PRPP synthetase or deficiency in purine recycling enzyme HGPRT caused by Lesch-Nyhan syndrome (figure 7.10).","{'2db2e660-1c37-4f4e-8ce1-fa92f6b103c6': 'Like amino acids, nucleotides contain nitrogen and must be degraded in a manner that allows for proper nitrogen disposal either through the urea cycle or by the synthesis of a nontoxic compound.', 'a81e5c48-c7b2-4ee4-9473-92a693b3e62c': 'Degradation of dietary nucleotides occurs in the gut, while nucleotides from de novo synthesis are degraded in the liver. The fundamental process involves the dismantling of the sugar, phosphate, and base structure into their own respective units (figure 7.9). In the case of purine degradation, the base is excreted in the form of uric acid. Purine nucleoside phosphorylase converts inosine and guanosine to their respective bases (hypoxanthine and guanine). Finally, xanthine oxidase will oxidize hypoxanthine to xanthine (guanine can be deaminated to xanthine), and xanthine can be further oxidized to uric acid by the same enzyme. Uric acid is excreted in the urine.', '2d94c725-7aa2-4f84-a09a-e818f8530169': 'Excess uric acid, hyperuricemia, can cause the precipitation of uric acid crystals in the joints eliciting an inflammatory reaction causing acute pain or gout. The majority of individuals diagnosed with gout present due to underexcretion of uric acid. And this can be caused by the presence of other pathologies, such as lactic acidosis\xa0or the use of diuretics. Less common presentations of gout are associated with overproduction of uric acid, which can be caused by increased activity of PRPP synthetase or deficiency in purine recycling enzyme HGPRT caused by Lesch-Nyhan syndrome (figure 7.10).', '39664de6-7ecf-4a24-96f5-a92f6809b6e3': 'The ability to recycle nucleotides is specifically important in the case of purines as de novo synthesis uses much more ATP than salvage. The degradation product of purine bases is uric acid, which is an insoluble compound, and accumulation can result in several clinical disorders as previously discussed. As such, purine bases can also undergo salvage reaction where bases are recycled and used in a new process. To reduce the\xa0amount of uric acid production, purines can be salvaged and reconverted back to their triphosphate form to be reused. There are two primary enzymes involved in the salvage pathway: adenine phosphoribosyltransferase (APRT) and xanthine-guanine phosphoribosyltransferase (HGPRT) (figure 7.10). These enzymes will recombine the base (either adenine, guanine, or hypoxanthine) with PRPP to generate AMP, GMP, or IMP respectively. Adenosine is the only nucleoside that can be rephosphorylated to its monosphosphate form using adenosine kinase (figure 7.11). All other nucleosides must be degraded to their free base before they can be salvaged.', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.11,cell_bio/images/Figure 7.11.jpg,,Figure 7.11: Nucleotide specific pathways for base salvage.,"{'15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.12,cell_bio/images/Figure 7.12.jpg,Figure 7.12: Overview of pyrimidine synthesis. The reaction catalyzed by carbamoyl phosphate synthetase I is the regulatory enzyme of the pathway.,"In contrast to purine synthesis, the pyrimidine bases are synthesized before the ribose sugar and phosphate groups are added in the form of PRPP (figure 7.12). The initial step of the pathways involves the synthesis of carbamoyl phosphate from glutamine, carbon dioxide, and 2 ATP. Carbamoyl phosphate synthetase II (CSPII) catalyzes this reaction. (Note there is an analogous enzyme in the mitochondria for the urea cycle termed carbamoyl phosphate synthetase I, which also generates carbamoyl phosphate.) Of clinical importance is the intermediate orotate. Elevations of orotate (orotic acid) are consistent with enzymatic deficiencies in this pathway or urea cycle deficiencies such as a defect in ornithine transcarbamoylase. In the case of a urea cycle deficiency, an excess carbamoyl phosphate can enter pyrimidine synthesis leading to a build up of orotate. Following the synthesis of carbamoyl phosphate, a series of subsequent reactions yield uracil monosphosphate, which is the intermediate of pyrimidine synthesis.","{'681d9f3c-b496-4486-970e-dbfc9cafc734': 'In contrast to purine synthesis, the pyrimidine bases are synthesized before the ribose sugar and phosphate groups are added in the form of PRPP (figure 7.12). The initial step of the pathways involves the synthesis of carbamoyl phosphate from glutamine, carbon dioxide, and 2 ATP. Carbamoyl phosphate synthetase II (CSPII) catalyzes this reaction. (Note there is an analogous enzyme in the mitochondria for the urea cycle termed carbamoyl phosphate synthetase I, which also generates carbamoyl phosphate.)\xa0Of clinical importance is the intermediate orotate. Elevations of orotate (orotic acid) are consistent with enzymatic deficiencies in this pathway or urea cycle deficiencies such as a defect in ornithine transcarbamoylase. In the case of a urea cycle deficiency, an excess carbamoyl phosphate can enter pyrimidine synthesis leading to a build up of orotate. Following the synthesis of carbamoyl phosphate, a series of subsequent reactions yield uracil monosphosphate, which is the intermediate of pyrimidine synthesis.', 'b1bf9d85-f06d-41e5-b0c9-20e7bfa39dfc': 'UMP, much like IMP, serves as the intermediate to pyrimidine synthesis and can\xa0undergo sequential phosphorylation to form UTP, which can be converted to cytidine (CTP). Alternatively, UMP can be converted to a deoxy\xa0form (dUDP) to be used as substrate for the synthesis of thymidine. The conversion of dUDP to dTMP is catalyzed by thymidylate synthase, which requires folate (N5,N10 methylene tetrahydrofolate) as a methyl and hydrogen donor to complete this conversion (figure 7.13).', '6699d8e0-db95-4b6c-b7d3-72ca390dc812': 'Defects in pyrimidine synthesis most commonly present as an increase in orotic acid in the urine. Deficiencies in the attachment of PRPP to orotate (or the decarboxylation of orotate monosphosphate) can result in the accumulation of orotic acid;\xa0similarly deficiencies of the urea cycle, which lead to an accumulation of carbamoyl phosphate, can increase flux through pyrimidine synthesis and cause an increase in orotic acid. Accumulation of orotic acid is used as a clinical indicator of pyrimidine deficiencies or deficiencies in the urea cycle.', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 7.4,cell_bio/images/Figure 7.4.jpg,Figure 7.4: Basic structure of nucleotides.,"Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three functional groups: a sugar, a base, and phosphate (figure 7.4).","{'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', '15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.'}"
Figure 6.2,cell_bio/images/Figure 6.2.jpg,Figure 6.2: Cholesterol synthetic pathway.,"Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four stages (figure 6.2); however, only the first stage is regulated and will be focused on here.","{'15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.', '7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.3,cell_bio/images/Figure 6.3.jpg,Figure 6.3: Regulatory step catalyzed by HMG-CoA reductase.,"The first stage of cholesterol synthesis leads to the production of the intermediate mevalonate. The synthesis of mevalonate is the committed, rate-limiting step in cholesterol formation. In this reaction, two molecules of acetyl-CoA condense, forming acetoacetyl-CoA, which then condenses with a third molecule of acetyl-CoA to yield the six-carbon compound β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) (figure 6.3) (the cytosolic HMG-CoA synthase in this reaction is distinct from the mitochondrial HMG-CoA synthase that catalyzes a similar reaction involved in production of ketone bodies). The committed step and major point of regulation of cholesterol synthesis involves reduction of HMG-CoA to mevalonate, in a reaction that is catalyzed by HMG-CoA reductase.","{'3c0c346b-71a3-475e-a7c0-179b405e4362': 'The first stage of cholesterol synthesis leads to the production of the intermediate mevalonate. The synthesis of mevalonate is the committed, rate-limiting step in cholesterol formation. In this reaction, two molecules of acetyl-CoA condense, forming acetoacetyl-CoA, which then condenses with a third molecule of acetyl-CoA to yield the six-carbon compound β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) (figure 6.3) (the cytosolic HMG-CoA synthase in this reaction is distinct from the mitochondrial HMG-CoA synthase that catalyzes a similar reaction involved in production of ketone bodies). The committed step and major point of regulation of cholesterol synthesis involves reduction of HMG-CoA to mevalonate, in a reaction that is catalyzed by HMG-CoA reductase.', '98a86980-39f3-4f2f-819a-955e68ab9df8': 'The subsequent steps of the pathway proceed largely unregulated, and mevalonate is used to synthesize isoprenoid units (five-carbon units). These five-carbon chains are joined in a head-to-tail fashion generating squalene, thirty-carbons, which undergoes a cyclization reaction after epoxidation. The cyclized product, lanosterol, undergoes several reactions to generate the final product, cholesterol.', '7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.'}"
Figure 6.4,cell_bio/images/Figure 6.4.jpg,Figure 6.4: Regulation of cholesterol synthesis.,The major regulatory enzyme for cholesterol synthesis is HMG-CoA reductase. This enzyme is tightly controlled by many different types of regulation and can be influenced by hormonal changes as well as cellular needs (figure 6.4). This is also one of the primary pharmacological targets for the management of hypercholesterolemia. The statins are direct inhibitors of this enzyme.,"{'80e88c2d-7741-433c-8d0d-839e47a7d52e': 'The major regulatory enzyme for cholesterol synthesis is HMG-CoA reductase. This enzyme is tightly controlled by many different types of regulation and can be influenced by hormonal changes as well as cellular needs (figure 6.4). This is also one of the primary pharmacological targets for the management of hypercholesterolemia. The statins are direct inhibitors of this enzyme.', '8b7da794-28e6-4af4-af30-215c83639998': 'Control of transcriptional initiation is a primary means used to regulate gene expression in eukaryotic organisms. Most eukaryotic genes are controlled at the level of transcription by proteins (trans-acting factors) that interact with specific gene sequences (cis-acting regulatory sequences).', '214551e2-61ed-4790-a279-6c92c53209f3': 'The rate of synthesis of HMG-CoA reductase messenger RNA (mRNA) is controlled by one of the family of sterol-regulatory element-binding proteins (SREBPs). SREBPs are integral proteins of the endoplasmic reticulum (ER). When cholesterol levels in the cell are high, the SREBP is bound to SCAP (SREBP cleavage activating protein) in the ER membrane. When cholesterol levels drop, the sterol leaves its SCAP-binding site, and the SREBP:SCAP complex is transported to the Golgi apparatus. Within the Golgi, two proteolytic cleavages occur, which release the N-terminal transcription factor domain from the Golgi membrane. Once released, the active amino terminal component travels to the nucleus to bind to sterol-regulatory elements (SREs). Binding to this upstream element enhances transcription of the HMG-CoA reductase gene. The soluble SREBPs are rapidly turned over and need to be continuously produced to stimulate reductase mRNA transcription effectively. As cholesterol levels in the cell increase, due to de novo synthesis, cholesterol will bind to SCAP and prevent translocation of the complex to the Golgi, leading to a decrease in transcription of the reductase gene and thus less reductase protein being produced (figure 6.4).', '7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.'}"
Figure 6.4,cell_bio/images/Figure 6.4.jpg,Figure 6.4: Regulation of cholesterol synthesis.,The major regulatory enzyme for cholesterol synthesis is HMG-CoA reductase. This enzyme is tightly controlled by many different types of regulation and can be influenced by hormonal changes as well as cellular needs (figure 6.4). This is also one of the primary pharmacological targets for the management of hypercholesterolemia. The statins are direct inhibitors of this enzyme.,"{'80e88c2d-7741-433c-8d0d-839e47a7d52e': 'The major regulatory enzyme for cholesterol synthesis is HMG-CoA reductase. This enzyme is tightly controlled by many different types of regulation and can be influenced by hormonal changes as well as cellular needs (figure 6.4). This is also one of the primary pharmacological targets for the management of hypercholesterolemia. The statins are direct inhibitors of this enzyme.', '8b7da794-28e6-4af4-af30-215c83639998': 'Control of transcriptional initiation is a primary means used to regulate gene expression in eukaryotic organisms. Most eukaryotic genes are controlled at the level of transcription by proteins (trans-acting factors) that interact with specific gene sequences (cis-acting regulatory sequences).', '214551e2-61ed-4790-a279-6c92c53209f3': 'The rate of synthesis of HMG-CoA reductase messenger RNA (mRNA) is controlled by one of the family of sterol-regulatory element-binding proteins (SREBPs). SREBPs are integral proteins of the endoplasmic reticulum (ER). When cholesterol levels in the cell are high, the SREBP is bound to SCAP (SREBP cleavage activating protein) in the ER membrane. When cholesterol levels drop, the sterol leaves its SCAP-binding site, and the SREBP:SCAP complex is transported to the Golgi apparatus. Within the Golgi, two proteolytic cleavages occur, which release the N-terminal transcription factor domain from the Golgi membrane. Once released, the active amino terminal component travels to the nucleus to bind to sterol-regulatory elements (SREs). Binding to this upstream element enhances transcription of the HMG-CoA reductase gene. The soluble SREBPs are rapidly turned over and need to be continuously produced to stimulate reductase mRNA transcription effectively. As cholesterol levels in the cell increase, due to de novo synthesis, cholesterol will bind to SCAP and prevent translocation of the complex to the Golgi, leading to a decrease in transcription of the reductase gene and thus less reductase protein being produced (figure 6.4).', '7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.'}"
Figure 6.5,cell_bio/images/Figure 6.5.jpg,Figure 6.5: Esterification of cholesterol by LCAT.,"Cholesterol is an amphipathic molecule (containing both polar and nonpolar regions), and in its native state it can freely diffuse through membranes. In order to be stored in cells, cholesterol must be modified by increasing its hydrophobicity. Cholesterol ester production in the liver is catalyzed by acyl-CoA‒cholesterol acyl transferase (ACAT). ACAT catalyzes the transfer of a fatty acid from coenzyme A to the hydroxyl group on carbon 3 of cholesterol. (This is similar to the reaction catalyzed by lecithin:cholesterol acyltransferase within the plasma associated with HDLs; figure 6.5.) Regardless of whether the additional group is an acyl chain or phosphatidylcholine, the resulting cholesterol esters are more hydrophobic than free cholesterol. The liver packages some of the esterified cholesterol into the hollow core of lipoproteins, primarily VLDL. VLDL is secreted from the hepatocyte into the blood and transports the cholesterol esters (triacylglycerols, phospholipids, apoproteins, etc.) to the tissues that require greater amounts of cholesterol than they can synthesize de novo. These tissues then use the cholesterol for the synthesis of membranes, the formation of steroid hormones, and the biosynthesis of vitamin D.","{'9ede71cf-1469-48e1-be43-fd8d7171b0fb': 'Cholesterol is an amphipathic molecule (containing both polar and nonpolar regions), and in its native state it can freely diffuse through membranes. In order to be stored in cells, cholesterol must be modified by increasing its hydrophobicity. Cholesterol ester production in the liver is catalyzed by acyl-CoA‒cholesterol acyl transferase (ACAT). ACAT catalyzes the transfer of a fatty acid from coenzyme A to the hydroxyl group on carbon 3 of cholesterol. (This is similar to the reaction catalyzed by lecithin:cholesterol acyltransferase within the plasma associated with HDLs; figure 6.5.)\xa0Regardless of whether the additional group is an acyl chain or phosphatidylcholine, the resulting cholesterol esters are more hydrophobic than free cholesterol. The liver packages some of the esterified cholesterol into the hollow core of lipoproteins, primarily VLDL. VLDL is secreted from the hepatocyte into the blood and transports the cholesterol esters (triacylglycerols, phospholipids, apoproteins, etc.) to the tissues that require greater amounts of cholesterol than they can synthesize de novo. These tissues then use the cholesterol for the synthesis of membranes,\xa0the formation of steroid hormones, and\xa0the biosynthesis of vitamin D.', '7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.'}"
Figure 6.1,cell_bio/images/Figure 6.1.jpg,,Figure 6.1: Structure of cholesterol.,"{'7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.'}"
Figure 6.2,cell_bio/images/Figure 6.2.jpg,Figure 6.2: Cholesterol synthetic pathway.,"Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four stages (figure 6.2); however, only the first stage is regulated and will be focused on here.","{'15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.', '7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.3,cell_bio/images/Figure 6.3.jpg,Figure 6.3: Regulatory step catalyzed by HMG-CoA reductase.,"The first stage of cholesterol synthesis leads to the production of the intermediate mevalonate. The synthesis of mevalonate is the committed, rate-limiting step in cholesterol formation. In this reaction, two molecules of acetyl-CoA condense, forming acetoacetyl-CoA, which then condenses with a third molecule of acetyl-CoA to yield the six-carbon compound β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) (figure 6.3) (the cytosolic HMG-CoA synthase in this reaction is distinct from the mitochondrial HMG-CoA synthase that catalyzes a similar reaction involved in production of ketone bodies). The committed step and major point of regulation of cholesterol synthesis involves reduction of HMG-CoA to mevalonate, in a reaction that is catalyzed by HMG-CoA reductase.","{'3c0c346b-71a3-475e-a7c0-179b405e4362': 'The first stage of cholesterol synthesis leads to the production of the intermediate mevalonate. The synthesis of mevalonate is the committed, rate-limiting step in cholesterol formation. In this reaction, two molecules of acetyl-CoA condense, forming acetoacetyl-CoA, which then condenses with a third molecule of acetyl-CoA to yield the six-carbon compound β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) (figure 6.3) (the cytosolic HMG-CoA synthase in this reaction is distinct from the mitochondrial HMG-CoA synthase that catalyzes a similar reaction involved in production of ketone bodies). The committed step and major point of regulation of cholesterol synthesis involves reduction of HMG-CoA to mevalonate, in a reaction that is catalyzed by HMG-CoA reductase.', '98a86980-39f3-4f2f-819a-955e68ab9df8': 'The subsequent steps of the pathway proceed largely unregulated, and mevalonate is used to synthesize isoprenoid units (five-carbon units). These five-carbon chains are joined in a head-to-tail fashion generating squalene, thirty-carbons, which undergoes a cyclization reaction after epoxidation. The cyclized product, lanosterol, undergoes several reactions to generate the final product, cholesterol.', '7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.'}"
Figure 6.5,cell_bio/images/Figure 6.5.jpg,Figure 6.5: Esterification of cholesterol by LCAT.,"Cholesterol is an amphipathic molecule (containing both polar and nonpolar regions), and in its native state it can freely diffuse through membranes. In order to be stored in cells, cholesterol must be modified by increasing its hydrophobicity. Cholesterol ester production in the liver is catalyzed by acyl-CoA‒cholesterol acyl transferase (ACAT). ACAT catalyzes the transfer of a fatty acid from coenzyme A to the hydroxyl group on carbon 3 of cholesterol. (This is similar to the reaction catalyzed by lecithin:cholesterol acyltransferase within the plasma associated with HDLs; figure 6.5.) Regardless of whether the additional group is an acyl chain or phosphatidylcholine, the resulting cholesterol esters are more hydrophobic than free cholesterol. The liver packages some of the esterified cholesterol into the hollow core of lipoproteins, primarily VLDL. VLDL is secreted from the hepatocyte into the blood and transports the cholesterol esters (triacylglycerols, phospholipids, apoproteins, etc.) to the tissues that require greater amounts of cholesterol than they can synthesize de novo. These tissues then use the cholesterol for the synthesis of membranes, the formation of steroid hormones, and the biosynthesis of vitamin D.","{'9ede71cf-1469-48e1-be43-fd8d7171b0fb': 'Cholesterol is an amphipathic molecule (containing both polar and nonpolar regions), and in its native state it can freely diffuse through membranes. In order to be stored in cells, cholesterol must be modified by increasing its hydrophobicity. Cholesterol ester production in the liver is catalyzed by acyl-CoA‒cholesterol acyl transferase (ACAT). ACAT catalyzes the transfer of a fatty acid from coenzyme A to the hydroxyl group on carbon 3 of cholesterol. (This is similar to the reaction catalyzed by lecithin:cholesterol acyltransferase within the plasma associated with HDLs; figure 6.5.)\xa0Regardless of whether the additional group is an acyl chain or phosphatidylcholine, the resulting cholesterol esters are more hydrophobic than free cholesterol. The liver packages some of the esterified cholesterol into the hollow core of lipoproteins, primarily VLDL. VLDL is secreted from the hepatocyte into the blood and transports the cholesterol esters (triacylglycerols, phospholipids, apoproteins, etc.) to the tissues that require greater amounts of cholesterol than they can synthesize de novo. These tissues then use the cholesterol for the synthesis of membranes,\xa0the formation of steroid hormones, and\xa0the biosynthesis of vitamin D.', '7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.'}"
Figure 6.4,cell_bio/images/Figure 6.4.jpg,Figure 6.4: Regulation of cholesterol synthesis.,The major regulatory enzyme for cholesterol synthesis is HMG-CoA reductase. This enzyme is tightly controlled by many different types of regulation and can be influenced by hormonal changes as well as cellular needs (figure 6.4). This is also one of the primary pharmacological targets for the management of hypercholesterolemia. The statins are direct inhibitors of this enzyme.,"{'80e88c2d-7741-433c-8d0d-839e47a7d52e': 'The major regulatory enzyme for cholesterol synthesis is HMG-CoA reductase. This enzyme is tightly controlled by many different types of regulation and can be influenced by hormonal changes as well as cellular needs (figure 6.4). This is also one of the primary pharmacological targets for the management of hypercholesterolemia. The statins are direct inhibitors of this enzyme.', '8b7da794-28e6-4af4-af30-215c83639998': 'Control of transcriptional initiation is a primary means used to regulate gene expression in eukaryotic organisms. Most eukaryotic genes are controlled at the level of transcription by proteins (trans-acting factors) that interact with specific gene sequences (cis-acting regulatory sequences).', '214551e2-61ed-4790-a279-6c92c53209f3': 'The rate of synthesis of HMG-CoA reductase messenger RNA (mRNA) is controlled by one of the family of sterol-regulatory element-binding proteins (SREBPs). SREBPs are integral proteins of the endoplasmic reticulum (ER). When cholesterol levels in the cell are high, the SREBP is bound to SCAP (SREBP cleavage activating protein) in the ER membrane. When cholesterol levels drop, the sterol leaves its SCAP-binding site, and the SREBP:SCAP complex is transported to the Golgi apparatus. Within the Golgi, two proteolytic cleavages occur, which release the N-terminal transcription factor domain from the Golgi membrane. Once released, the active amino terminal component travels to the nucleus to bind to sterol-regulatory elements (SREs). Binding to this upstream element enhances transcription of the HMG-CoA reductase gene. The soluble SREBPs are rapidly turned over and need to be continuously produced to stimulate reductase mRNA transcription effectively. As cholesterol levels in the cell increase, due to de novo synthesis, cholesterol will bind to SCAP and prevent translocation of the complex to the Golgi, leading to a decrease in transcription of the reductase gene and thus less reductase protein being produced (figure 6.4).', '7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.'}"
Figure 6.6,cell_bio/images/Figure 6.6.jpg,Figure 6.6: Overview of lipoprotein size and structure.,"As such, a transport system for distribution of major lipids is in place to aid in the movement of these compounds. This system involves the family of lipoproteins, which have distinct roles in carrying dietary lipids, lipids synthesized through de novo mechanism in the liver, and for reverse cholesterol transport (figure 6.6).","{'1e1074ac-ef70-43ce-b84d-7d0f9ba0e939': 'As such, a transport system for distribution of major lipids is in place to aid in the movement of these compounds. This system involves the family of lipoproteins, which have distinct roles in carrying dietary lipids, lipids synthesized through de novo mechanism in the liver, and for reverse cholesterol transport (figure 6.6).', '6e690769-0660-48bf-a4ff-78208ea290a8': 'In addition to the lipid components of lipoproteins, they contain protein components termed apoproteins. The complement of apoproteins on each lipoprotein is unique and is a distinguishing characteristic of each family of lipoproteins. The apoproteins (“apo” describes the protein within the shell of the particle in its lipid-free form) not only add to the hydrophilicity and structural stability of the particle, but they have other functions as well: (1) They activate certain enzymes required for normal lipoprotein metabolism, and (2) they act as ligands on the surface of the lipoprotein that target specific receptors on peripheral tissues that require lipoprotein delivery for their innate cellular functions.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.7,cell_bio/images/Figure 6.7.jpg,Figure 6.7: Transport of dietary lipids via chylomicrons.,"Fatty acids, which are stored as TAGs, serve as fuels, providing the body with its major source of energy. TAGs are the major dietary lipids and are digested in the lumen of the intestine. The initial digestive products, free fatty acids and 2-monoacylglycerol, are reconverted to TAGs in intestinal epithelial cells, packaged in lipoproteins known as chylomicrons, and secreted into the lymph (figure 6.7).","{'19e4374e-a9e9-4532-8402-33b92129522a': 'Fatty acids, which are stored as TAGs, serve as fuels, providing the body with its major source of energy. TAGs are the major dietary lipids and are digested in the lumen of the intestine. The initial digestive products, free fatty acids and 2-monoacylglycerol, are reconverted to TAGs in intestinal epithelial cells, packaged in lipoproteins known as chylomicrons, and secreted into the lymph (figure 6.7).', '61f7c54a-6611-483c-81ff-6f65a3d6b334': 'Chylomicrons are the largest lipoproteins and contain cholesterol and fat-soluble vitamins, in addition to their major component, dietary TAGs. The major apoprotein associated with chylomicrons as they leave the intestinal cells is ApoB-48. (The B-48 apoprotein is structurally and genetically related to the B-100 apoprotein synthesized in the liver that serves as a major protein of VLDL.)\xa0Microsomal transfer protein (MTP) aids in the loading of apoB-48 protein onto the chylomicron before the nascent chylomicron is secreted. Nascent chylomicrons are secreted by the intestinal epithelial cells into the chyle of the lymphatic system and enter the blood through the thoracic duct. Nascent chylomicrons begin to enter the blood within one to two hours after the start of a meal; as the meal is digested and absorbed, they continue to enter the blood for many hours. Chylomicron maturation occurs in circulation as they accept additional apoproteins from high-density lipoprotein (HDL) (figures 6.7 and 6.10).', '1fb9aa77-009e-4ae1-97dc-ae12f1e692b5': 'HDL predominantly transfers apoproteins E and CII to the nascent chylomicrons. ApoE is recognized by membrane receptors, and this interaction allows apoE-bearing lipoproteins to enter these cells by endocytosis; once inside the cell the particle is broken down through a lysosomal-mediated process. ApoCII acts as an activator of lipoprotein lipase (LPL), the enzyme on capillary endothelial cells, which digests the TAGs of the chylomicrons and VLDLs in the blood.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.8,cell_bio/images/Figure 6.8.jpg,Figure 6.8: Transport of TAGs from de novo synthesis using VLDL.,"Very low-density lipoprotein (VLDL) is produced in the liver, mainly from lipogenesis. Lipogenesis is an insulin-stimulated process through which excess glucose is converted to fatty acids (section 4.4), which are subsequently esterified to glycerol to form TAGs. TAGs produced in the smooth endoplasmic reticulum of the liver are packaged with cholesterol, phospholipids, and proteins (synthesized in the rough endoplasmic reticulum) to form VLDLs. Apart from their initial origin, VLDLs and chylomicrons are very similar with respect to maturation and activity. The VLDL particles acquire apoB-100 through an MTP-mediated reaction before being released into circulation. Within circulation, VLDLs also interact with HDL and acquire ApoCII and ApoE (figure 6.8). Like chylomicrons, VLDLs are also hydrolyzed by lipoprotein lipase (LPL), and the released fatty acids can be taken up by muscle and other tissues to be oxidized. After a meal, these fatty acids are also taken up by adipose tissue and stored as TAGs. In summary, the process of dietary versus de novo lipid transport has many parallels, which are compared in figure 6.9.","{'84b462ad-96d0-472f-8da4-c09a5ab9a59a': 'Very low-density lipoprotein (VLDL) is produced in the liver, mainly from lipogenesis. Lipogenesis is an insulin-stimulated process through which excess glucose is converted to fatty acids (section 4.4), which are subsequently esterified to glycerol to form TAGs. TAGs produced in the smooth endoplasmic reticulum of the liver are packaged with cholesterol, phospholipids, and proteins (synthesized in the rough endoplasmic reticulum) to form VLDLs. Apart from their initial origin, VLDLs and chylomicrons are very similar with respect to maturation and activity. The VLDL particles acquire apoB-100 through an MTP-mediated reaction before being released into circulation. Within circulation, VLDLs also interact with HDL and acquire ApoCII and ApoE (figure 6.8). Like chylomicrons, VLDLs are also hydrolyzed by lipoprotein lipase (LPL), and the released fatty acids can be taken up by muscle and other tissues to be oxidized. After a meal, these fatty acids are also taken up by adipose tissue and stored as TAGs. In summary, the process of dietary versus\xa0de novo lipid transport has many parallels, which are compared in figure 6.9.', 'a7832ccd-7df7-4aa2-8c23-274080dc5d9e': 'Although VLDLs and chylomicrons have similar roles in the cell, it is important to keep them distinct. The comparison between the transport of exogenous lipids and endogenous lipids is illustrated in figure 6.9. Because the fatty acids stored in adipose tissue come both from chylomicrons and VLDL, we produce our major fat stores both from dietary fat (which is transported by chylomicrons) and dietary sugar (which can be synthesized into TAGs and packaged into VLDL). An excess of dietary protein also can be used to produce the fatty acids for VLDL synthesis. Clinically, measured triacylglycerols (under fasting conditions) will largely reflect the VLDL contribution.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.9,cell_bio/images/Figure 6.9.jpg,Figure 6.9: Comparison of the role of chylomicrons and VLDLs in lipid transport.,"Although VLDLs and chylomicrons have similar roles in the cell, it is important to keep them distinct. The comparison between the transport of exogenous lipids and endogenous lipids is illustrated in figure 6.9. Because the fatty acids stored in adipose tissue come both from chylomicrons and VLDL, we produce our major fat stores both from dietary fat (which is transported by chylomicrons) and dietary sugar (which can be synthesized into TAGs and packaged into VLDL). An excess of dietary protein also can be used to produce the fatty acids for VLDL synthesis. Clinically, measured triacylglycerols (under fasting conditions) will largely reflect the VLDL contribution.","{'84b462ad-96d0-472f-8da4-c09a5ab9a59a': 'Very low-density lipoprotein (VLDL) is produced in the liver, mainly from lipogenesis. Lipogenesis is an insulin-stimulated process through which excess glucose is converted to fatty acids (section 4.4), which are subsequently esterified to glycerol to form TAGs. TAGs produced in the smooth endoplasmic reticulum of the liver are packaged with cholesterol, phospholipids, and proteins (synthesized in the rough endoplasmic reticulum) to form VLDLs. Apart from their initial origin, VLDLs and chylomicrons are very similar with respect to maturation and activity. The VLDL particles acquire apoB-100 through an MTP-mediated reaction before being released into circulation. Within circulation, VLDLs also interact with HDL and acquire ApoCII and ApoE (figure 6.8). Like chylomicrons, VLDLs are also hydrolyzed by lipoprotein lipase (LPL), and the released fatty acids can be taken up by muscle and other tissues to be oxidized. After a meal, these fatty acids are also taken up by adipose tissue and stored as TAGs. In summary, the process of dietary versus\xa0de novo lipid transport has many parallels, which are compared in figure 6.9.', 'a7832ccd-7df7-4aa2-8c23-274080dc5d9e': 'Although VLDLs and chylomicrons have similar roles in the cell, it is important to keep them distinct. The comparison between the transport of exogenous lipids and endogenous lipids is illustrated in figure 6.9. Because the fatty acids stored in adipose tissue come both from chylomicrons and VLDL, we produce our major fat stores both from dietary fat (which is transported by chylomicrons) and dietary sugar (which can be synthesized into TAGs and packaged into VLDL). An excess of dietary protein also can be used to produce the fatty acids for VLDL synthesis. Clinically, measured triacylglycerols (under fasting conditions) will largely reflect the VLDL contribution.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.11,cell_bio/images/Figure 6.11.jpg,Figure 6.11: Uptake of LDL and regulation of cholesterol synthesis.,"Much like the conversion of chylomicrons to chylomicron remnants, LPL converts VLDL to an intermediate-density lipoprotein (IDL). IDLs, having relatively low TAG content, are taken up by the liver through endocytosis, and degraded lysosomes as discussed above. IDL may also be converted to low-density lipoprotein (LDL) by further digestion of TAGs. Endocytosis of LDL occurs in peripheral tissues (and the liver) and is the major means of cholesterol transport and delivery to peripheral tissues. LDLs taken up by peripheral tissues will help increase the amount of intracellular cholesterol and therefore influence the regulation of HMG-CoA reductase (figure 6.11).","{'a2a785be-d3f0-4ec2-bd4f-1ba416acea3b': 'Much like the conversion of chylomicrons to chylomicron remnants, LPL converts VLDL to an intermediate-density lipoprotein (IDL). IDLs, having relatively low TAG content, are taken up by the liver through endocytosis, and degraded lysosomes as discussed above. IDL may also be converted to low-density lipoprotein (LDL) by further digestion of TAGs. Endocytosis of LDL occurs in peripheral tissues (and the liver) and is the major means of cholesterol transport and delivery to peripheral tissues. LDLs taken up by peripheral tissues will help increase the amount of intracellular cholesterol and therefore influence the regulation of HMG-CoA reductase (figure 6.11).', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.10,cell_bio/images/Figure 6.10.jpg,Figure 6.10: Interaction of chylomicrons and VLDL with HDL in circulation.,"HDLs can also be generated through budding of apoA from chylomicrons and VLDL particles or from free apoAI, which may be shed from other circulating lipoproteins. In this case, the apoAI acquires cholesterol and phospholipids from other lipoproteins and cell membranes, forming a nascent-like HDL particle within the circulation (figure 6.10).","{'dc9e84b3-c161-4992-8d11-23080026ca9f': 'The primary function of high-density lipoprotein (HDL) is to transport excess cholesterol obtained from peripheral tissues to the liver. HDL also has other roles integral to lipid transport such as exchanging proteins and lipids with chylomicrons and VLDL. HDL particles can be created by several mechanisms, however, nascent HDLs are primarily secreted from the liver and intestine as a relatively small particles whose shell, like that of other lipoproteins, contains phospholipids, free cholesterol, and a variety of apoproteins, specifically apoAI, apoAII, apoCI, and apoCII. Very low levels of triacylglycerols or cholesterol esters are found in the hollow core of this early, or nascent, version of HDL.', 'dad1f10e-9b0f-4a5e-8937-a872f4bc7524': 'HDLs can also be generated through budding of apoA from chylomicrons and VLDL particles or from free apoAI, which may be shed from other circulating lipoproteins. In this case, the apoAI acquires cholesterol and phospholipids from other lipoproteins and cell membranes, forming a nascent-like HDL particle within the circulation (figure 6.10).', '6b8c0c52-ebfd-41fb-abfc-2009813205ed': 'In the process of maturation, the nascent HDL particles accumulate phospholipids and cholesterol from cells lining the blood vessels. As the central hollow core of nascent HDL progressively fills with cholesterol esters, HDL takes on a more globular shape to eventually form the mature HDL particle. A major benefit of HDL particles derives from their ability to remove cholesterol from cholesterol-laden cells and to return the cholesterol to the liver, a process known as reverse cholesterol transport. This is particularly beneficial in vascular tissue; by reducing cellular cholesterol levels in the subintimal space, the likelihood that foam cells (lipid-laden macrophages that engulf oxidized LDL cholesterol) will form within the blood vessel wall is reduced.', '72a76514-97d2-4758-b87f-7f78d35977d4': 'Reverse cholesterol transport requires a movement of cholesterol from cellular stores to the lipoprotein particle. Cells contain the protein ABCA1 (ATP-binding cassette protein 1) that uses ATP hydrolysis to move cholesterol from the inner leaflet of the membrane to the outer leaflet. Once the cholesterol has reached the outer membrane leaflet, the HDL particle can accept it. To trap the cholesterol within the HDL core, the HDL particle acquires the enzyme lecithin-cholesterol acyltransferase (LCAT) from the circulation (figure 6.10). LCAT catalyzes the transfer of a fatty acid from the 2-position of lecithin (phosphatidylcholine) in the phospholipid shell of the particle to the 3-hydroxyl group of cholesterol, forming a cholesterol ester. The cholesterol esters form the core of the HDL particle and are\xa0no longer free to return to the cell.', 'e9abdebf-773e-4179-bf7b-20f6fe7cedfd': 'Mature HDL particles can bind to specific receptors on hepatocytes (such as the apoE receptor), but the primary means of clearance of HDL from the blood is through its uptake by the scavenger receptor SR-B1. This receptor is present on many cell types, and once the HDL particle is bound to the receptor, its cholesterol and cholesterol esters are transferred into the cells. When depleted of cholesterol and its esters, the HDL particle dissociates from the SR-B1 receptor and reenters the circulation.', '56d46975-79b7-4571-9deb-23b06436b732': 'As previously mentioned, HDL plays a key role in the maturation of both chylomicrons and VLDL. First, HDL transfers apoE and apoCII to chylomicrons and to VLDL. The apoCII stimulates the degradation of the TAGs of chylomicrons and VLDL by activating LPL. After digestion of the chylomicrons and the VLDL TAGs, apoE and apoCII are transferred back to HDL.', 'b19d98b4-f02a-45e2-bb8e-082c4b819299': 'Another key interaction HDL has with VLDL allows for the redistribution of cholesterol between the two lipoproteins. When HDL obtains free cholesterol from cell membranes, HDL either transports the free cholesterol and cholesterol esters directly to the liver or it can exchange its cholesterol for TAGs in an interaction with VLDL. The cholesterol esterase transfer protein (CETP) resides in circulation and exchanges TAGs from VLDLs with cholesterol-esters from HDL. The greater the concentration of triacylglycerol-rich lipoproteins in the blood, the greater the rate of these exchanges. The CETP exchange pathway may partially explain the observation that whenever triacylglycerol-rich lipoproteins are present in the blood in high concentrations, the amount of cholesterol reaching the liver via cholesterol-enriched VLDL and VLDL remnants increases (figure 6.10), and is consistent with a proportional reduction in the total amount of cholesterol and cholesterol esters that are transferred directly to the liver via HDL.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.10,cell_bio/images/Figure 6.10.jpg,Figure 6.10: Interaction of chylomicrons and VLDL with HDL in circulation.,"HDLs can also be generated through budding of apoA from chylomicrons and VLDL particles or from free apoAI, which may be shed from other circulating lipoproteins. In this case, the apoAI acquires cholesterol and phospholipids from other lipoproteins and cell membranes, forming a nascent-like HDL particle within the circulation (figure 6.10).","{'dc9e84b3-c161-4992-8d11-23080026ca9f': 'The primary function of high-density lipoprotein (HDL) is to transport excess cholesterol obtained from peripheral tissues to the liver. HDL also has other roles integral to lipid transport such as exchanging proteins and lipids with chylomicrons and VLDL. HDL particles can be created by several mechanisms, however, nascent HDLs are primarily secreted from the liver and intestine as a relatively small particles whose shell, like that of other lipoproteins, contains phospholipids, free cholesterol, and a variety of apoproteins, specifically apoAI, apoAII, apoCI, and apoCII. Very low levels of triacylglycerols or cholesterol esters are found in the hollow core of this early, or nascent, version of HDL.', 'dad1f10e-9b0f-4a5e-8937-a872f4bc7524': 'HDLs can also be generated through budding of apoA from chylomicrons and VLDL particles or from free apoAI, which may be shed from other circulating lipoproteins. In this case, the apoAI acquires cholesterol and phospholipids from other lipoproteins and cell membranes, forming a nascent-like HDL particle within the circulation (figure 6.10).', '6b8c0c52-ebfd-41fb-abfc-2009813205ed': 'In the process of maturation, the nascent HDL particles accumulate phospholipids and cholesterol from cells lining the blood vessels. As the central hollow core of nascent HDL progressively fills with cholesterol esters, HDL takes on a more globular shape to eventually form the mature HDL particle. A major benefit of HDL particles derives from their ability to remove cholesterol from cholesterol-laden cells and to return the cholesterol to the liver, a process known as reverse cholesterol transport. This is particularly beneficial in vascular tissue; by reducing cellular cholesterol levels in the subintimal space, the likelihood that foam cells (lipid-laden macrophages that engulf oxidized LDL cholesterol) will form within the blood vessel wall is reduced.', '72a76514-97d2-4758-b87f-7f78d35977d4': 'Reverse cholesterol transport requires a movement of cholesterol from cellular stores to the lipoprotein particle. Cells contain the protein ABCA1 (ATP-binding cassette protein 1) that uses ATP hydrolysis to move cholesterol from the inner leaflet of the membrane to the outer leaflet. Once the cholesterol has reached the outer membrane leaflet, the HDL particle can accept it. To trap the cholesterol within the HDL core, the HDL particle acquires the enzyme lecithin-cholesterol acyltransferase (LCAT) from the circulation (figure 6.10). LCAT catalyzes the transfer of a fatty acid from the 2-position of lecithin (phosphatidylcholine) in the phospholipid shell of the particle to the 3-hydroxyl group of cholesterol, forming a cholesterol ester. The cholesterol esters form the core of the HDL particle and are\xa0no longer free to return to the cell.', 'e9abdebf-773e-4179-bf7b-20f6fe7cedfd': 'Mature HDL particles can bind to specific receptors on hepatocytes (such as the apoE receptor), but the primary means of clearance of HDL from the blood is through its uptake by the scavenger receptor SR-B1. This receptor is present on many cell types, and once the HDL particle is bound to the receptor, its cholesterol and cholesterol esters are transferred into the cells. When depleted of cholesterol and its esters, the HDL particle dissociates from the SR-B1 receptor and reenters the circulation.', '56d46975-79b7-4571-9deb-23b06436b732': 'As previously mentioned, HDL plays a key role in the maturation of both chylomicrons and VLDL. First, HDL transfers apoE and apoCII to chylomicrons and to VLDL. The apoCII stimulates the degradation of the TAGs of chylomicrons and VLDL by activating LPL. After digestion of the chylomicrons and the VLDL TAGs, apoE and apoCII are transferred back to HDL.', 'b19d98b4-f02a-45e2-bb8e-082c4b819299': 'Another key interaction HDL has with VLDL allows for the redistribution of cholesterol between the two lipoproteins. When HDL obtains free cholesterol from cell membranes, HDL either transports the free cholesterol and cholesterol esters directly to the liver or it can exchange its cholesterol for TAGs in an interaction with VLDL. The cholesterol esterase transfer protein (CETP) resides in circulation and exchanges TAGs from VLDLs with cholesterol-esters from HDL. The greater the concentration of triacylglycerol-rich lipoproteins in the blood, the greater the rate of these exchanges. The CETP exchange pathway may partially explain the observation that whenever triacylglycerol-rich lipoproteins are present in the blood in high concentrations, the amount of cholesterol reaching the liver via cholesterol-enriched VLDL and VLDL remnants increases (figure 6.10), and is consistent with a proportional reduction in the total amount of cholesterol and cholesterol esters that are transferred directly to the liver via HDL.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.10,cell_bio/images/Figure 6.10.jpg,Figure 6.10: Interaction of chylomicrons and VLDL with HDL in circulation.,"HDLs can also be generated through budding of apoA from chylomicrons and VLDL particles or from free apoAI, which may be shed from other circulating lipoproteins. In this case, the apoAI acquires cholesterol and phospholipids from other lipoproteins and cell membranes, forming a nascent-like HDL particle within the circulation (figure 6.10).","{'dc9e84b3-c161-4992-8d11-23080026ca9f': 'The primary function of high-density lipoprotein (HDL) is to transport excess cholesterol obtained from peripheral tissues to the liver. HDL also has other roles integral to lipid transport such as exchanging proteins and lipids with chylomicrons and VLDL. HDL particles can be created by several mechanisms, however, nascent HDLs are primarily secreted from the liver and intestine as a relatively small particles whose shell, like that of other lipoproteins, contains phospholipids, free cholesterol, and a variety of apoproteins, specifically apoAI, apoAII, apoCI, and apoCII. Very low levels of triacylglycerols or cholesterol esters are found in the hollow core of this early, or nascent, version of HDL.', 'dad1f10e-9b0f-4a5e-8937-a872f4bc7524': 'HDLs can also be generated through budding of apoA from chylomicrons and VLDL particles or from free apoAI, which may be shed from other circulating lipoproteins. In this case, the apoAI acquires cholesterol and phospholipids from other lipoproteins and cell membranes, forming a nascent-like HDL particle within the circulation (figure 6.10).', '6b8c0c52-ebfd-41fb-abfc-2009813205ed': 'In the process of maturation, the nascent HDL particles accumulate phospholipids and cholesterol from cells lining the blood vessels. As the central hollow core of nascent HDL progressively fills with cholesterol esters, HDL takes on a more globular shape to eventually form the mature HDL particle. A major benefit of HDL particles derives from their ability to remove cholesterol from cholesterol-laden cells and to return the cholesterol to the liver, a process known as reverse cholesterol transport. This is particularly beneficial in vascular tissue; by reducing cellular cholesterol levels in the subintimal space, the likelihood that foam cells (lipid-laden macrophages that engulf oxidized LDL cholesterol) will form within the blood vessel wall is reduced.', '72a76514-97d2-4758-b87f-7f78d35977d4': 'Reverse cholesterol transport requires a movement of cholesterol from cellular stores to the lipoprotein particle. Cells contain the protein ABCA1 (ATP-binding cassette protein 1) that uses ATP hydrolysis to move cholesterol from the inner leaflet of the membrane to the outer leaflet. Once the cholesterol has reached the outer membrane leaflet, the HDL particle can accept it. To trap the cholesterol within the HDL core, the HDL particle acquires the enzyme lecithin-cholesterol acyltransferase (LCAT) from the circulation (figure 6.10). LCAT catalyzes the transfer of a fatty acid from the 2-position of lecithin (phosphatidylcholine) in the phospholipid shell of the particle to the 3-hydroxyl group of cholesterol, forming a cholesterol ester. The cholesterol esters form the core of the HDL particle and are\xa0no longer free to return to the cell.', 'e9abdebf-773e-4179-bf7b-20f6fe7cedfd': 'Mature HDL particles can bind to specific receptors on hepatocytes (such as the apoE receptor), but the primary means of clearance of HDL from the blood is through its uptake by the scavenger receptor SR-B1. This receptor is present on many cell types, and once the HDL particle is bound to the receptor, its cholesterol and cholesterol esters are transferred into the cells. When depleted of cholesterol and its esters, the HDL particle dissociates from the SR-B1 receptor and reenters the circulation.', '56d46975-79b7-4571-9deb-23b06436b732': 'As previously mentioned, HDL plays a key role in the maturation of both chylomicrons and VLDL. First, HDL transfers apoE and apoCII to chylomicrons and to VLDL. The apoCII stimulates the degradation of the TAGs of chylomicrons and VLDL by activating LPL. After digestion of the chylomicrons and the VLDL TAGs, apoE and apoCII are transferred back to HDL.', 'b19d98b4-f02a-45e2-bb8e-082c4b819299': 'Another key interaction HDL has with VLDL allows for the redistribution of cholesterol between the two lipoproteins. When HDL obtains free cholesterol from cell membranes, HDL either transports the free cholesterol and cholesterol esters directly to the liver or it can exchange its cholesterol for TAGs in an interaction with VLDL. The cholesterol esterase transfer protein (CETP) resides in circulation and exchanges TAGs from VLDLs with cholesterol-esters from HDL. The greater the concentration of triacylglycerol-rich lipoproteins in the blood, the greater the rate of these exchanges. The CETP exchange pathway may partially explain the observation that whenever triacylglycerol-rich lipoproteins are present in the blood in high concentrations, the amount of cholesterol reaching the liver via cholesterol-enriched VLDL and VLDL remnants increases (figure 6.10), and is consistent with a proportional reduction in the total amount of cholesterol and cholesterol esters that are transferred directly to the liver via HDL.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.11,cell_bio/images/Figure 6.11.jpg,Figure 6.11: Uptake of LDL and regulation of cholesterol synthesis.,"Much like the conversion of chylomicrons to chylomicron remnants, LPL converts VLDL to an intermediate-density lipoprotein (IDL). IDLs, having relatively low TAG content, are taken up by the liver through endocytosis, and degraded lysosomes as discussed above. IDL may also be converted to low-density lipoprotein (LDL) by further digestion of TAGs. Endocytosis of LDL occurs in peripheral tissues (and the liver) and is the major means of cholesterol transport and delivery to peripheral tissues. LDLs taken up by peripheral tissues will help increase the amount of intracellular cholesterol and therefore influence the regulation of HMG-CoA reductase (figure 6.11).","{'a2a785be-d3f0-4ec2-bd4f-1ba416acea3b': 'Much like the conversion of chylomicrons to chylomicron remnants, LPL converts VLDL to an intermediate-density lipoprotein (IDL). IDLs, having relatively low TAG content, are taken up by the liver through endocytosis, and degraded lysosomes as discussed above. IDL may also be converted to low-density lipoprotein (LDL) by further digestion of TAGs. Endocytosis of LDL occurs in peripheral tissues (and the liver) and is the major means of cholesterol transport and delivery to peripheral tissues. LDLs taken up by peripheral tissues will help increase the amount of intracellular cholesterol and therefore influence the regulation of HMG-CoA reductase (figure 6.11).', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.6,cell_bio/images/Figure 6.6.jpg,Figure 6.6: Overview of lipoprotein size and structure.,"As such, a transport system for distribution of major lipids is in place to aid in the movement of these compounds. This system involves the family of lipoproteins, which have distinct roles in carrying dietary lipids, lipids synthesized through de novo mechanism in the liver, and for reverse cholesterol transport (figure 6.6).","{'1e1074ac-ef70-43ce-b84d-7d0f9ba0e939': 'As such, a transport system for distribution of major lipids is in place to aid in the movement of these compounds. This system involves the family of lipoproteins, which have distinct roles in carrying dietary lipids, lipids synthesized through de novo mechanism in the liver, and for reverse cholesterol transport (figure 6.6).', '6e690769-0660-48bf-a4ff-78208ea290a8': 'In addition to the lipid components of lipoproteins, they contain protein components termed apoproteins. The complement of apoproteins on each lipoprotein is unique and is a distinguishing characteristic of each family of lipoproteins. The apoproteins (“apo” describes the protein within the shell of the particle in its lipid-free form) not only add to the hydrophilicity and structural stability of the particle, but they have other functions as well: (1) They activate certain enzymes required for normal lipoprotein metabolism, and (2) they act as ligands on the surface of the lipoprotein that target specific receptors on peripheral tissues that require lipoprotein delivery for their innate cellular functions.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.7,cell_bio/images/Figure 6.7.jpg,Figure 6.7: Transport of dietary lipids via chylomicrons.,"Fatty acids, which are stored as TAGs, serve as fuels, providing the body with its major source of energy. TAGs are the major dietary lipids and are digested in the lumen of the intestine. The initial digestive products, free fatty acids and 2-monoacylglycerol, are reconverted to TAGs in intestinal epithelial cells, packaged in lipoproteins known as chylomicrons, and secreted into the lymph (figure 6.7).","{'19e4374e-a9e9-4532-8402-33b92129522a': 'Fatty acids, which are stored as TAGs, serve as fuels, providing the body with its major source of energy. TAGs are the major dietary lipids and are digested in the lumen of the intestine. The initial digestive products, free fatty acids and 2-monoacylglycerol, are reconverted to TAGs in intestinal epithelial cells, packaged in lipoproteins known as chylomicrons, and secreted into the lymph (figure 6.7).', '61f7c54a-6611-483c-81ff-6f65a3d6b334': 'Chylomicrons are the largest lipoproteins and contain cholesterol and fat-soluble vitamins, in addition to their major component, dietary TAGs. The major apoprotein associated with chylomicrons as they leave the intestinal cells is ApoB-48. (The B-48 apoprotein is structurally and genetically related to the B-100 apoprotein synthesized in the liver that serves as a major protein of VLDL.)\xa0Microsomal transfer protein (MTP) aids in the loading of apoB-48 protein onto the chylomicron before the nascent chylomicron is secreted. Nascent chylomicrons are secreted by the intestinal epithelial cells into the chyle of the lymphatic system and enter the blood through the thoracic duct. Nascent chylomicrons begin to enter the blood within one to two hours after the start of a meal; as the meal is digested and absorbed, they continue to enter the blood for many hours. Chylomicron maturation occurs in circulation as they accept additional apoproteins from high-density lipoprotein (HDL) (figures 6.7 and 6.10).', '1fb9aa77-009e-4ae1-97dc-ae12f1e692b5': 'HDL predominantly transfers apoproteins E and CII to the nascent chylomicrons. ApoE is recognized by membrane receptors, and this interaction allows apoE-bearing lipoproteins to enter these cells by endocytosis; once inside the cell the particle is broken down through a lysosomal-mediated process. ApoCII acts as an activator of lipoprotein lipase (LPL), the enzyme on capillary endothelial cells, which digests the TAGs of the chylomicrons and VLDLs in the blood.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.8,cell_bio/images/Figure 6.8.jpg,Figure 6.8: Transport of TAGs from de novo synthesis using VLDL.,"Very low-density lipoprotein (VLDL) is produced in the liver, mainly from lipogenesis. Lipogenesis is an insulin-stimulated process through which excess glucose is converted to fatty acids (section 4.4), which are subsequently esterified to glycerol to form TAGs. TAGs produced in the smooth endoplasmic reticulum of the liver are packaged with cholesterol, phospholipids, and proteins (synthesized in the rough endoplasmic reticulum) to form VLDLs. Apart from their initial origin, VLDLs and chylomicrons are very similar with respect to maturation and activity. The VLDL particles acquire apoB-100 through an MTP-mediated reaction before being released into circulation. Within circulation, VLDLs also interact with HDL and acquire ApoCII and ApoE (figure 6.8). Like chylomicrons, VLDLs are also hydrolyzed by lipoprotein lipase (LPL), and the released fatty acids can be taken up by muscle and other tissues to be oxidized. After a meal, these fatty acids are also taken up by adipose tissue and stored as TAGs. In summary, the process of dietary versus de novo lipid transport has many parallels, which are compared in figure 6.9.","{'84b462ad-96d0-472f-8da4-c09a5ab9a59a': 'Very low-density lipoprotein (VLDL) is produced in the liver, mainly from lipogenesis. Lipogenesis is an insulin-stimulated process through which excess glucose is converted to fatty acids (section 4.4), which are subsequently esterified to glycerol to form TAGs. TAGs produced in the smooth endoplasmic reticulum of the liver are packaged with cholesterol, phospholipids, and proteins (synthesized in the rough endoplasmic reticulum) to form VLDLs. Apart from their initial origin, VLDLs and chylomicrons are very similar with respect to maturation and activity. The VLDL particles acquire apoB-100 through an MTP-mediated reaction before being released into circulation. Within circulation, VLDLs also interact with HDL and acquire ApoCII and ApoE (figure 6.8). Like chylomicrons, VLDLs are also hydrolyzed by lipoprotein lipase (LPL), and the released fatty acids can be taken up by muscle and other tissues to be oxidized. After a meal, these fatty acids are also taken up by adipose tissue and stored as TAGs. In summary, the process of dietary versus\xa0de novo lipid transport has many parallels, which are compared in figure 6.9.', 'a7832ccd-7df7-4aa2-8c23-274080dc5d9e': 'Although VLDLs and chylomicrons have similar roles in the cell, it is important to keep them distinct. The comparison between the transport of exogenous lipids and endogenous lipids is illustrated in figure 6.9. Because the fatty acids stored in adipose tissue come both from chylomicrons and VLDL, we produce our major fat stores both from dietary fat (which is transported by chylomicrons) and dietary sugar (which can be synthesized into TAGs and packaged into VLDL). An excess of dietary protein also can be used to produce the fatty acids for VLDL synthesis. Clinically, measured triacylglycerols (under fasting conditions) will largely reflect the VLDL contribution.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.10,cell_bio/images/Figure 6.10.jpg,Figure 6.10: Interaction of chylomicrons and VLDL with HDL in circulation.,"HDLs can also be generated through budding of apoA from chylomicrons and VLDL particles or from free apoAI, which may be shed from other circulating lipoproteins. In this case, the apoAI acquires cholesterol and phospholipids from other lipoproteins and cell membranes, forming a nascent-like HDL particle within the circulation (figure 6.10).","{'dc9e84b3-c161-4992-8d11-23080026ca9f': 'The primary function of high-density lipoprotein (HDL) is to transport excess cholesterol obtained from peripheral tissues to the liver. HDL also has other roles integral to lipid transport such as exchanging proteins and lipids with chylomicrons and VLDL. HDL particles can be created by several mechanisms, however, nascent HDLs are primarily secreted from the liver and intestine as a relatively small particles whose shell, like that of other lipoproteins, contains phospholipids, free cholesterol, and a variety of apoproteins, specifically apoAI, apoAII, apoCI, and apoCII. Very low levels of triacylglycerols or cholesterol esters are found in the hollow core of this early, or nascent, version of HDL.', 'dad1f10e-9b0f-4a5e-8937-a872f4bc7524': 'HDLs can also be generated through budding of apoA from chylomicrons and VLDL particles or from free apoAI, which may be shed from other circulating lipoproteins. In this case, the apoAI acquires cholesterol and phospholipids from other lipoproteins and cell membranes, forming a nascent-like HDL particle within the circulation (figure 6.10).', '6b8c0c52-ebfd-41fb-abfc-2009813205ed': 'In the process of maturation, the nascent HDL particles accumulate phospholipids and cholesterol from cells lining the blood vessels. As the central hollow core of nascent HDL progressively fills with cholesterol esters, HDL takes on a more globular shape to eventually form the mature HDL particle. A major benefit of HDL particles derives from their ability to remove cholesterol from cholesterol-laden cells and to return the cholesterol to the liver, a process known as reverse cholesterol transport. This is particularly beneficial in vascular tissue; by reducing cellular cholesterol levels in the subintimal space, the likelihood that foam cells (lipid-laden macrophages that engulf oxidized LDL cholesterol) will form within the blood vessel wall is reduced.', '72a76514-97d2-4758-b87f-7f78d35977d4': 'Reverse cholesterol transport requires a movement of cholesterol from cellular stores to the lipoprotein particle. Cells contain the protein ABCA1 (ATP-binding cassette protein 1) that uses ATP hydrolysis to move cholesterol from the inner leaflet of the membrane to the outer leaflet. Once the cholesterol has reached the outer membrane leaflet, the HDL particle can accept it. To trap the cholesterol within the HDL core, the HDL particle acquires the enzyme lecithin-cholesterol acyltransferase (LCAT) from the circulation (figure 6.10). LCAT catalyzes the transfer of a fatty acid from the 2-position of lecithin (phosphatidylcholine) in the phospholipid shell of the particle to the 3-hydroxyl group of cholesterol, forming a cholesterol ester. The cholesterol esters form the core of the HDL particle and are\xa0no longer free to return to the cell.', 'e9abdebf-773e-4179-bf7b-20f6fe7cedfd': 'Mature HDL particles can bind to specific receptors on hepatocytes (such as the apoE receptor), but the primary means of clearance of HDL from the blood is through its uptake by the scavenger receptor SR-B1. This receptor is present on many cell types, and once the HDL particle is bound to the receptor, its cholesterol and cholesterol esters are transferred into the cells. When depleted of cholesterol and its esters, the HDL particle dissociates from the SR-B1 receptor and reenters the circulation.', '56d46975-79b7-4571-9deb-23b06436b732': 'As previously mentioned, HDL plays a key role in the maturation of both chylomicrons and VLDL. First, HDL transfers apoE and apoCII to chylomicrons and to VLDL. The apoCII stimulates the degradation of the TAGs of chylomicrons and VLDL by activating LPL. After digestion of the chylomicrons and the VLDL TAGs, apoE and apoCII are transferred back to HDL.', 'b19d98b4-f02a-45e2-bb8e-082c4b819299': 'Another key interaction HDL has with VLDL allows for the redistribution of cholesterol between the two lipoproteins. When HDL obtains free cholesterol from cell membranes, HDL either transports the free cholesterol and cholesterol esters directly to the liver or it can exchange its cholesterol for TAGs in an interaction with VLDL. The cholesterol esterase transfer protein (CETP) resides in circulation and exchanges TAGs from VLDLs with cholesterol-esters from HDL. The greater the concentration of triacylglycerol-rich lipoproteins in the blood, the greater the rate of these exchanges. The CETP exchange pathway may partially explain the observation that whenever triacylglycerol-rich lipoproteins are present in the blood in high concentrations, the amount of cholesterol reaching the liver via cholesterol-enriched VLDL and VLDL remnants increases (figure 6.10), and is consistent with a proportional reduction in the total amount of cholesterol and cholesterol esters that are transferred directly to the liver via HDL.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.9,cell_bio/images/Figure 6.9.jpg,Figure 6.9: Comparison of the role of chylomicrons and VLDLs in lipid transport.,"Although VLDLs and chylomicrons have similar roles in the cell, it is important to keep them distinct. The comparison between the transport of exogenous lipids and endogenous lipids is illustrated in figure 6.9. Because the fatty acids stored in adipose tissue come both from chylomicrons and VLDL, we produce our major fat stores both from dietary fat (which is transported by chylomicrons) and dietary sugar (which can be synthesized into TAGs and packaged into VLDL). An excess of dietary protein also can be used to produce the fatty acids for VLDL synthesis. Clinically, measured triacylglycerols (under fasting conditions) will largely reflect the VLDL contribution.","{'84b462ad-96d0-472f-8da4-c09a5ab9a59a': 'Very low-density lipoprotein (VLDL) is produced in the liver, mainly from lipogenesis. Lipogenesis is an insulin-stimulated process through which excess glucose is converted to fatty acids (section 4.4), which are subsequently esterified to glycerol to form TAGs. TAGs produced in the smooth endoplasmic reticulum of the liver are packaged with cholesterol, phospholipids, and proteins (synthesized in the rough endoplasmic reticulum) to form VLDLs. Apart from their initial origin, VLDLs and chylomicrons are very similar with respect to maturation and activity. The VLDL particles acquire apoB-100 through an MTP-mediated reaction before being released into circulation. Within circulation, VLDLs also interact with HDL and acquire ApoCII and ApoE (figure 6.8). Like chylomicrons, VLDLs are also hydrolyzed by lipoprotein lipase (LPL), and the released fatty acids can be taken up by muscle and other tissues to be oxidized. After a meal, these fatty acids are also taken up by adipose tissue and stored as TAGs. In summary, the process of dietary versus\xa0de novo lipid transport has many parallels, which are compared in figure 6.9.', 'a7832ccd-7df7-4aa2-8c23-274080dc5d9e': 'Although VLDLs and chylomicrons have similar roles in the cell, it is important to keep them distinct. The comparison between the transport of exogenous lipids and endogenous lipids is illustrated in figure 6.9. Because the fatty acids stored in adipose tissue come both from chylomicrons and VLDL, we produce our major fat stores both from dietary fat (which is transported by chylomicrons) and dietary sugar (which can be synthesized into TAGs and packaged into VLDL). An excess of dietary protein also can be used to produce the fatty acids for VLDL synthesis. Clinically, measured triacylglycerols (under fasting conditions) will largely reflect the VLDL contribution.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 6.2,cell_bio/images/Figure 6.2.jpg,Figure 6.2: Cholesterol synthetic pathway.,"Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four stages (figure 6.2); however, only the first stage is regulated and will be focused on here.","{'15599fc7-273f-4c10-92db-e3d5ee5909e3': 'Synthesis of dTMP for DNA synthesis is the rate-limiting step for the replication process, and therefore disruption of this conversion is very effective at reducing cellular proliferation. Inhibition of thymidylate synthase by 5-fluorouracil (5-FU) is a common anticancer treatment. 5-FU functions as a thymine analog and will irreversibly bind the enzyme. Similarly, methotrexate is an inhibitor of dihyrofolate reductase (DHFR), which is part of the folate cycle needed to reduce dihydrofolate to tetrahydrofolate. Inhibition of this process reduces substrate needed for the thymidylate synthase reaction and has a similar effect as inhibition of by 5-FU (figure 7.13).', 'd8321c1a-07c2-41d0-8b9c-01bfccd9083b': 'Table 7.2: Summary of pathway regulation.', '47657f91-15ef-4b6f-a069-5aec71d3c498': '7.2 References and resources', '0869898c-2cbd-4d9f-8f7f-f149e30c7855': 'Lieberman M, Peet A. Figure 7.4 Basic structure of nucleotides. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 216. Figure 12.3 Nucleoside and nucleotide structures displayed with ribose as the sugar. 2017. Chemical structure by Henry Jakubowski.', '2687100e-d1c9-4625-9b84-ea3b77ba33bd': 'Cholesterol synthesis takes place in the cytosol, and the acetyl-CoA needed can be obtained from several sources such as β-oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction (acetyl-CoA shuttled out of the mitochondria is in the form of citrate, which is cleaved into acetyl-CoA and pyruvate by citrate lyase). The process of cholesterol synthesis involves four\xa0stages (figure 6.2); however, only the first stage is regulated and will be focused on here.', '7f3cf870-f425-4323-aada-dc4aa9c9283b': 'The following highlights some of the key aspects of amino acid metabolism.', 'f236022a-c9d1-472f-8edc-3b69bba5ce8d': 'The hepatic cholesterol pool serves as a source of cholesterol for the synthesis of the relatively hydrophilic bile acids and their salts. These derivatives of cholesterol are effective detergents because they contain both polar and nonpolar regions. They are introduced into the biliary ducts of the liver. They are stored and concentrated in the gallbladder and later discharged into the gut in response to the ingestion of food. Finally, cholesterol is the precursor of all five classes of steroid hormones: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins. Cholesterol and steroid hormones are transported through the blood from their sites of synthesis to their target organs. Because of their hydrophobicity, they must be complexed with a serum protein. Serum albumin can act as a nonspecific carrier for the steroid hormones, but there are specific carriers as well (section 2.1).', '454c78e1-f270-4eac-afa0-a664cafea36c': '6.1 References and resources', 'f40832f7-1c5c-4c67-96db-cd371f00fb37': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 15: Metabolism of Dietary Lipids, Chapter 18: Cholesterol and Steroid Metabolism.', '81442bf1-bc27-4826-be31-285f6c5d112c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 92–94.', '4ae65743-884b-453d-a227-1102ad059aaa': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 29: Digestion and Transport of Dietary Lipids, Chapter 32: Cholesterol Absorption: Synthesis, Metabolism and Fate Section.', '3e1b3cbc-717d-4a3f-9998-2a56de7cd452': 'Lieberman M, Peet A. Figure 6.4 Regulation of cholesterol synthesis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 647. Figure 32.6 Regulation of 3-hydroxymethylglutryl coenzyme A (HMG-CoA reductase activity. 2017. Added squiggle by Made by Made from the Noun Project and ion channel by Léa Lortal from the Noun Project.', 'ca403ebf-f143-4273-b51b-9cad6f2683dc': '6.2 Lipid Transport', 'e9ad3c68-d453-4393-a928-2c51370d5008': 'Most of the lipids found in the body fall into the categories of fatty acids and triacylglycerols (TAGs); glycerophospholipids and sphingolipids; eicosanoids; cholesterol, bile salts, and steroid hormones; and fat-soluble vitamins. These lipids have very diverse chemical structures and functions. However, they are related by a common property, their relative insolubility in water.', '48095600-24b8-4c72-88aa-3556a7c6dae7': 'As VLDLs mature to LDLs, these lipoproteins can be taken up through an interaction of the ApoB100 with the LDL receptors on the cell surface. The receptors for LDL are found in clathrin-coated pits within the cell membrane of the target cells. Upon receptor ligand interaction, the plasma membrane in the vicinity of the receptor‒LDL complex invaginates and fuses to form an endocytic vesicle. These vesicles then fuse with lysosomes, and the cholesterol esters of LDL are hydrolyzed to form free cholesterol, which is rapidly re-esterified through the action of ACAT. This rapid re-esterification is necessary to avoid the damaging effect of high levels of free cholesterol on cellular membranes.', '25f6199d-ded6-4bcd-9265-7857911ad5f1': 'The synthesis of the LDL receptor itself is regulated by feedback inhibition as intracellular levels of cholesterol increase. One probable mechanism for this feedback regulation involves one or more of the SREBPs described earlier. These proteins or the cofactors that are required for the full expression of genes that code for the LDL receptor are also capable of sensing the concentration of cholesterol (and its derivatives) within the cell. When sterol levels are high, the process that leads to the binding of the SREBP to the SRE of these genes is suppressed. The rate of synthesis from mRNA for the LDL receptor is reduced under these circumstances. This, in turn, appropriately reduces the amount of cholesterol that can enter these cholesterol-rich cells by receptor-mediated endocytosis (down-regulation of receptor synthesis). When the intracellular levels of cholesterol decrease, these processes are reversed, and cells act to increase their cholesterol levels. Both synthesis of cholesterol from acetyl-CoA and synthesis of LDL receptors are stimulated. An increased number of receptors (up-regulation of receptor synthesis) results in an increased uptake of LDL cholesterol from the blood, with a subsequent reduction of LDL cholesterol levels. At the same time, the cellular cholesterol pool is replenished (figure 6.11).', 'fed3baf8-45be-46ab-a2d5-77e9bf2047d8': '6.2 References and resources', 'c5adc32d-bfb0-4914-814b-f61b9e904759': 'Ferrier D. Figure 6.6 Overview of lipoprotein size and structure. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 227. Figure 18.13 Plasma lipoprotein particles exhibit a range of sizes and densities, and typical values are shown. 2017.', 'f80ed7ae-fc53-44b7-b6ed-655d6158696c': 'Ferrier D. Figure 6.11 Uptake of LDL and regulation of cholesterol synthesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 233. Figure 18.20 Cellular uptake and degradation of low-density lipoprotein (LDL) particles. 2017. Added squiggle by Made by Made from the Noun Project.', '10da76d4-1616-4c77-a52d-4434a0b73c1d': 'Lieberman M, Peet A. Figure 6.7 Transport of dietary lipids via chylomicrons. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 601. Figure 29.11 Fate of chylomicrons. 2017. Added Liver by Liam Mitchell from the Noun Project, Muscle by Laymik from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'cceb5fdc-50d2-47d7-9f23-20f78d5bd0d1': 'Lieberman M, Peet A. Figure 6.8 Transport of TAGs from de novo synthesis using VLDL. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 680. Figure 32.12 Fate of very-low-desnity lipoprteins (VLDL). 2017. Added macrophage by Léa Lortal from the Noun Project, Liver by Liam Mitchell from the Noun Project, and red blood cells by Lucas Helle from the Noun Project.', 'e7131b43-1fa8-4fb3-ad35-9a3b8ec0af3b': 'Lieberman M, Peet A. Figure 6.10 Interaction of chylomicrons and VLDL with HDL in circulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 683. Figure 32.15 Functions and fate of high-density lipoprotein (HDL). 2017. Added Liver by Liam Mitchell from the Noun Project.', '0585668d-eb07-4c87-b748-39d6ce97ba63': 'Loscalzo J. Figure 6.9 Comparison of the role of chylomicrons and VLDLs in lipid transport. Adapted under Fair Use from Harrison’s Cardiovascular Medicine 2 ed. online. Figure 31.2 The exogenous and endogenous lipoprotein metabolic pathways. 2013. Added Small Intestine by PJ Witt from the Noun Project, Liver by Liam Mitchell from the Noun Project, and Muscle by Laymik from the Noun Project.'}"
Figure 5.1,cell_bio/images/Figure 5.1.jpg,Figure 5.1: Glucose production by glycogenolysis and gluconeogenesis.,"Gluconeogenesis and glycogenolysis are the two pathways essential for glucose homeostasis. Figure 5.1 illustrates the time frame and overlap of glycogenolysis and gluconeogenesis. These pathways are activated nearly simultaneously when the insulin to glucagon ratio becomes sufficiently reduced. Over time, the reliance on the pathways changes.","{'c47897ec-9681-4c6c-95b1-08fe4cfe0234': 'Glycogenolysis (see section 4.5)', 'be5d552c-0325-4f4a-bb11-c49abb636892': 'Gluconeogenesis and glycogenolysis are the two pathways essential for glucose homeostasis. Figure 5.1 illustrates the time frame and overlap of glycogenolysis and gluconeogenesis. These pathways are activated nearly simultaneously when the insulin to glucagon ratio becomes sufficiently reduced. Over time, the reliance on the pathways changes.', 'e3b226cb-1f77-4afc-815b-e7daab1dbe0d': 'Gluconeogenesis (GNG) is an anabolic pathway that produces glucose from lactate, glycerol, or glucogenic amino acids. This pathway is activated primarily in the liver during fasting and is coordinated with the catabolic pathways of β-oxidation and protein catabolism. The pathway follows the reverse of glycolysis with the exception of four unique enzymes, which overcome the irreversible steps of glycolysis (figure 5.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.2,cell_bio/images/Figure 5.2.jpg,Figure 5.2: Comparison of glycolysis and gluconeogenesis.,"Gluconeogenesis (GNG) is an anabolic pathway that produces glucose from lactate, glycerol, or glucogenic amino acids. This pathway is activated primarily in the liver during fasting and is coordinated with the catabolic pathways of β-oxidation and protein catabolism. The pathway follows the reverse of glycolysis with the exception of four unique enzymes, which overcome the irreversible steps of glycolysis (figure 5.2).","{'c47897ec-9681-4c6c-95b1-08fe4cfe0234': 'Glycogenolysis (see section 4.5)', 'be5d552c-0325-4f4a-bb11-c49abb636892': 'Gluconeogenesis and glycogenolysis are the two pathways essential for glucose homeostasis. Figure 5.1 illustrates the time frame and overlap of glycogenolysis and gluconeogenesis. These pathways are activated nearly simultaneously when the insulin to glucagon ratio becomes sufficiently reduced. Over time, the reliance on the pathways changes.', 'e3b226cb-1f77-4afc-815b-e7daab1dbe0d': 'Gluconeogenesis (GNG) is an anabolic pathway that produces glucose from lactate, glycerol, or glucogenic amino acids. This pathway is activated primarily in the liver during fasting and is coordinated with the catabolic pathways of β-oxidation and protein catabolism. The pathway follows the reverse of glycolysis with the exception of four unique enzymes, which overcome the irreversible steps of glycolysis (figure 5.2).', '977b4b53-5358-41f0-8d9f-4ff563e872f7': 'Gluconeogenesis is essentially the reverse of glycolysis with four\xa0key regulatory steps that allow the bypass of the three\xa0irreversible steps of glycolysis (figure 5.2). This initial step of GNG starts in the mitochondria using pyruvate carboxylase (figure 5.5). This enzyme converts pyruvate in the mitochondria to oxaloacetate and requires biotin as a cofactor. This enzyme is allosterically activated by acetyl-CoA. The OAA produced is reduced to malate, which is shuttled out of the mitochondria using the malate-aspartate shuttle. Once in the cytosol, the malate is oxidized back to OAA and decarboxylated by the enzyme phosphoenol carboxykinase (PEPCK) to generate phosphoenol pyruvate (figure 5.3). The combination of these two enzymes, pyruvate carboxylase and PEPCK, allows the cell to bypass the irreversible step catalyzed by pyruvate kinase.', '468dd3a5-1956-4116-8626-1ce68cda9a38': 'Once phosphoenol pyruvate (PEP) is synthesized, it will continue through the reverse process using the glycolytic enzymes until it reaches its next irreversible conversion.', '12c5c357-49fb-4f02-8d67-cf4e9a649d4b': 'As PEP continues through the reverse of glycolysis, fructose 1,6-bisphosphate is generated. To bypass the irreversible step catalyzed by phosphofructokinase 1 (PFK1) in glycolysis, the enzyme fructose 1,6-bisphosphatase (FBP1) is present and dephosphorylates fructose 1,6-bisphosphate to produce fructose 6-phosphate. This enzyme, FBP1, is inhibited by AMP and fructose 2,6-bisphosphate (figure 5.2).', 'a9b7cea1-4ae3-4760-b736-cbe9e0e7eaa4': 'Like glycolysis, there is an additional regulation here by the bifunctional enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase (figure 4.1). This bifunctional enzyme functions as a kinase in the fed state (PFK2) and generates fructose 2,6-bisphosphate that allosterically activates PFK1. In the fasted state the enzyme is phosphorylated by glucagon-activated protein kinase A, and this actives the phosphatase activity of the enzyme. The enzyme dephosphorylates fructose 2,6-bisphosphate and therefore reduces the allosteric activation of PFK1 facilitating the reverse reaction by fructose 1,6-bisphosphatase (figure 5.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.11,cell_bio/images/Figure 5.11.jpg,Figure 5.11: Overview of ketone body formation.,"The primary substrates for GNG are derived from glucogenic amino acids released through cortisol-mediated protein catabolism. In the fasted state, cortisol is elevated, and it supports fasted state pathways through the activation of protein catabolism — in the skeletal muscle — and by increasing the transcription of enzymes needed for gluconeogenesis (specifically phosphoenol carboxykinase (PEPCK)). As amino acids are released from the skeletal muscle, primarily as glutamine and alanine, they are taken up by the liver. In order to be used for glucose synthesis, they undergo transamination to generate a useful intermediate of the TCA cycle, predominantly α-ketoglutarate and pyruvate (see figures 5.3 and 5.10) . In the case of alanine, this can be transaminated to generate pyruvate. Glutamine will first be deaminated by glutaminase, and the remaining glutamate will be transaminated to form α-ketoglutarate (see figure 5.11). Both pyruvate and α-ketoglutarate will increase substrates in the TCA cycle, ultimately increasing the pool of available malate to be shuttled out of the mitochondria. It is through this process of protein catabolism and transamination that glucogenic amino acids contribute to the synthesis of oxaloacetate (OAA) needed for gluconeogenesis.","{'791a7b80-2845-490c-b751-394d6b7310e7': 'The primary substrates for GNG are derived from glucogenic amino acids released through cortisol-mediated protein catabolism. In the fasted state, cortisol is elevated, and it supports fasted state pathways through the activation of protein catabolism —\xa0in the skeletal muscle —\xa0and by increasing the transcription of enzymes needed for gluconeogenesis (specifically phosphoenol carboxykinase (PEPCK)). As amino acids are released from the skeletal muscle, primarily as glutamine and alanine, they are taken up by the liver. In order to be used for glucose synthesis, they undergo transamination to generate a useful intermediate of the TCA cycle, predominantly α-ketoglutarate and pyruvate (see figures 5.3 and 5.10) . In the case of alanine, this can be transaminated to generate pyruvate. Glutamine will first be deaminated by glutaminase, and the remaining glutamate will be transaminated to form α-ketoglutarate (see figure 5.11). Both pyruvate and α-ketoglutarate will increase substrates in the TCA cycle, ultimately increasing the pool of available malate to be shuttled out of the mitochondria. It is through this process of protein catabolism and transamination that glucogenic amino acids contribute to the synthesis of oxaloacetate (OAA) needed for gluconeogenesis.', '7592682d-cc74-44e6-8c22-01de8a817bb1': 'As mentioned above, the acetyl-CoA produced by β-oxidation is primarily used for ketogenesis — the synthesis of ketone bodies. Substrates for ketogenesis can also come from the oxidation of ketogenic amino acids. In the fasted state, the process of β-oxidation generates a significant amount of acetyl-CoA, and although some of this substrate can be oxidized in the TCA cycle, we need to consider the other metabolic processes occurring. First, the significant amount of NADH generated through β-oxidation reduces flux through the TCA cycle by decreasing the activity of both α-ketoglutarate dehydrogenase and isocitrate dehydrogenase. Second, the process of gluconeogenesis is occurring, and intermediates of the TCA cycle, specifically malate, are actively being moved out of the mitochondria. The combination of these two processes reduces the TCA cycle activity allowing for an accumulation of acetyl-CoA. As acetyl-CoA levels elevate in the mitochondria, this will drive the thiolase reaction to generate acetoacetyl-CoA from two acetyl-CoA molecules (figure 5.11).', 'e8b2c041-78e0-45e7-ba6c-31161566065c': 'This compound is the substrate for HMG-CoA synthase, which generates 3-hydroxy-3-methyl glutaryl-CoA (HMG-CoA). HMG-CoA is then accepted by HMG-CoA lyase where an acetyl-CoA group is removed to generate acetoacetate. Acetoacetate can either undergo spontaneous decarboxylation to acetone, which can be exhaled, or it can be reduced to β-hydroxybutyrate using NADH. Acetoacetate and β-hydroxybutyrate are the two primary ketone bodies in circulation, and the ratio of the two is dependent on levels of NADH (figure 5.11). These two ketone bodies can be used as fuel in most tissues with the exception of the liver, which lacks thiophorase, the enzyme needed to metabolize these substrates. Ketone oxidation is not a primary fuel source, as fatty acid oxidation is preferred, but it can supply energy to some peripheral tissues. The brain can also oxidize ketones but only under extreme situations, such as starvation states.', 'eec41915-2c09-4a80-94e9-742520e4e4d8': 'Table 5.2: Summary of pathway regulation.', '76872677-0281-4e4f-b803-3400ad732ead': '5.2 References and resources', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 5.3,cell_bio/images/Figure 5.3.jpg,Figure 5.3: Locations of amino acid and lactate entering gluconeogenesis as substrates for the pathway.,"Lactate is primarily produced through the Cori cycle or from anaerobic glucose oxidation. (Note: The Cori cycle, or lactic acid cycle, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscle or RBC travels to the liver and is converted to glucose. The glucose returns to the peripheral tissues and is metabolized back to lactate.) Once in the liver, lactate can be oxidized back to pyruvate through the reverse reaction catalyzed by lactate dehydrogenase (figure 5.3).","{'c827d3f2-88d2-4b93-9996-ea3bb4eb386e': 'Lactate is primarily produced through the Cori cycle or from anaerobic glucose oxidation. (Note: The Cori cycle, or lactic acid cycle, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscle or RBC travels to the liver and is converted to glucose. The glucose returns to the peripheral tissues and is metabolized back to lactate.)\xa0Once in the liver, lactate can be oxidized back to pyruvate through the reverse reaction catalyzed by lactate dehydrogenase (figure 5.3).', 'a1bd4d19-e758-479c-b85d-67408c03c539': 'Serum lactate levels may also be measured in conjunction with a complete metabolic panel. Serum lactate should be negligible under normal conditions, however, elevated lactate could be suggestive of excessive anaerobic metabolism, such as is the case in intense exercise or deficiency in oxygen transport caused by ischemic injury. This could also be caused by inappropriate diversion of substrate such as is the case in some enzymatic deficiencies (pyruvate dehydrogenase deficiency) or changes in NADH levels (figure 2.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', 'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 5.4,cell_bio/images/Figure 5.4.jpg,"Figure 5.4: Glycerol as a substrate for gluconeogenesis; after phosphorylation to glycerol 3-phosphate it can be converted to DHAP, which can enter directly into glycolysis.","When lipolysis is stimulated by epinephrine or glucagon, activation of hormone-sensitive lipase in the adipose allows for the hydrolysis of triacylglycerol into three free fatty acid chains and glycerol. The glycerol released into circulation will be taken up by the liver. Once in the liver it can be converted into dihydroxyacetone phosphate (DHAP), a glycolytic intermediate. This is an additional way in which carbons can be obtained for glucose synthesis (figure 5.4).","{'cc7d6716-b10f-4fb4-b3a9-06aa2d5b05dd': 'When lipolysis is stimulated by epinephrine or glucagon, activation of hormone-sensitive lipase in the adipose allows for the hydrolysis of triacylglycerol into three free fatty acid chains and glycerol. The glycerol released into circulation will be taken up by the liver. Once in the liver it can be converted into dihydroxyacetone phosphate (DHAP), a glycolytic intermediate. This is an additional way in which carbons can be obtained for glucose synthesis (figure 5.4).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.2,cell_bio/images/Figure 5.2.jpg,Figure 5.2: Comparison of glycolysis and gluconeogenesis.,"Gluconeogenesis (GNG) is an anabolic pathway that produces glucose from lactate, glycerol, or glucogenic amino acids. This pathway is activated primarily in the liver during fasting and is coordinated with the catabolic pathways of β-oxidation and protein catabolism. The pathway follows the reverse of glycolysis with the exception of four unique enzymes, which overcome the irreversible steps of glycolysis (figure 5.2).","{'c47897ec-9681-4c6c-95b1-08fe4cfe0234': 'Glycogenolysis (see section 4.5)', 'be5d552c-0325-4f4a-bb11-c49abb636892': 'Gluconeogenesis and glycogenolysis are the two pathways essential for glucose homeostasis. Figure 5.1 illustrates the time frame and overlap of glycogenolysis and gluconeogenesis. These pathways are activated nearly simultaneously when the insulin to glucagon ratio becomes sufficiently reduced. Over time, the reliance on the pathways changes.', 'e3b226cb-1f77-4afc-815b-e7daab1dbe0d': 'Gluconeogenesis (GNG) is an anabolic pathway that produces glucose from lactate, glycerol, or glucogenic amino acids. This pathway is activated primarily in the liver during fasting and is coordinated with the catabolic pathways of β-oxidation and protein catabolism. The pathway follows the reverse of glycolysis with the exception of four unique enzymes, which overcome the irreversible steps of glycolysis (figure 5.2).', '977b4b53-5358-41f0-8d9f-4ff563e872f7': 'Gluconeogenesis is essentially the reverse of glycolysis with four\xa0key regulatory steps that allow the bypass of the three\xa0irreversible steps of glycolysis (figure 5.2). This initial step of GNG starts in the mitochondria using pyruvate carboxylase (figure 5.5). This enzyme converts pyruvate in the mitochondria to oxaloacetate and requires biotin as a cofactor. This enzyme is allosterically activated by acetyl-CoA. The OAA produced is reduced to malate, which is shuttled out of the mitochondria using the malate-aspartate shuttle. Once in the cytosol, the malate is oxidized back to OAA and decarboxylated by the enzyme phosphoenol carboxykinase (PEPCK) to generate phosphoenol pyruvate (figure 5.3). The combination of these two enzymes, pyruvate carboxylase and PEPCK, allows the cell to bypass the irreversible step catalyzed by pyruvate kinase.', '468dd3a5-1956-4116-8626-1ce68cda9a38': 'Once phosphoenol pyruvate (PEP) is synthesized, it will continue through the reverse process using the glycolytic enzymes until it reaches its next irreversible conversion.', '12c5c357-49fb-4f02-8d67-cf4e9a649d4b': 'As PEP continues through the reverse of glycolysis, fructose 1,6-bisphosphate is generated. To bypass the irreversible step catalyzed by phosphofructokinase 1 (PFK1) in glycolysis, the enzyme fructose 1,6-bisphosphatase (FBP1) is present and dephosphorylates fructose 1,6-bisphosphate to produce fructose 6-phosphate. This enzyme, FBP1, is inhibited by AMP and fructose 2,6-bisphosphate (figure 5.2).', 'a9b7cea1-4ae3-4760-b736-cbe9e0e7eaa4': 'Like glycolysis, there is an additional regulation here by the bifunctional enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase (figure 4.1). This bifunctional enzyme functions as a kinase in the fed state (PFK2) and generates fructose 2,6-bisphosphate that allosterically activates PFK1. In the fasted state the enzyme is phosphorylated by glucagon-activated protein kinase A, and this actives the phosphatase activity of the enzyme. The enzyme dephosphorylates fructose 2,6-bisphosphate and therefore reduces the allosteric activation of PFK1 facilitating the reverse reaction by fructose 1,6-bisphosphatase (figure 5.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.2,cell_bio/images/Figure 5.2.jpg,Figure 5.2: Comparison of glycolysis and gluconeogenesis.,"Gluconeogenesis (GNG) is an anabolic pathway that produces glucose from lactate, glycerol, or glucogenic amino acids. This pathway is activated primarily in the liver during fasting and is coordinated with the catabolic pathways of β-oxidation and protein catabolism. The pathway follows the reverse of glycolysis with the exception of four unique enzymes, which overcome the irreversible steps of glycolysis (figure 5.2).","{'c47897ec-9681-4c6c-95b1-08fe4cfe0234': 'Glycogenolysis (see section 4.5)', 'be5d552c-0325-4f4a-bb11-c49abb636892': 'Gluconeogenesis and glycogenolysis are the two pathways essential for glucose homeostasis. Figure 5.1 illustrates the time frame and overlap of glycogenolysis and gluconeogenesis. These pathways are activated nearly simultaneously when the insulin to glucagon ratio becomes sufficiently reduced. Over time, the reliance on the pathways changes.', 'e3b226cb-1f77-4afc-815b-e7daab1dbe0d': 'Gluconeogenesis (GNG) is an anabolic pathway that produces glucose from lactate, glycerol, or glucogenic amino acids. This pathway is activated primarily in the liver during fasting and is coordinated with the catabolic pathways of β-oxidation and protein catabolism. The pathway follows the reverse of glycolysis with the exception of four unique enzymes, which overcome the irreversible steps of glycolysis (figure 5.2).', '977b4b53-5358-41f0-8d9f-4ff563e872f7': 'Gluconeogenesis is essentially the reverse of glycolysis with four\xa0key regulatory steps that allow the bypass of the three\xa0irreversible steps of glycolysis (figure 5.2). This initial step of GNG starts in the mitochondria using pyruvate carboxylase (figure 5.5). This enzyme converts pyruvate in the mitochondria to oxaloacetate and requires biotin as a cofactor. This enzyme is allosterically activated by acetyl-CoA. The OAA produced is reduced to malate, which is shuttled out of the mitochondria using the malate-aspartate shuttle. Once in the cytosol, the malate is oxidized back to OAA and decarboxylated by the enzyme phosphoenol carboxykinase (PEPCK) to generate phosphoenol pyruvate (figure 5.3). The combination of these two enzymes, pyruvate carboxylase and PEPCK, allows the cell to bypass the irreversible step catalyzed by pyruvate kinase.', '468dd3a5-1956-4116-8626-1ce68cda9a38': 'Once phosphoenol pyruvate (PEP) is synthesized, it will continue through the reverse process using the glycolytic enzymes until it reaches its next irreversible conversion.', '12c5c357-49fb-4f02-8d67-cf4e9a649d4b': 'As PEP continues through the reverse of glycolysis, fructose 1,6-bisphosphate is generated. To bypass the irreversible step catalyzed by phosphofructokinase 1 (PFK1) in glycolysis, the enzyme fructose 1,6-bisphosphatase (FBP1) is present and dephosphorylates fructose 1,6-bisphosphate to produce fructose 6-phosphate. This enzyme, FBP1, is inhibited by AMP and fructose 2,6-bisphosphate (figure 5.2).', 'a9b7cea1-4ae3-4760-b736-cbe9e0e7eaa4': 'Like glycolysis, there is an additional regulation here by the bifunctional enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase (figure 4.1). This bifunctional enzyme functions as a kinase in the fed state (PFK2) and generates fructose 2,6-bisphosphate that allosterically activates PFK1. In the fasted state the enzyme is phosphorylated by glucagon-activated protein kinase A, and this actives the phosphatase activity of the enzyme. The enzyme dephosphorylates fructose 2,6-bisphosphate and therefore reduces the allosteric activation of PFK1 facilitating the reverse reaction by fructose 1,6-bisphosphatase (figure 5.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.1,cell_bio/images/Figure 4.1.jpg,"Figure 4.1: Summary of glycolysis. The three regulated steps of the process will be the focus, and those are catalyzed by the enzymes glucokinase/hexokinase, phosphofructokinase 1 (PFK1), and pyruvate kinase. All other steps in glycolysis are reversible (as indicated by the arrows) and are also used in gluconeogenesis.","Like glycolysis, there is an additional regulation here by the bifunctional enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase (figure 4.1). This bifunctional enzyme functions as a kinase in the fed state (PFK2) and generates fructose 2,6-bisphosphate that allosterically activates PFK1. In the fasted state the enzyme is phosphorylated by glucagon-activated protein kinase A, and this actives the phosphatase activity of the enzyme. The enzyme dephosphorylates fructose 2,6-bisphosphate and therefore reduces the allosteric activation of PFK1 facilitating the reverse reaction by fructose 1,6-bisphosphatase (figure 5.2).","{'12c5c357-49fb-4f02-8d67-cf4e9a649d4b': 'As PEP continues through the reverse of glycolysis, fructose 1,6-bisphosphate is generated. To bypass the irreversible step catalyzed by phosphofructokinase 1 (PFK1) in glycolysis, the enzyme fructose 1,6-bisphosphatase (FBP1) is present and dephosphorylates fructose 1,6-bisphosphate to produce fructose 6-phosphate. This enzyme, FBP1, is inhibited by AMP and fructose 2,6-bisphosphate (figure 5.2).', 'a9b7cea1-4ae3-4760-b736-cbe9e0e7eaa4': 'Like glycolysis, there is an additional regulation here by the bifunctional enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase (figure 4.1). This bifunctional enzyme functions as a kinase in the fed state (PFK2) and generates fructose 2,6-bisphosphate that allosterically activates PFK1. In the fasted state the enzyme is phosphorylated by glucagon-activated protein kinase A, and this actives the phosphatase activity of the enzyme. The enzyme dephosphorylates fructose 2,6-bisphosphate and therefore reduces the allosteric activation of PFK1 facilitating the reverse reaction by fructose 1,6-bisphosphatase (figure 5.2).', 'afd375b8-13ae-4f33-9191-ec36c46ba669': 'Glycolysis in the liver has three primary regulated and irreversible steps (figure 4.1).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.6,cell_bio/images/Figure 5.6.jpg,Figure 5.6: Hepatic glycogenolysis by epinephrine.,"In the liver, glucagon will initiate glycogenolysis through a GPCR-mediated signaling cascade. This leads to the activation of adenylyl cyclase and an increase in cAMP. cAMP activates protein kinase A, which phosphorylates and activates glycogen phosphorylase. Glycogen phosphorylase will initiate glycogen degradation. Also under these conditions, using the same mechanism, glycogen synthase will be phosphorylated and inactivated, ensuring glycogen synthesis is not occurring at the same time (figure 5.6).","{'fa5d48ba-43a0-4051-aa22-ab6715431fd8': 'In the liver, glucagon will initiate glycogenolysis through a GPCR-mediated signaling cascade. This leads to the activation of adenylyl cyclase and an increase in cAMP. cAMP activates protein kinase A, which phosphorylates and activates glycogen phosphorylase. Glycogen phosphorylase will initiate glycogen degradation. Also under these conditions, using the same mechanism, glycogen synthase will be phosphorylated and inactivated, ensuring glycogen synthesis is not occurring at the same time (figure 5.6).', '0136b268-ce9f-421f-a8e0-ac901b689c59': 'Epinephrine can also enhance hepatic glycogenolysis by binding an α-agonist receptor. This initiates the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-triphosphate (IP3) and diacylglyerol (DAG) by phospholipase C. IP3 stimulates Ca2+ release from endoplasmic reticulum and results in both:', '580d830e-0119-4afc-9404-ff5e83fc86f0': 'In all cases, the glucose 6-phosphate released from glycogen stores is dephosphorylated by glucose 6-phosphatase and released from the liver.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', 'c84fb514-70b7-4c18-8cbe-8a0feba2d288': 'Lipolysis is the release of fatty acids from adipose tissue where they are stored as triacylglycerols (TAGs). This process is mediated by increasing levels of glucagon and epinephrine, which bind G-protein coupled receptors on the adipose tissue and activate lipolysis This cell-signaling cascade phosphorylates and activates hormone-sensitive lipase, the regulatory enzyme for lipolysis. Once phosphorylated (through hormone-mediated increase in cAMP) this enzyme will hydrolyze TAGs to three\xa0long-chain fatty acids (LCFAs) and glycerol. The LCFAs are released into the bloodstream and will circulate bound to albumin (fatty acids are hydrophobic and require a protein carrier). LCFAs will be taken up and oxidized by peripheral tissues and the liver under fasted conditions. The glycerol will also be released and used as a substrate for hepatic gluconeogenesis (section 5.1) (figure 5.6).'}"
Figure 5.7,cell_bio/images/Figure 5.7.jpg,Figure 5.7: Skeletal muscle glycogenolysis.,"Skeletal muscle glycogen is not impacted by glucagon but responds to AMP, Ca2+, and epinephrine (figure 5.7).","{'3c6aa6e4-a20f-4622-968a-8135e39ad619': 'Skeletal muscle glycogen is not impacted by glucagon but responds to AMP, Ca2+, and epinephrine (figure 5.7).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.1,cell_bio/images/Figure 5.1.jpg,Figure 5.1: Glucose production by glycogenolysis and gluconeogenesis.,"Gluconeogenesis and glycogenolysis are the two pathways essential for glucose homeostasis. Figure 5.1 illustrates the time frame and overlap of glycogenolysis and gluconeogenesis. These pathways are activated nearly simultaneously when the insulin to glucagon ratio becomes sufficiently reduced. Over time, the reliance on the pathways changes.","{'c47897ec-9681-4c6c-95b1-08fe4cfe0234': 'Glycogenolysis (see section 4.5)', 'be5d552c-0325-4f4a-bb11-c49abb636892': 'Gluconeogenesis and glycogenolysis are the two pathways essential for glucose homeostasis. Figure 5.1 illustrates the time frame and overlap of glycogenolysis and gluconeogenesis. These pathways are activated nearly simultaneously when the insulin to glucagon ratio becomes sufficiently reduced. Over time, the reliance on the pathways changes.', 'e3b226cb-1f77-4afc-815b-e7daab1dbe0d': 'Gluconeogenesis (GNG) is an anabolic pathway that produces glucose from lactate, glycerol, or glucogenic amino acids. This pathway is activated primarily in the liver during fasting and is coordinated with the catabolic pathways of β-oxidation and protein catabolism. The pathway follows the reverse of glycolysis with the exception of four unique enzymes, which overcome the irreversible steps of glycolysis (figure 5.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.2,cell_bio/images/Figure 5.2.jpg,Figure 5.2: Comparison of glycolysis and gluconeogenesis.,"Gluconeogenesis (GNG) is an anabolic pathway that produces glucose from lactate, glycerol, or glucogenic amino acids. This pathway is activated primarily in the liver during fasting and is coordinated with the catabolic pathways of β-oxidation and protein catabolism. The pathway follows the reverse of glycolysis with the exception of four unique enzymes, which overcome the irreversible steps of glycolysis (figure 5.2).","{'c47897ec-9681-4c6c-95b1-08fe4cfe0234': 'Glycogenolysis (see section 4.5)', 'be5d552c-0325-4f4a-bb11-c49abb636892': 'Gluconeogenesis and glycogenolysis are the two pathways essential for glucose homeostasis. Figure 5.1 illustrates the time frame and overlap of glycogenolysis and gluconeogenesis. These pathways are activated nearly simultaneously when the insulin to glucagon ratio becomes sufficiently reduced. Over time, the reliance on the pathways changes.', 'e3b226cb-1f77-4afc-815b-e7daab1dbe0d': 'Gluconeogenesis (GNG) is an anabolic pathway that produces glucose from lactate, glycerol, or glucogenic amino acids. This pathway is activated primarily in the liver during fasting and is coordinated with the catabolic pathways of β-oxidation and protein catabolism. The pathway follows the reverse of glycolysis with the exception of four unique enzymes, which overcome the irreversible steps of glycolysis (figure 5.2).', '977b4b53-5358-41f0-8d9f-4ff563e872f7': 'Gluconeogenesis is essentially the reverse of glycolysis with four\xa0key regulatory steps that allow the bypass of the three\xa0irreversible steps of glycolysis (figure 5.2). This initial step of GNG starts in the mitochondria using pyruvate carboxylase (figure 5.5). This enzyme converts pyruvate in the mitochondria to oxaloacetate and requires biotin as a cofactor. This enzyme is allosterically activated by acetyl-CoA. The OAA produced is reduced to malate, which is shuttled out of the mitochondria using the malate-aspartate shuttle. Once in the cytosol, the malate is oxidized back to OAA and decarboxylated by the enzyme phosphoenol carboxykinase (PEPCK) to generate phosphoenol pyruvate (figure 5.3). The combination of these two enzymes, pyruvate carboxylase and PEPCK, allows the cell to bypass the irreversible step catalyzed by pyruvate kinase.', '468dd3a5-1956-4116-8626-1ce68cda9a38': 'Once phosphoenol pyruvate (PEP) is synthesized, it will continue through the reverse process using the glycolytic enzymes until it reaches its next irreversible conversion.', '12c5c357-49fb-4f02-8d67-cf4e9a649d4b': 'As PEP continues through the reverse of glycolysis, fructose 1,6-bisphosphate is generated. To bypass the irreversible step catalyzed by phosphofructokinase 1 (PFK1) in glycolysis, the enzyme fructose 1,6-bisphosphatase (FBP1) is present and dephosphorylates fructose 1,6-bisphosphate to produce fructose 6-phosphate. This enzyme, FBP1, is inhibited by AMP and fructose 2,6-bisphosphate (figure 5.2).', 'a9b7cea1-4ae3-4760-b736-cbe9e0e7eaa4': 'Like glycolysis, there is an additional regulation here by the bifunctional enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase (figure 4.1). This bifunctional enzyme functions as a kinase in the fed state (PFK2) and generates fructose 2,6-bisphosphate that allosterically activates PFK1. In the fasted state the enzyme is phosphorylated by glucagon-activated protein kinase A, and this actives the phosphatase activity of the enzyme. The enzyme dephosphorylates fructose 2,6-bisphosphate and therefore reduces the allosteric activation of PFK1 facilitating the reverse reaction by fructose 1,6-bisphosphatase (figure 5.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.3,cell_bio/images/Figure 5.3.jpg,Figure 5.3: Locations of amino acid and lactate entering gluconeogenesis as substrates for the pathway.,"Lactate is primarily produced through the Cori cycle or from anaerobic glucose oxidation. (Note: The Cori cycle, or lactic acid cycle, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscle or RBC travels to the liver and is converted to glucose. The glucose returns to the peripheral tissues and is metabolized back to lactate.) Once in the liver, lactate can be oxidized back to pyruvate through the reverse reaction catalyzed by lactate dehydrogenase (figure 5.3).","{'c827d3f2-88d2-4b93-9996-ea3bb4eb386e': 'Lactate is primarily produced through the Cori cycle or from anaerobic glucose oxidation. (Note: The Cori cycle, or lactic acid cycle, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscle or RBC travels to the liver and is converted to glucose. The glucose returns to the peripheral tissues and is metabolized back to lactate.)\xa0Once in the liver, lactate can be oxidized back to pyruvate through the reverse reaction catalyzed by lactate dehydrogenase (figure 5.3).', 'a1bd4d19-e758-479c-b85d-67408c03c539': 'Serum lactate levels may also be measured in conjunction with a complete metabolic panel. Serum lactate should be negligible under normal conditions, however, elevated lactate could be suggestive of excessive anaerobic metabolism, such as is the case in intense exercise or deficiency in oxygen transport caused by ischemic injury. This could also be caused by inappropriate diversion of substrate such as is the case in some enzymatic deficiencies (pyruvate dehydrogenase deficiency) or changes in NADH levels (figure 2.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', 'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 5.4,cell_bio/images/Figure 5.4.jpg,"Figure 5.4: Glycerol as a substrate for gluconeogenesis; after phosphorylation to glycerol 3-phosphate it can be converted to DHAP, which can enter directly into glycolysis.","When lipolysis is stimulated by epinephrine or glucagon, activation of hormone-sensitive lipase in the adipose allows for the hydrolysis of triacylglycerol into three free fatty acid chains and glycerol. The glycerol released into circulation will be taken up by the liver. Once in the liver it can be converted into dihydroxyacetone phosphate (DHAP), a glycolytic intermediate. This is an additional way in which carbons can be obtained for glucose synthesis (figure 5.4).","{'cc7d6716-b10f-4fb4-b3a9-06aa2d5b05dd': 'When lipolysis is stimulated by epinephrine or glucagon, activation of hormone-sensitive lipase in the adipose allows for the hydrolysis of triacylglycerol into three free fatty acid chains and glycerol. The glycerol released into circulation will be taken up by the liver. Once in the liver it can be converted into dihydroxyacetone phosphate (DHAP), a glycolytic intermediate. This is an additional way in which carbons can be obtained for glucose synthesis (figure 5.4).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.5,cell_bio/images/Figure 5.5.jpg,,Figure 5.5: Reaction catalyzed by pyruvate carboxylase; this allows the bypass of the irreversible step catalyzed by pyruvate kinase.,"{'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.7,cell_bio/images/Figure 5.7.jpg,Figure 5.7: Skeletal muscle glycogenolysis.,"Skeletal muscle glycogen is not impacted by glucagon but responds to AMP, Ca2+, and epinephrine (figure 5.7).","{'3c6aa6e4-a20f-4622-968a-8135e39ad619': 'Skeletal muscle glycogen is not impacted by glucagon but responds to AMP, Ca2+, and epinephrine (figure 5.7).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 5.6,cell_bio/images/Figure 5.6.jpg,Figure 5.6: Hepatic glycogenolysis by epinephrine.,"In the liver, glucagon will initiate glycogenolysis through a GPCR-mediated signaling cascade. This leads to the activation of adenylyl cyclase and an increase in cAMP. cAMP activates protein kinase A, which phosphorylates and activates glycogen phosphorylase. Glycogen phosphorylase will initiate glycogen degradation. Also under these conditions, using the same mechanism, glycogen synthase will be phosphorylated and inactivated, ensuring glycogen synthesis is not occurring at the same time (figure 5.6).","{'fa5d48ba-43a0-4051-aa22-ab6715431fd8': 'In the liver, glucagon will initiate glycogenolysis through a GPCR-mediated signaling cascade. This leads to the activation of adenylyl cyclase and an increase in cAMP. cAMP activates protein kinase A, which phosphorylates and activates glycogen phosphorylase. Glycogen phosphorylase will initiate glycogen degradation. Also under these conditions, using the same mechanism, glycogen synthase will be phosphorylated and inactivated, ensuring glycogen synthesis is not occurring at the same time (figure 5.6).', '0136b268-ce9f-421f-a8e0-ac901b689c59': 'Epinephrine can also enhance hepatic glycogenolysis by binding an α-agonist receptor. This initiates the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-triphosphate (IP3) and diacylglyerol (DAG) by phospholipase C. IP3 stimulates Ca2+ release from endoplasmic reticulum and results in both:', '580d830e-0119-4afc-9404-ff5e83fc86f0': 'In all cases, the glucose 6-phosphate released from glycogen stores is dephosphorylated by glucose 6-phosphatase and released from the liver.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', 'c84fb514-70b7-4c18-8cbe-8a0feba2d288': 'Lipolysis is the release of fatty acids from adipose tissue where they are stored as triacylglycerols (TAGs). This process is mediated by increasing levels of glucagon and epinephrine, which bind G-protein coupled receptors on the adipose tissue and activate lipolysis This cell-signaling cascade phosphorylates and activates hormone-sensitive lipase, the regulatory enzyme for lipolysis. Once phosphorylated (through hormone-mediated increase in cAMP) this enzyme will hydrolyze TAGs to three\xa0long-chain fatty acids (LCFAs) and glycerol. The LCFAs are released into the bloodstream and will circulate bound to albumin (fatty acids are hydrophobic and require a protein carrier). LCFAs will be taken up and oxidized by peripheral tissues and the liver under fasted conditions. The glycerol will also be released and used as a substrate for hepatic gluconeogenesis (section 5.1) (figure 5.6).'}"
Figure 5.6,cell_bio/images/Figure 5.6.jpg,Figure 5.6: Hepatic glycogenolysis by epinephrine.,"In the liver, glucagon will initiate glycogenolysis through a GPCR-mediated signaling cascade. This leads to the activation of adenylyl cyclase and an increase in cAMP. cAMP activates protein kinase A, which phosphorylates and activates glycogen phosphorylase. Glycogen phosphorylase will initiate glycogen degradation. Also under these conditions, using the same mechanism, glycogen synthase will be phosphorylated and inactivated, ensuring glycogen synthesis is not occurring at the same time (figure 5.6).","{'fa5d48ba-43a0-4051-aa22-ab6715431fd8': 'In the liver, glucagon will initiate glycogenolysis through a GPCR-mediated signaling cascade. This leads to the activation of adenylyl cyclase and an increase in cAMP. cAMP activates protein kinase A, which phosphorylates and activates glycogen phosphorylase. Glycogen phosphorylase will initiate glycogen degradation. Also under these conditions, using the same mechanism, glycogen synthase will be phosphorylated and inactivated, ensuring glycogen synthesis is not occurring at the same time (figure 5.6).', '0136b268-ce9f-421f-a8e0-ac901b689c59': 'Epinephrine can also enhance hepatic glycogenolysis by binding an α-agonist receptor. This initiates the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-triphosphate (IP3) and diacylglyerol (DAG) by phospholipase C. IP3 stimulates Ca2+ release from endoplasmic reticulum and results in both:', '580d830e-0119-4afc-9404-ff5e83fc86f0': 'In all cases, the glucose 6-phosphate released from glycogen stores is dephosphorylated by glucose 6-phosphatase and released from the liver.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', 'c84fb514-70b7-4c18-8cbe-8a0feba2d288': 'Lipolysis is the release of fatty acids from adipose tissue where they are stored as triacylglycerols (TAGs). This process is mediated by increasing levels of glucagon and epinephrine, which bind G-protein coupled receptors on the adipose tissue and activate lipolysis This cell-signaling cascade phosphorylates and activates hormone-sensitive lipase, the regulatory enzyme for lipolysis. Once phosphorylated (through hormone-mediated increase in cAMP) this enzyme will hydrolyze TAGs to three\xa0long-chain fatty acids (LCFAs) and glycerol. The LCFAs are released into the bloodstream and will circulate bound to albumin (fatty acids are hydrophobic and require a protein carrier). LCFAs will be taken up and oxidized by peripheral tissues and the liver under fasted conditions. The glycerol will also be released and used as a substrate for hepatic gluconeogenesis (section 5.1) (figure 5.6).'}"
Figure 5.9,cell_bio/images/Figure 5.9.jpg,Figure 5.9: Overview of LCFA transport into the mitochondria and β-oxidation.,"Fatty acid oxidation is a high energy yielding process. It can support the cellular energy needs during fasting and under conditions when excess energy is needed (exercise). After uptake from circulation, the LCFAs must be transferred into the mitochondria where β-oxidation occurs. Initially, the LCFAs are activated to acyl-CoA derivatives in the cytosol by acyl-CoA synthetase. The fatty acyl-CoA can then be transferred across the mitochondrial membranes using a series of transport proteins: carnitine palmitoyltransferase 1 and 2 (CPT1 and CPT2) (figure 5.9).","{'7090d0cb-1e2e-4de6-8726-0e196ce4b830': 'Fatty acid oxidation is a high energy yielding process. It can support the cellular energy needs during fasting and under conditions when excess energy is needed (exercise). After uptake from circulation, the LCFAs must be transferred into the mitochondria where β-oxidation occurs. Initially, the LCFAs are activated to acyl-CoA derivatives in the cytosol by acyl-CoA synthetase. The fatty acyl-CoA can then be transferred across the mitochondrial membranes using a series of transport proteins: carnitine palmitoyltransferase 1 and 2 (CPT1 and CPT2) (figure 5.9).', 'c406f662-2904-4039-8c73-323a6642e996': 'CPT1 sits on the outer mitochondrial membrane and transfers the fatty acyl-CoA to carnitine. Fatty acyl carnitine is transferred into the mitochondrial matrix through CPT2, and the carnitine is released and recycled. Only long-chain fatty acyl-CoAs require carnitine as a carrier; short- and medium-chain fatty acids can move into the mitochondria without the assistance of these transporters. Once in the matrix, the fatty acyl-CoA is now ready to undergo β-oxidation (figure 5.9).', '4d7d6248-5b8e-4594-89dd-8596d6e31a76': 'β-oxidation is an iterative process that involves a series of enzymes that preferentially oxidize different length fatty acids (long, medium, and short). The full β-oxidation spiral consists of four steps that result in the generation of acetyl-CoA, NADH, and FADH2 for each cycle (figure 5.9). The NADH and FADH2 generated will be oxidized in the ETC to produce ATP. The acetyl-CoA can be oxidized in the TCA cycle, but more likely it will be used in ketogenesis. Oxidation of odd chain fatty acids will result in the generation of propionyl-CoA as the final carbon unit, which can also be oxidized in the TCA cycle. The acetyl-CoA from β-oxidation also plays a key role in the allosteric activation of pyruvate carboxylase, which is necessary for gluconeogenesis to occur (section 5.1).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 5.10,cell_bio/images/Figure 5.10.jpg,Figure 5.10: Regulation of β-oxidation.,"β-oxidation is regulated primarily at the level of transport of LCFAs across the mitochondrial membrane. Malonyl-CoA will inhibit CPT1 therefore ensuring that β-oxidation is not occurring at the same time as fatty acid synthesis (figure 5.10; section 4.4). Additionally, the rate of ATP production (ATP/ADP ratio) will also regulate the rate of NADH and FADH2 produced through β-oxidation (figure 5.10).","{'d2e1ace2-a3cc-4495-b382-beb7d66696ab': 'β-oxidation is regulated primarily at the level of transport of LCFAs across the mitochondrial membrane. Malonyl-CoA will inhibit CPT1 therefore ensuring that β-oxidation is not occurring at the same time as fatty acid synthesis (figure 5.10; section 4.4). Additionally, the rate of ATP production (ATP/ADP ratio) will also regulate the rate of NADH and FADH2 produced through β-oxidation (figure 5.10).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 5.11,cell_bio/images/Figure 5.11.jpg,Figure 5.11: Overview of ketone body formation.,"The primary substrates for GNG are derived from glucogenic amino acids released through cortisol-mediated protein catabolism. In the fasted state, cortisol is elevated, and it supports fasted state pathways through the activation of protein catabolism — in the skeletal muscle — and by increasing the transcription of enzymes needed for gluconeogenesis (specifically phosphoenol carboxykinase (PEPCK)). As amino acids are released from the skeletal muscle, primarily as glutamine and alanine, they are taken up by the liver. In order to be used for glucose synthesis, they undergo transamination to generate a useful intermediate of the TCA cycle, predominantly α-ketoglutarate and pyruvate (see figures 5.3 and 5.10) . In the case of alanine, this can be transaminated to generate pyruvate. Glutamine will first be deaminated by glutaminase, and the remaining glutamate will be transaminated to form α-ketoglutarate (see figure 5.11). Both pyruvate and α-ketoglutarate will increase substrates in the TCA cycle, ultimately increasing the pool of available malate to be shuttled out of the mitochondria. It is through this process of protein catabolism and transamination that glucogenic amino acids contribute to the synthesis of oxaloacetate (OAA) needed for gluconeogenesis.","{'791a7b80-2845-490c-b751-394d6b7310e7': 'The primary substrates for GNG are derived from glucogenic amino acids released through cortisol-mediated protein catabolism. In the fasted state, cortisol is elevated, and it supports fasted state pathways through the activation of protein catabolism —\xa0in the skeletal muscle —\xa0and by increasing the transcription of enzymes needed for gluconeogenesis (specifically phosphoenol carboxykinase (PEPCK)). As amino acids are released from the skeletal muscle, primarily as glutamine and alanine, they are taken up by the liver. In order to be used for glucose synthesis, they undergo transamination to generate a useful intermediate of the TCA cycle, predominantly α-ketoglutarate and pyruvate (see figures 5.3 and 5.10) . In the case of alanine, this can be transaminated to generate pyruvate. Glutamine will first be deaminated by glutaminase, and the remaining glutamate will be transaminated to form α-ketoglutarate (see figure 5.11). Both pyruvate and α-ketoglutarate will increase substrates in the TCA cycle, ultimately increasing the pool of available malate to be shuttled out of the mitochondria. It is through this process of protein catabolism and transamination that glucogenic amino acids contribute to the synthesis of oxaloacetate (OAA) needed for gluconeogenesis.', '7592682d-cc74-44e6-8c22-01de8a817bb1': 'As mentioned above, the acetyl-CoA produced by β-oxidation is primarily used for ketogenesis — the synthesis of ketone bodies. Substrates for ketogenesis can also come from the oxidation of ketogenic amino acids. In the fasted state, the process of β-oxidation generates a significant amount of acetyl-CoA, and although some of this substrate can be oxidized in the TCA cycle, we need to consider the other metabolic processes occurring. First, the significant amount of NADH generated through β-oxidation reduces flux through the TCA cycle by decreasing the activity of both α-ketoglutarate dehydrogenase and isocitrate dehydrogenase. Second, the process of gluconeogenesis is occurring, and intermediates of the TCA cycle, specifically malate, are actively being moved out of the mitochondria. The combination of these two processes reduces the TCA cycle activity allowing for an accumulation of acetyl-CoA. As acetyl-CoA levels elevate in the mitochondria, this will drive the thiolase reaction to generate acetoacetyl-CoA from two acetyl-CoA molecules (figure 5.11).', 'e8b2c041-78e0-45e7-ba6c-31161566065c': 'This compound is the substrate for HMG-CoA synthase, which generates 3-hydroxy-3-methyl glutaryl-CoA (HMG-CoA). HMG-CoA is then accepted by HMG-CoA lyase where an acetyl-CoA group is removed to generate acetoacetate. Acetoacetate can either undergo spontaneous decarboxylation to acetone, which can be exhaled, or it can be reduced to β-hydroxybutyrate using NADH. Acetoacetate and β-hydroxybutyrate are the two primary ketone bodies in circulation, and the ratio of the two is dependent on levels of NADH (figure 5.11). These two ketone bodies can be used as fuel in most tissues with the exception of the liver, which lacks thiophorase, the enzyme needed to metabolize these substrates. Ketone oxidation is not a primary fuel source, as fatty acid oxidation is preferred, but it can supply energy to some peripheral tissues. The brain can also oxidize ketones but only under extreme situations, such as starvation states.', 'eec41915-2c09-4a80-94e9-742520e4e4d8': 'Table 5.2: Summary of pathway regulation.', '76872677-0281-4e4f-b803-3400ad732ead': '5.2 References and resources', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 5.8,cell_bio/images/Figure 5.8.jpg,,Figure 5.8: Process of lipolysis.,"{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 5.9,cell_bio/images/Figure 5.9.jpg,Figure 5.9: Overview of LCFA transport into the mitochondria and β-oxidation.,"Fatty acid oxidation is a high energy yielding process. It can support the cellular energy needs during fasting and under conditions when excess energy is needed (exercise). After uptake from circulation, the LCFAs must be transferred into the mitochondria where β-oxidation occurs. Initially, the LCFAs are activated to acyl-CoA derivatives in the cytosol by acyl-CoA synthetase. The fatty acyl-CoA can then be transferred across the mitochondrial membranes using a series of transport proteins: carnitine palmitoyltransferase 1 and 2 (CPT1 and CPT2) (figure 5.9).","{'7090d0cb-1e2e-4de6-8726-0e196ce4b830': 'Fatty acid oxidation is a high energy yielding process. It can support the cellular energy needs during fasting and under conditions when excess energy is needed (exercise). After uptake from circulation, the LCFAs must be transferred into the mitochondria where β-oxidation occurs. Initially, the LCFAs are activated to acyl-CoA derivatives in the cytosol by acyl-CoA synthetase. The fatty acyl-CoA can then be transferred across the mitochondrial membranes using a series of transport proteins: carnitine palmitoyltransferase 1 and 2 (CPT1 and CPT2) (figure 5.9).', 'c406f662-2904-4039-8c73-323a6642e996': 'CPT1 sits on the outer mitochondrial membrane and transfers the fatty acyl-CoA to carnitine. Fatty acyl carnitine is transferred into the mitochondrial matrix through CPT2, and the carnitine is released and recycled. Only long-chain fatty acyl-CoAs require carnitine as a carrier; short- and medium-chain fatty acids can move into the mitochondria without the assistance of these transporters. Once in the matrix, the fatty acyl-CoA is now ready to undergo β-oxidation (figure 5.9).', '4d7d6248-5b8e-4594-89dd-8596d6e31a76': 'β-oxidation is an iterative process that involves a series of enzymes that preferentially oxidize different length fatty acids (long, medium, and short). The full β-oxidation spiral consists of four steps that result in the generation of acetyl-CoA, NADH, and FADH2 for each cycle (figure 5.9). The NADH and FADH2 generated will be oxidized in the ETC to produce ATP. The acetyl-CoA can be oxidized in the TCA cycle, but more likely it will be used in ketogenesis. Oxidation of odd chain fatty acids will result in the generation of propionyl-CoA as the final carbon unit, which can also be oxidized in the TCA cycle. The acetyl-CoA from β-oxidation also plays a key role in the allosteric activation of pyruvate carboxylase, which is necessary for gluconeogenesis to occur (section 5.1).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 5.10,cell_bio/images/Figure 5.10.jpg,Figure 5.10: Regulation of β-oxidation.,"β-oxidation is regulated primarily at the level of transport of LCFAs across the mitochondrial membrane. Malonyl-CoA will inhibit CPT1 therefore ensuring that β-oxidation is not occurring at the same time as fatty acid synthesis (figure 5.10; section 4.4). Additionally, the rate of ATP production (ATP/ADP ratio) will also regulate the rate of NADH and FADH2 produced through β-oxidation (figure 5.10).","{'d2e1ace2-a3cc-4495-b382-beb7d66696ab': 'β-oxidation is regulated primarily at the level of transport of LCFAs across the mitochondrial membrane. Malonyl-CoA will inhibit CPT1 therefore ensuring that β-oxidation is not occurring at the same time as fatty acid synthesis (figure 5.10; section 4.4). Additionally, the rate of ATP production (ATP/ADP ratio) will also regulate the rate of NADH and FADH2 produced through β-oxidation (figure 5.10).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 5.11,cell_bio/images/Figure 5.11.jpg,Figure 5.11: Overview of ketone body formation.,"The primary substrates for GNG are derived from glucogenic amino acids released through cortisol-mediated protein catabolism. In the fasted state, cortisol is elevated, and it supports fasted state pathways through the activation of protein catabolism — in the skeletal muscle — and by increasing the transcription of enzymes needed for gluconeogenesis (specifically phosphoenol carboxykinase (PEPCK)). As amino acids are released from the skeletal muscle, primarily as glutamine and alanine, they are taken up by the liver. In order to be used for glucose synthesis, they undergo transamination to generate a useful intermediate of the TCA cycle, predominantly α-ketoglutarate and pyruvate (see figures 5.3 and 5.10) . In the case of alanine, this can be transaminated to generate pyruvate. Glutamine will first be deaminated by glutaminase, and the remaining glutamate will be transaminated to form α-ketoglutarate (see figure 5.11). Both pyruvate and α-ketoglutarate will increase substrates in the TCA cycle, ultimately increasing the pool of available malate to be shuttled out of the mitochondria. It is through this process of protein catabolism and transamination that glucogenic amino acids contribute to the synthesis of oxaloacetate (OAA) needed for gluconeogenesis.","{'791a7b80-2845-490c-b751-394d6b7310e7': 'The primary substrates for GNG are derived from glucogenic amino acids released through cortisol-mediated protein catabolism. In the fasted state, cortisol is elevated, and it supports fasted state pathways through the activation of protein catabolism —\xa0in the skeletal muscle —\xa0and by increasing the transcription of enzymes needed for gluconeogenesis (specifically phosphoenol carboxykinase (PEPCK)). As amino acids are released from the skeletal muscle, primarily as glutamine and alanine, they are taken up by the liver. In order to be used for glucose synthesis, they undergo transamination to generate a useful intermediate of the TCA cycle, predominantly α-ketoglutarate and pyruvate (see figures 5.3 and 5.10) . In the case of alanine, this can be transaminated to generate pyruvate. Glutamine will first be deaminated by glutaminase, and the remaining glutamate will be transaminated to form α-ketoglutarate (see figure 5.11). Both pyruvate and α-ketoglutarate will increase substrates in the TCA cycle, ultimately increasing the pool of available malate to be shuttled out of the mitochondria. It is through this process of protein catabolism and transamination that glucogenic amino acids contribute to the synthesis of oxaloacetate (OAA) needed for gluconeogenesis.', '7592682d-cc74-44e6-8c22-01de8a817bb1': 'As mentioned above, the acetyl-CoA produced by β-oxidation is primarily used for ketogenesis — the synthesis of ketone bodies. Substrates for ketogenesis can also come from the oxidation of ketogenic amino acids. In the fasted state, the process of β-oxidation generates a significant amount of acetyl-CoA, and although some of this substrate can be oxidized in the TCA cycle, we need to consider the other metabolic processes occurring. First, the significant amount of NADH generated through β-oxidation reduces flux through the TCA cycle by decreasing the activity of both α-ketoglutarate dehydrogenase and isocitrate dehydrogenase. Second, the process of gluconeogenesis is occurring, and intermediates of the TCA cycle, specifically malate, are actively being moved out of the mitochondria. The combination of these two processes reduces the TCA cycle activity allowing for an accumulation of acetyl-CoA. As acetyl-CoA levels elevate in the mitochondria, this will drive the thiolase reaction to generate acetoacetyl-CoA from two acetyl-CoA molecules (figure 5.11).', 'e8b2c041-78e0-45e7-ba6c-31161566065c': 'This compound is the substrate for HMG-CoA synthase, which generates 3-hydroxy-3-methyl glutaryl-CoA (HMG-CoA). HMG-CoA is then accepted by HMG-CoA lyase where an acetyl-CoA group is removed to generate acetoacetate. Acetoacetate can either undergo spontaneous decarboxylation to acetone, which can be exhaled, or it can be reduced to β-hydroxybutyrate using NADH. Acetoacetate and β-hydroxybutyrate are the two primary ketone bodies in circulation, and the ratio of the two is dependent on levels of NADH (figure 5.11). These two ketone bodies can be used as fuel in most tissues with the exception of the liver, which lacks thiophorase, the enzyme needed to metabolize these substrates. Ketone oxidation is not a primary fuel source, as fatty acid oxidation is preferred, but it can supply energy to some peripheral tissues. The brain can also oxidize ketones but only under extreme situations, such as starvation states.', 'eec41915-2c09-4a80-94e9-742520e4e4d8': 'Table 5.2: Summary of pathway regulation.', '76872677-0281-4e4f-b803-3400ad732ead': '5.2 References and resources', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 5.14,cell_bio/images/Figure 5.14.jpg,Figure 5.14: Movement of ammonia from peripheral tissues to the liver.,"In addition to transaminases, there are three other enzymes that play essential roles in nitrogen transport. Glutamate dehydrogenase (GDH) is present in most tissues and is one of the few enzymes able to fix or free ammonia. In figure 5.14, in the skeletal muscle, glutamate dehydrogenase is illustrated fixing ammonia to α-ketoglutarate to generate glutamate, while in the liver it is shown freeing ammonia in the reverse reaction. The direction of the reaction will be influenced by several factors including cellular needs, the levels of NAD+ or NADP+, and levels of ammonia (figure 5.14).","{'719c0809-1e48-4c89-aba5-84881dc6f07e': 'In addition to transaminases, there are three other enzymes that play essential roles in nitrogen transport. Glutamate dehydrogenase (GDH) is present in most tissues and is one of the few enzymes able to fix or free ammonia. In figure 5.14, in the skeletal muscle, glutamate dehydrogenase is illustrated fixing ammonia to α-ketoglutarate to generate glutamate, while in the liver it is shown freeing ammonia in the reverse reaction. The direction of the reaction will be influenced by several factors including cellular needs, the levels of NAD+ or NADP+, and levels of ammonia (figure 5.14).', '7c1ca1ac-8a56-4c9f-a40f-459b1c72a858': 'In peripheral tissues, glutamate generated from transamination or from the GDH reaction can be used to fix an additional ammonia to generate glutamine. This reaction, catalyzed by glutamine synthetase, facilitates the synthesis and subsequent movement of excess nitrogen from peripheral tissues to the liver (figure 5.14).', '4e735630-8767-4095-a6e4-f4e8ba10fa4f': 'In skeletal muscle, the alanine-glucose cycle is commonly used for the transport of nitrogen from the skeletal muscle to the liver. In this process, ammonia from amino acid degradation is transaminated to form glutamate. Alanine aminotransferase (AST) will transaminate glutamate with pyruvate to generate alanine (and α-ketoglutarate). The alanine is released and transported to the liver where it will undergo another transamination to generate pyruvate, which is used as a substrate for glucose production (gluconeogenesis). The glucose is released from the liver and oxidized by the skeletal muscle.', '31da73ee-240e-49ce-9d81-6f2223ca0127': 'The other key enzyme in nitrogen metabolism is glutaminase. Glutaminase, is active in the liver and responsible for deaminating glutamine as it is shuttled into the liver. The free ammonia can enter into the urea cycle, and the remaining glutamate can be transaminated to generate α-ketoglutarate. This is in contrast to glutamine synthetase, which is primarily used by peripheral tissues as a means of generating glutamine to remove ammonia from the tissues to the liver (figure 5.14). Nitrogen metabolism, unlike glucose metabolism, is fairly consistent in the fed and fasted states. Excess dietary amino acids, which are not stored, will also require deamination, and the carbons can be stored as either glycogen or fat.', 'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 5.14,cell_bio/images/Figure 5.14.jpg,Figure 5.14: Movement of ammonia from peripheral tissues to the liver.,"In addition to transaminases, there are three other enzymes that play essential roles in nitrogen transport. Glutamate dehydrogenase (GDH) is present in most tissues and is one of the few enzymes able to fix or free ammonia. In figure 5.14, in the skeletal muscle, glutamate dehydrogenase is illustrated fixing ammonia to α-ketoglutarate to generate glutamate, while in the liver it is shown freeing ammonia in the reverse reaction. The direction of the reaction will be influenced by several factors including cellular needs, the levels of NAD+ or NADP+, and levels of ammonia (figure 5.14).","{'719c0809-1e48-4c89-aba5-84881dc6f07e': 'In addition to transaminases, there are three other enzymes that play essential roles in nitrogen transport. Glutamate dehydrogenase (GDH) is present in most tissues and is one of the few enzymes able to fix or free ammonia. In figure 5.14, in the skeletal muscle, glutamate dehydrogenase is illustrated fixing ammonia to α-ketoglutarate to generate glutamate, while in the liver it is shown freeing ammonia in the reverse reaction. The direction of the reaction will be influenced by several factors including cellular needs, the levels of NAD+ or NADP+, and levels of ammonia (figure 5.14).', '7c1ca1ac-8a56-4c9f-a40f-459b1c72a858': 'In peripheral tissues, glutamate generated from transamination or from the GDH reaction can be used to fix an additional ammonia to generate glutamine. This reaction, catalyzed by glutamine synthetase, facilitates the synthesis and subsequent movement of excess nitrogen from peripheral tissues to the liver (figure 5.14).', '4e735630-8767-4095-a6e4-f4e8ba10fa4f': 'In skeletal muscle, the alanine-glucose cycle is commonly used for the transport of nitrogen from the skeletal muscle to the liver. In this process, ammonia from amino acid degradation is transaminated to form glutamate. Alanine aminotransferase (AST) will transaminate glutamate with pyruvate to generate alanine (and α-ketoglutarate). The alanine is released and transported to the liver where it will undergo another transamination to generate pyruvate, which is used as a substrate for glucose production (gluconeogenesis). The glucose is released from the liver and oxidized by the skeletal muscle.', '31da73ee-240e-49ce-9d81-6f2223ca0127': 'The other key enzyme in nitrogen metabolism is glutaminase. Glutaminase, is active in the liver and responsible for deaminating glutamine as it is shuttled into the liver. The free ammonia can enter into the urea cycle, and the remaining glutamate can be transaminated to generate α-ketoglutarate. This is in contrast to glutamine synthetase, which is primarily used by peripheral tissues as a means of generating glutamine to remove ammonia from the tissues to the liver (figure 5.14). Nitrogen metabolism, unlike glucose metabolism, is fairly consistent in the fed and fasted states. Excess dietary amino acids, which are not stored, will also require deamination, and the carbons can be stored as either glycogen or fat.', 'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 5.16,cell_bio/images/Figure 5.16.jpg,Figure 5.16: Key regulatory step in the urea cycle. CPS1 is activated by N-acetylglutamate.,"This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.","{'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 5.3,cell_bio/images/Figure 5.3.jpg,Figure 5.3: Locations of amino acid and lactate entering gluconeogenesis as substrates for the pathway.,"Lactate is primarily produced through the Cori cycle or from anaerobic glucose oxidation. (Note: The Cori cycle, or lactic acid cycle, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscle or RBC travels to the liver and is converted to glucose. The glucose returns to the peripheral tissues and is metabolized back to lactate.) Once in the liver, lactate can be oxidized back to pyruvate through the reverse reaction catalyzed by lactate dehydrogenase (figure 5.3).","{'c827d3f2-88d2-4b93-9996-ea3bb4eb386e': 'Lactate is primarily produced through the Cori cycle or from anaerobic glucose oxidation. (Note: The Cori cycle, or lactic acid cycle, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscle or RBC travels to the liver and is converted to glucose. The glucose returns to the peripheral tissues and is metabolized back to lactate.)\xa0Once in the liver, lactate can be oxidized back to pyruvate through the reverse reaction catalyzed by lactate dehydrogenase (figure 5.3).', 'a1bd4d19-e758-479c-b85d-67408c03c539': 'Serum lactate levels may also be measured in conjunction with a complete metabolic panel. Serum lactate should be negligible under normal conditions, however, elevated lactate could be suggestive of excessive anaerobic metabolism, such as is the case in intense exercise or deficiency in oxygen transport caused by ischemic injury. This could also be caused by inappropriate diversion of substrate such as is the case in some enzymatic deficiencies (pyruvate dehydrogenase deficiency) or changes in NADH levels (figure 2.2).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', 'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 5.12,cell_bio/images/Figure 5.12.jpg,,Figure 5.12: Transamination reaction.,"{'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 5.13,cell_bio/images/Figure 5.13.jpg,,"Figure 5.13: Reactions catalyzed by glutamate dehydrogenase, glutaminase, and glutamine synthetase.","{'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 5.14,cell_bio/images/Figure 5.14.jpg,Figure 5.14: Movement of ammonia from peripheral tissues to the liver.,"In addition to transaminases, there are three other enzymes that play essential roles in nitrogen transport. Glutamate dehydrogenase (GDH) is present in most tissues and is one of the few enzymes able to fix or free ammonia. In figure 5.14, in the skeletal muscle, glutamate dehydrogenase is illustrated fixing ammonia to α-ketoglutarate to generate glutamate, while in the liver it is shown freeing ammonia in the reverse reaction. The direction of the reaction will be influenced by several factors including cellular needs, the levels of NAD+ or NADP+, and levels of ammonia (figure 5.14).","{'719c0809-1e48-4c89-aba5-84881dc6f07e': 'In addition to transaminases, there are three other enzymes that play essential roles in nitrogen transport. Glutamate dehydrogenase (GDH) is present in most tissues and is one of the few enzymes able to fix or free ammonia. In figure 5.14, in the skeletal muscle, glutamate dehydrogenase is illustrated fixing ammonia to α-ketoglutarate to generate glutamate, while in the liver it is shown freeing ammonia in the reverse reaction. The direction of the reaction will be influenced by several factors including cellular needs, the levels of NAD+ or NADP+, and levels of ammonia (figure 5.14).', '7c1ca1ac-8a56-4c9f-a40f-459b1c72a858': 'In peripheral tissues, glutamate generated from transamination or from the GDH reaction can be used to fix an additional ammonia to generate glutamine. This reaction, catalyzed by glutamine synthetase, facilitates the synthesis and subsequent movement of excess nitrogen from peripheral tissues to the liver (figure 5.14).', '4e735630-8767-4095-a6e4-f4e8ba10fa4f': 'In skeletal muscle, the alanine-glucose cycle is commonly used for the transport of nitrogen from the skeletal muscle to the liver. In this process, ammonia from amino acid degradation is transaminated to form glutamate. Alanine aminotransferase (AST) will transaminate glutamate with pyruvate to generate alanine (and α-ketoglutarate). The alanine is released and transported to the liver where it will undergo another transamination to generate pyruvate, which is used as a substrate for glucose production (gluconeogenesis). The glucose is released from the liver and oxidized by the skeletal muscle.', '31da73ee-240e-49ce-9d81-6f2223ca0127': 'The other key enzyme in nitrogen metabolism is glutaminase. Glutaminase, is active in the liver and responsible for deaminating glutamine as it is shuttled into the liver. The free ammonia can enter into the urea cycle, and the remaining glutamate can be transaminated to generate α-ketoglutarate. This is in contrast to glutamine synthetase, which is primarily used by peripheral tissues as a means of generating glutamine to remove ammonia from the tissues to the liver (figure 5.14). Nitrogen metabolism, unlike glucose metabolism, is fairly consistent in the fed and fasted states. Excess dietary amino acids, which are not stored, will also require deamination, and the carbons can be stored as either glycogen or fat.', 'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 5.15,cell_bio/images/Figure 5.15.jpg,,Figure 5.15: Overview of the urea cycle; the pathway spans both the mitochondria and cytosol.,"{'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 5.17,cell_bio/images/Figure 5.17.jpg,,Figure 5.17: Entry of the second nitrogen into the urea cycle; aspartate donates the second nitrogen for the synthesis of urea.,"{'e6e4c0fb-98e1-4c65-9504-bf6a798c0c1f': 'This pathway is predominantly regulated at one key enzyme, carbamoyl phosphate synthetase 1 (figure 5.16). This enzyme requires N-acetylglutamate (NAGS) as an allosteric activator. The synthesis of NAGS is enhanced by arginine, which is an intermediate of the urea cycle. Therefore the cycle provides positive feedback on itself. As flux through the urea cycle increases, and synthesis of arginine increases, this will enhance NAGS production and increase synthesis of carbamoyl phosphate.', '9a2e40ed-8b34-45e2-ab61-0a9bc350f30e': 'Unlike the other pathways discussed, the urea cycle functions independent of hormonal control as it functions to dispose of nitrogen either from excess dietary sources or from protein catabolism/turnover. In the fasted state this is especially important as the carbon skeletons produced are required as substrates for gluconeogenesis (see figure 5.3). In the fed state, amino acids can be deaminated and contribute to the carbon pool (see figures 4.12 and 4.13).', '4b51e50f-78a0-40f4-b2cf-bc492b0a6480': 'In summary, the process of nitrogen movement from the peripheral tissues to the liver is essential. It involves transamination reactions to produce alanine, and the synthesis of glutamine (by glutamine synthetase) to generate two nontoxic carriers of ammonia. Once transported to the liver, again, transamination coupled with the reactions of glutaminase and glutamate dehydrogenase will allow for ammonia to be freed and enter into the urea cycle.', 'f45b82f5-1883-4805-9438-447c72ff08c2': 'Table 5.3: Summary of pathway regulation.', '77c037e3-9cea-4d8c-a377-442839103abc': '5.3 References and resources'}"
Figure 4.1,cell_bio/images/Figure 4.1.jpg,"Figure 4.1: Summary of glycolysis. The three regulated steps of the process will be the focus, and those are catalyzed by the enzymes glucokinase/hexokinase, phosphofructokinase 1 (PFK1), and pyruvate kinase. All other steps in glycolysis are reversible (as indicated by the arrows) and are also used in gluconeogenesis.","Like glycolysis, there is an additional regulation here by the bifunctional enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase (figure 4.1). This bifunctional enzyme functions as a kinase in the fed state (PFK2) and generates fructose 2,6-bisphosphate that allosterically activates PFK1. In the fasted state the enzyme is phosphorylated by glucagon-activated protein kinase A, and this actives the phosphatase activity of the enzyme. The enzyme dephosphorylates fructose 2,6-bisphosphate and therefore reduces the allosteric activation of PFK1 facilitating the reverse reaction by fructose 1,6-bisphosphatase (figure 5.2).","{'12c5c357-49fb-4f02-8d67-cf4e9a649d4b': 'As PEP continues through the reverse of glycolysis, fructose 1,6-bisphosphate is generated. To bypass the irreversible step catalyzed by phosphofructokinase 1 (PFK1) in glycolysis, the enzyme fructose 1,6-bisphosphatase (FBP1) is present and dephosphorylates fructose 1,6-bisphosphate to produce fructose 6-phosphate. This enzyme, FBP1, is inhibited by AMP and fructose 2,6-bisphosphate (figure 5.2).', 'a9b7cea1-4ae3-4760-b736-cbe9e0e7eaa4': 'Like glycolysis, there is an additional regulation here by the bifunctional enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase (figure 4.1). This bifunctional enzyme functions as a kinase in the fed state (PFK2) and generates fructose 2,6-bisphosphate that allosterically activates PFK1. In the fasted state the enzyme is phosphorylated by glucagon-activated protein kinase A, and this actives the phosphatase activity of the enzyme. The enzyme dephosphorylates fructose 2,6-bisphosphate and therefore reduces the allosteric activation of PFK1 facilitating the reverse reaction by fructose 1,6-bisphosphatase (figure 5.2).', 'afd375b8-13ae-4f33-9191-ec36c46ba669': 'Glycolysis in the liver has three primary regulated and irreversible steps (figure 4.1).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.2,cell_bio/images/Figure 4.2.jpg,"Figure 4.2: Regulatory step committed by hexo or glucokinase. The first regulatory step in glycolysis is the phosphorylation of glucose by hexo or glucokinase. The reverse reaction, which is part of gluconeogensis, is catalyzed by glucose 6-phosphatase.","In the liver, glucose is taken up through an insulin-independent process mediated by GLUT2 transporters. Following this, glucose must be phosphorylated to be trapped in the cell. The phosphorylation of glucose to glucose 6-phosphate is catalyzed by glucokinase (figure 4.2) in the liver.","{'4c99a8ba-f5ca-4834-83cf-d7ffb0fee66e': 'In the liver, glucose is taken up through an insulin-independent process mediated by GLUT2 transporters. Following this, glucose must be phosphorylated to be trapped in the cell. The phosphorylation of glucose to glucose 6-phosphate is catalyzed by glucokinase (figure 4.2) in the liver.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.3,cell_bio/images/Figure 4.3.jpg,Figure 4.3: Comparison of glucokinase and hexokinase kinetics.,"Glucokinase and hexokinase perform the same reaction but have very different enzyme kinetics. Glucokinase (in the liver) has a higher Km (lower affinity for glucose) when compared to hexokinase. In the liver, this enzyme will phosphorylate glucose only when glucose concentrations are high such as in the fed state. Glucokinase also has a high Vmax and is therefore not rapidly saturated. This allows for continuous glucose uptake when glucose levels are high allowing for glucose storage and the rapid removal of glucose from circulation, minimizing the likelihood of hyperglycemia. In contrast, hexokinase has a lower Km and a high affinity for glucose (figure 4.3). This enzyme becomes rapidly saturated over a very small range of glucose concentrations.","{'52cd4589-a316-49e0-9233-fe727bcaedf3': 'In skeletal muscle, and most other peripheral tissues, glucose is phosphorylated by hexokinase.', 'a74a413e-d043-440b-ad55-229a7622957c': 'Glucokinase and hexokinase perform the same reaction but have very different enzyme kinetics. Glucokinase (in the liver) has a higher Km (lower affinity for glucose) when compared to hexokinase. In the liver, this enzyme will phosphorylate glucose only when glucose concentrations are high such as in the fed state. Glucokinase also has a high Vmax and is therefore not rapidly saturated. This allows for continuous glucose uptake when glucose levels are high allowing for glucose storage and the rapid removal of glucose from circulation, minimizing the likelihood of hyperglycemia. In contrast, hexokinase has a lower Km and a high affinity for glucose (figure 4.3). This enzyme becomes rapidly saturated over a very small range of glucose concentrations.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.4,cell_bio/images/Figure 4.4.jpg,Figure 4.4: Regulation of glucokinase by glucokinase regulatory protein.,"Hexokinase is regulated through feedback inhibition where glucose 6-phosphate will compete with glucose for substrate binding. On the other hand, glucokinase is regulated through an alternative mechanism involving the glucokinase regulatory binding protein (GKRP). This protein will bind glucokinase and trap it in the nucleus. When glucose is high, glucokinase is released into the cytosol to phosphorylate glucose. As fructose 6-phosphate levels increase, this will inhibit the glucokinase reaction by enhancing the rebinding of glucokinase to GKRP, trapping it in the nucleus (figure 4.4).","{'ba90fa8f-51ce-44e5-b2eb-208e7863f8fe': 'Hexokinase is regulated through feedback inhibition where glucose 6-phosphate will compete with glucose for substrate binding. On the other hand, glucokinase is regulated through an alternative mechanism involving the glucokinase regulatory binding protein (GKRP). This protein will bind glucokinase and trap it in the nucleus. When glucose is high, glucokinase is released into the cytosol to phosphorylate glucose. As fructose 6-phosphate levels increase, this will inhibit the glucokinase reaction by enhancing the rebinding of glucokinase to GKRP, trapping it in the nucleus (figure 4.4).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.5,cell_bio/images/Figure 4.5.jpg,"Figure 4.5: Regulation of PFK1 by fructose 2,6-bisphosphate generated by PFK2.","Fructose 2,6-bisphosphate is an important regulator of glycolysis, formed by a shunt in the glycolytic pathway. When there is an excess of fructose 6-phosphate in the cell, this substrate is accepted by phosphofructokinase 2 (PFK2) and converted to fructose 2,6-bisphosphate. This compound, fructose 2,6-bisphosphate, functions as an allosteric activator of PFK1. Additionally, PFK2 can be regulated by covalent modification such as phosphorylation. PFK2 is a bifunctional enzyme and only functions as a kinase when insulin is high and it is dephosphorylated. Under fasted conditions, when glucagon is high, this leads to the phosphorylation and inactivation of PFK2; when the enzyme is phosphorylated, it functions as a phosphatase and is referred to as fructose 2,6-bisphosphatase (FBP2) (figure 4.5).","{'fdacf8fe-f3db-456f-8667-54e2a70e5232': 'Regulation of phosphofructokinase 1 is primarily through allosteric activation by AMP and fructose 2,6-bisphosphate. High AMP levels would indicate a lack of energy within the cell, and this would increase flux through glycolysis by enhancing the activity of PFK1. PFK1 is also inhibited by citrate and ATP; levels of these compounds are indicative of a high energy state, suggesting there are sufficient oxidation productions and glucose is diverted to storage pathways.', '71cbabba-acd0-4808-a451-a5ac34d45271': 'Fructose 2,6-bisphosphate is an important regulator of glycolysis, formed by a shunt in the glycolytic pathway. When there is an excess of fructose 6-phosphate in the cell, this substrate is accepted by phosphofructokinase 2 (PFK2) and converted to fructose 2,6-bisphosphate. This compound, fructose 2,6-bisphosphate, functions as an allosteric activator of PFK1. Additionally, PFK2 can be regulated by covalent modification such as phosphorylation. PFK2 is a bifunctional enzyme and only functions as a kinase when insulin is high and it is dephosphorylated. Under fasted conditions, when glucagon is high, this leads to the phosphorylation and inactivation of PFK2;\xa0when the enzyme is phosphorylated, it functions as a phosphatase and is referred to as fructose 2,6-bisphosphatase (FBP2) (figure 4.5).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.6,cell_bio/images/Figure 4.6.jpg,"Figure 4.6: Regulation of pyruvate kinase phosphorylation and fructose 1,6-bisphosphate.","The final regulatory step of glycolysis is the reaction catalyzed by pyruvate kinase. The enzyme converts phosphoenol pyruvate (PEP) to pyruvate. PK can be regulated by phosphorylation and allosteric means. PK is subject to feed-forward activation by fructose 1,6-bisphosphate, which allosterically activates the enzyme, increasing flux in the downward direction. As energy levels in the cell increase, ATP levels will reduce enzyme activity through allosteric inhibition (figure 4.6). PK can also be regulated through phosphorylation. Similar to PFK2, PK is dephosphorylated and active in the fed state but phosphorylated during the fasted state, which renders the enzyme inactive; the phosphorylation is glucagon mediated.","{'ac905808-95b6-434a-9a70-8656cdb678a3': 'The final regulatory step of glycolysis is the reaction catalyzed by pyruvate kinase. The enzyme converts phosphoenol pyruvate (PEP) to pyruvate. PK can be regulated by phosphorylation and allosteric means. PK is subject to feed-forward activation by fructose 1,6-bisphosphate, which allosterically activates the enzyme, increasing flux in the downward direction. As energy levels in the cell increase, ATP levels will reduce enzyme activity through allosteric inhibition (figure 4.6). PK can also be regulated through phosphorylation. Similar to PFK2, PK is dephosphorylated and active in the fed state but phosphorylated during the fasted state, which renders the enzyme inactive; the phosphorylation is glucagon mediated.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.7,cell_bio/images/Figure 4.7.jpg,Figure 4.7: Glycerol 3-phosphate shuttle.,"The glycerol 3-phosphate shuttle is the major shuttle used in most tissues to move NADH from the cytosol to the mitochondria for oxidation. In this pathway, NAD+ is regenerated by glycerol 3-phosphate dehydrogenase, which transfers electrons from NADH to dihydroxyacetonephosphate to generate glycerol 3-phosphate. Glycerol 3-phosphate can diffuse across the mitochondrial membrane where it will donate electrons to membrane bound FAD (bound to succinate dehydrogenase) (figure 4.7).","{'17aa2606-72d4-4e61-9e35-9819dbee0be4': 'The glycerol 3-phosphate shuttle is the major shuttle used in most tissues to move NADH from the cytosol to the mitochondria for oxidation. In this pathway, NAD+ is regenerated by glycerol 3-phosphate dehydrogenase, which transfers electrons from NADH to dihydroxyacetonephosphate to generate glycerol 3-phosphate. Glycerol 3-phosphate can diffuse across the mitochondrial membrane where it will donate electrons to membrane bound FAD (bound to succinate dehydrogenase) (figure 4.7).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.8,cell_bio/images/Figure 4.8.jpg,Figure 4.8: Malate-aspartate shuttle.,"Many tissues also contain the malate-aspartate shuttle, which can also carry cytosolic NADH into the mitochondria. Cytosolic NADH is used to reduce oxaloacetate (OAA) to malate, which can cross the mitochondrial membrane. Once inside the mitochondria, malate can be oxidized to OAA to produce NADH. OAA canʼt pass through the mitochondrial membrane, so it requires transamination to aspartate, which can be shuttled into the cytosol to regenerate the cycle (figure 4.8).","{'7b9ae9f5-ccb1-4f7b-bbb3-7d299dd10b23': 'Many tissues also contain the malate-aspartate shuttle, which can also carry cytosolic NADH into the mitochondria. Cytosolic NADH is used to reduce oxaloacetate (OAA) to malate, which can cross the mitochondrial membrane. Once inside the mitochondria, malate can be oxidized to OAA to produce NADH. OAA canʼt pass through the mitochondrial membrane, so it requires transamination to aspartate, which can be shuttled into the cytosol to regenerate the cycle (figure 4.8).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.9,cell_bio/images/Figure 4.9.jpg,Figure 4.9: Regulation of the pyruvate dehydrogenase complex (PDC).,The enzyme responsible for phosphorylation of the PDC is pyruvate dehydrogenase kinase. The kinase is regulated inversely to the PDC (figure 4.9). The kinase is most active when acetyl-CoA and NADH are high. These compounds will stimulate the kinase to phosphorylate and inactivate the PDC. The PDC can be dephosphorylated by a calcium-mediated phosphatase.,"{'833f75de-e02a-4897-8a04-a84f27f22f99': 'The PDC is regulated by allosteric and covalent regulations. The complex itself can be allosterically activated by pyruvate and NAD+. Elevation of substrate (pyruvate) will enhance flux through this enzyme as will the indication of low energy states as triggered by high NAD+ levels. The PDC is also inhibited by acetyl-CoA and NADH directly. Product inhibition is a very common regulatory mechanism,\xa0and high NADH would signal sufficient energy levels, therefore decreasing activity of the PDC.', '7467b7b5-2f7c-42c8-b0f4-f7e7867d3606': 'The PDC is also regulated through covalent modification. Phosphorylation of the complex will decrease activity of the enzyme.', 'e0994ed2-87b2-42fd-886b-4fdc72e9ba7e': 'The enzyme responsible for phosphorylation of the PDC is pyruvate dehydrogenase kinase. The kinase is regulated inversely to the PDC (figure 4.9). The kinase is most active when acetyl-CoA and NADH are high. These compounds will stimulate the kinase to phosphorylate and inactivate the PDC. The PDC can be dephosphorylated by a calcium-mediated phosphatase.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.1,cell_bio/images/Figure 4.1.jpg,"Figure 4.1: Summary of glycolysis. The three regulated steps of the process will be the focus, and those are catalyzed by the enzymes glucokinase/hexokinase, phosphofructokinase 1 (PFK1), and pyruvate kinase. All other steps in glycolysis are reversible (as indicated by the arrows) and are also used in gluconeogenesis.","Like glycolysis, there is an additional regulation here by the bifunctional enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase (figure 4.1). This bifunctional enzyme functions as a kinase in the fed state (PFK2) and generates fructose 2,6-bisphosphate that allosterically activates PFK1. In the fasted state the enzyme is phosphorylated by glucagon-activated protein kinase A, and this actives the phosphatase activity of the enzyme. The enzyme dephosphorylates fructose 2,6-bisphosphate and therefore reduces the allosteric activation of PFK1 facilitating the reverse reaction by fructose 1,6-bisphosphatase (figure 5.2).","{'12c5c357-49fb-4f02-8d67-cf4e9a649d4b': 'As PEP continues through the reverse of glycolysis, fructose 1,6-bisphosphate is generated. To bypass the irreversible step catalyzed by phosphofructokinase 1 (PFK1) in glycolysis, the enzyme fructose 1,6-bisphosphatase (FBP1) is present and dephosphorylates fructose 1,6-bisphosphate to produce fructose 6-phosphate. This enzyme, FBP1, is inhibited by AMP and fructose 2,6-bisphosphate (figure 5.2).', 'a9b7cea1-4ae3-4760-b736-cbe9e0e7eaa4': 'Like glycolysis, there is an additional regulation here by the bifunctional enzyme phosphofructokinase 2 (PFK2)/fructose 2,6-bisphosphatase (figure 4.1). This bifunctional enzyme functions as a kinase in the fed state (PFK2) and generates fructose 2,6-bisphosphate that allosterically activates PFK1. In the fasted state the enzyme is phosphorylated by glucagon-activated protein kinase A, and this actives the phosphatase activity of the enzyme. The enzyme dephosphorylates fructose 2,6-bisphosphate and therefore reduces the allosteric activation of PFK1 facilitating the reverse reaction by fructose 1,6-bisphosphatase (figure 5.2).', 'afd375b8-13ae-4f33-9191-ec36c46ba669': 'Glycolysis in the liver has three primary regulated and irreversible steps (figure 4.1).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.2,cell_bio/images/Figure 4.2.jpg,"Figure 4.2: Regulatory step committed by hexo or glucokinase. The first regulatory step in glycolysis is the phosphorylation of glucose by hexo or glucokinase. The reverse reaction, which is part of gluconeogensis, is catalyzed by glucose 6-phosphatase.","In the liver, glucose is taken up through an insulin-independent process mediated by GLUT2 transporters. Following this, glucose must be phosphorylated to be trapped in the cell. The phosphorylation of glucose to glucose 6-phosphate is catalyzed by glucokinase (figure 4.2) in the liver.","{'4c99a8ba-f5ca-4834-83cf-d7ffb0fee66e': 'In the liver, glucose is taken up through an insulin-independent process mediated by GLUT2 transporters. Following this, glucose must be phosphorylated to be trapped in the cell. The phosphorylation of glucose to glucose 6-phosphate is catalyzed by glucokinase (figure 4.2) in the liver.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.3,cell_bio/images/Figure 4.3.jpg,Figure 4.3: Comparison of glucokinase and hexokinase kinetics.,"Glucokinase and hexokinase perform the same reaction but have very different enzyme kinetics. Glucokinase (in the liver) has a higher Km (lower affinity for glucose) when compared to hexokinase. In the liver, this enzyme will phosphorylate glucose only when glucose concentrations are high such as in the fed state. Glucokinase also has a high Vmax and is therefore not rapidly saturated. This allows for continuous glucose uptake when glucose levels are high allowing for glucose storage and the rapid removal of glucose from circulation, minimizing the likelihood of hyperglycemia. In contrast, hexokinase has a lower Km and a high affinity for glucose (figure 4.3). This enzyme becomes rapidly saturated over a very small range of glucose concentrations.","{'52cd4589-a316-49e0-9233-fe727bcaedf3': 'In skeletal muscle, and most other peripheral tissues, glucose is phosphorylated by hexokinase.', 'a74a413e-d043-440b-ad55-229a7622957c': 'Glucokinase and hexokinase perform the same reaction but have very different enzyme kinetics. Glucokinase (in the liver) has a higher Km (lower affinity for glucose) when compared to hexokinase. In the liver, this enzyme will phosphorylate glucose only when glucose concentrations are high such as in the fed state. Glucokinase also has a high Vmax and is therefore not rapidly saturated. This allows for continuous glucose uptake when glucose levels are high allowing for glucose storage and the rapid removal of glucose from circulation, minimizing the likelihood of hyperglycemia. In contrast, hexokinase has a lower Km and a high affinity for glucose (figure 4.3). This enzyme becomes rapidly saturated over a very small range of glucose concentrations.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.4,cell_bio/images/Figure 4.4.jpg,Figure 4.4: Regulation of glucokinase by glucokinase regulatory protein.,"Hexokinase is regulated through feedback inhibition where glucose 6-phosphate will compete with glucose for substrate binding. On the other hand, glucokinase is regulated through an alternative mechanism involving the glucokinase regulatory binding protein (GKRP). This protein will bind glucokinase and trap it in the nucleus. When glucose is high, glucokinase is released into the cytosol to phosphorylate glucose. As fructose 6-phosphate levels increase, this will inhibit the glucokinase reaction by enhancing the rebinding of glucokinase to GKRP, trapping it in the nucleus (figure 4.4).","{'ba90fa8f-51ce-44e5-b2eb-208e7863f8fe': 'Hexokinase is regulated through feedback inhibition where glucose 6-phosphate will compete with glucose for substrate binding. On the other hand, glucokinase is regulated through an alternative mechanism involving the glucokinase regulatory binding protein (GKRP). This protein will bind glucokinase and trap it in the nucleus. When glucose is high, glucokinase is released into the cytosol to phosphorylate glucose. As fructose 6-phosphate levels increase, this will inhibit the glucokinase reaction by enhancing the rebinding of glucokinase to GKRP, trapping it in the nucleus (figure 4.4).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.5,cell_bio/images/Figure 4.5.jpg,"Figure 4.5: Regulation of PFK1 by fructose 2,6-bisphosphate generated by PFK2.","Fructose 2,6-bisphosphate is an important regulator of glycolysis, formed by a shunt in the glycolytic pathway. When there is an excess of fructose 6-phosphate in the cell, this substrate is accepted by phosphofructokinase 2 (PFK2) and converted to fructose 2,6-bisphosphate. This compound, fructose 2,6-bisphosphate, functions as an allosteric activator of PFK1. Additionally, PFK2 can be regulated by covalent modification such as phosphorylation. PFK2 is a bifunctional enzyme and only functions as a kinase when insulin is high and it is dephosphorylated. Under fasted conditions, when glucagon is high, this leads to the phosphorylation and inactivation of PFK2; when the enzyme is phosphorylated, it functions as a phosphatase and is referred to as fructose 2,6-bisphosphatase (FBP2) (figure 4.5).","{'fdacf8fe-f3db-456f-8667-54e2a70e5232': 'Regulation of phosphofructokinase 1 is primarily through allosteric activation by AMP and fructose 2,6-bisphosphate. High AMP levels would indicate a lack of energy within the cell, and this would increase flux through glycolysis by enhancing the activity of PFK1. PFK1 is also inhibited by citrate and ATP; levels of these compounds are indicative of a high energy state, suggesting there are sufficient oxidation productions and glucose is diverted to storage pathways.', '71cbabba-acd0-4808-a451-a5ac34d45271': 'Fructose 2,6-bisphosphate is an important regulator of glycolysis, formed by a shunt in the glycolytic pathway. When there is an excess of fructose 6-phosphate in the cell, this substrate is accepted by phosphofructokinase 2 (PFK2) and converted to fructose 2,6-bisphosphate. This compound, fructose 2,6-bisphosphate, functions as an allosteric activator of PFK1. Additionally, PFK2 can be regulated by covalent modification such as phosphorylation. PFK2 is a bifunctional enzyme and only functions as a kinase when insulin is high and it is dephosphorylated. Under fasted conditions, when glucagon is high, this leads to the phosphorylation and inactivation of PFK2;\xa0when the enzyme is phosphorylated, it functions as a phosphatase and is referred to as fructose 2,6-bisphosphatase (FBP2) (figure 4.5).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.6,cell_bio/images/Figure 4.6.jpg,"Figure 4.6: Regulation of pyruvate kinase phosphorylation and fructose 1,6-bisphosphate.","The final regulatory step of glycolysis is the reaction catalyzed by pyruvate kinase. The enzyme converts phosphoenol pyruvate (PEP) to pyruvate. PK can be regulated by phosphorylation and allosteric means. PK is subject to feed-forward activation by fructose 1,6-bisphosphate, which allosterically activates the enzyme, increasing flux in the downward direction. As energy levels in the cell increase, ATP levels will reduce enzyme activity through allosteric inhibition (figure 4.6). PK can also be regulated through phosphorylation. Similar to PFK2, PK is dephosphorylated and active in the fed state but phosphorylated during the fasted state, which renders the enzyme inactive; the phosphorylation is glucagon mediated.","{'ac905808-95b6-434a-9a70-8656cdb678a3': 'The final regulatory step of glycolysis is the reaction catalyzed by pyruvate kinase. The enzyme converts phosphoenol pyruvate (PEP) to pyruvate. PK can be regulated by phosphorylation and allosteric means. PK is subject to feed-forward activation by fructose 1,6-bisphosphate, which allosterically activates the enzyme, increasing flux in the downward direction. As energy levels in the cell increase, ATP levels will reduce enzyme activity through allosteric inhibition (figure 4.6). PK can also be regulated through phosphorylation. Similar to PFK2, PK is dephosphorylated and active in the fed state but phosphorylated during the fasted state, which renders the enzyme inactive; the phosphorylation is glucagon mediated.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.7,cell_bio/images/Figure 4.7.jpg,Figure 4.7: Glycerol 3-phosphate shuttle.,"The glycerol 3-phosphate shuttle is the major shuttle used in most tissues to move NADH from the cytosol to the mitochondria for oxidation. In this pathway, NAD+ is regenerated by glycerol 3-phosphate dehydrogenase, which transfers electrons from NADH to dihydroxyacetonephosphate to generate glycerol 3-phosphate. Glycerol 3-phosphate can diffuse across the mitochondrial membrane where it will donate electrons to membrane bound FAD (bound to succinate dehydrogenase) (figure 4.7).","{'17aa2606-72d4-4e61-9e35-9819dbee0be4': 'The glycerol 3-phosphate shuttle is the major shuttle used in most tissues to move NADH from the cytosol to the mitochondria for oxidation. In this pathway, NAD+ is regenerated by glycerol 3-phosphate dehydrogenase, which transfers electrons from NADH to dihydroxyacetonephosphate to generate glycerol 3-phosphate. Glycerol 3-phosphate can diffuse across the mitochondrial membrane where it will donate electrons to membrane bound FAD (bound to succinate dehydrogenase) (figure 4.7).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.8,cell_bio/images/Figure 4.8.jpg,Figure 4.8: Malate-aspartate shuttle.,"Many tissues also contain the malate-aspartate shuttle, which can also carry cytosolic NADH into the mitochondria. Cytosolic NADH is used to reduce oxaloacetate (OAA) to malate, which can cross the mitochondrial membrane. Once inside the mitochondria, malate can be oxidized to OAA to produce NADH. OAA canʼt pass through the mitochondrial membrane, so it requires transamination to aspartate, which can be shuttled into the cytosol to regenerate the cycle (figure 4.8).","{'7b9ae9f5-ccb1-4f7b-bbb3-7d299dd10b23': 'Many tissues also contain the malate-aspartate shuttle, which can also carry cytosolic NADH into the mitochondria. Cytosolic NADH is used to reduce oxaloacetate (OAA) to malate, which can cross the mitochondrial membrane. Once inside the mitochondria, malate can be oxidized to OAA to produce NADH. OAA canʼt pass through the mitochondrial membrane, so it requires transamination to aspartate, which can be shuttled into the cytosol to regenerate the cycle (figure 4.8).', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.9,cell_bio/images/Figure 4.9.jpg,Figure 4.9: Regulation of the pyruvate dehydrogenase complex (PDC).,The enzyme responsible for phosphorylation of the PDC is pyruvate dehydrogenase kinase. The kinase is regulated inversely to the PDC (figure 4.9). The kinase is most active when acetyl-CoA and NADH are high. These compounds will stimulate the kinase to phosphorylate and inactivate the PDC. The PDC can be dephosphorylated by a calcium-mediated phosphatase.,"{'833f75de-e02a-4897-8a04-a84f27f22f99': 'The PDC is regulated by allosteric and covalent regulations. The complex itself can be allosterically activated by pyruvate and NAD+. Elevation of substrate (pyruvate) will enhance flux through this enzyme as will the indication of low energy states as triggered by high NAD+ levels. The PDC is also inhibited by acetyl-CoA and NADH directly. Product inhibition is a very common regulatory mechanism,\xa0and high NADH would signal sufficient energy levels, therefore decreasing activity of the PDC.', '7467b7b5-2f7c-42c8-b0f4-f7e7867d3606': 'The PDC is also regulated through covalent modification. Phosphorylation of the complex will decrease activity of the enzyme.', 'e0994ed2-87b2-42fd-886b-4fdc72e9ba7e': 'The enzyme responsible for phosphorylation of the PDC is pyruvate dehydrogenase kinase. The kinase is regulated inversely to the PDC (figure 4.9). The kinase is most active when acetyl-CoA and NADH are high. These compounds will stimulate the kinase to phosphorylate and inactivate the PDC. The PDC can be dephosphorylated by a calcium-mediated phosphatase.', 'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).'}"
Figure 4.10,cell_bio/images/Figure 4.10.jpg,Figure 4.10: Overview of the TCA cycle.,"The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).","{'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', 'bcba9f79-02f4-4bd8-af3b-68761776a585': 'Likewise, α-ketoglutarate dehydrogenase can be activated by Ca2+ and inhibited by NADH (and succinyl-CoA) (figure 4.13).', '0674e92c-bf8b-44e0-93a6-1ff984cea24c': 'Malate dehydrogenase can also be inhibited by NADH, however, the reaction is reversible depending on levels of NADH. The oxidation of malate to OAA requires NAD+, and under certain pathological situations the lack of free NAD+ within the mitochondria will reduce the rate of this reaction (this is common in\xa0the case of alcohol metabolism).', '769e382b-4493-4957-bd34-61228dcc16eb': 'Keep in mind that with the addition of each acetyl-CoA (comprised of 2 carbons) to the TCA cycle, two molecules of CO2 are released, thus there is no net gain or loss of carbons in the cycle. The process moves forward driven by energetics and substrate availability. The pathway can be active in both the fed and fasted states. In the fed state, acetyl-CoA is generated primarily through glucose oxidation. In contrast, in the fasted state acetyl-CoA is generated primarily from β-oxidation, and the majority of acetyl-CoA is used to synthesize ketones.', 'bbe38e2f-4233-4123-ad47-00967f8b2d53': 'Table 4.2: Summary of pathway regulation.', 'a0f3960c-37d6-4a27-8622-1dc59b59df98': '4.2 References and resources', '56280a32-2096-4292-b0e3-d81d7a1b5bdf': 'Lieberman M, Peet A. Figure 4.12 Anaplerotic reactions of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 473. Figure 23.18 Major anaplerotic pathways of the tricarboxylic acid (TCA) cycle. 2017.', '43c2a05d-f08c-4ef1-93e3-cc3a9d4e31be': 'Lieberman M, Peet A. Figure 4.13 Regulation of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 468. Figure 23.11 Major regulatory interaction in the tricarboxylic acid (TCA) cycle. 2017. Added ion channel by Léa Lortal from the Noun Project.', 'a20c5f37-73c1-4597-85fc-15ca116b23fd': '4.3 Electron Transport Chain (ETC)', '27b219b9-971b-4a3e-a1ca-6627180e7ddc': 'In the production of NADH and FADH2 by the TCA cycle, β-oxidation or glycolysis is funneled directly into the electron transport chain (ETC) where each of these reduced coenzymes will donate two electrons to electron carriers. As the electrons are passed down their oxidation gradient, some of the energy is lost, but much of this energy is used to pump protons into the intermembrane space of the mitochondria.', 'b786884b-a1de-4583-93be-18ced847fd32': 'The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).', 'bad771c1-d83d-41ca-8988-296308499c6f': 'There are site specific inhibitors of the ETC to be aware of, and these will disrupt electron flow reducing overall ATP production.'}"
Figure 4.11,cell_bio/images/Figure 4.11.jpg,Figure 4.11: Substrates produced by the TCA cycle.,"The other major role of the TCA cycle is to provide substrates for other synthetic pathways. Malate is shuttled out of the TCA cycle and used as a substrate for gluconeogenesis and oxaloacetate (OAA) and α-ketoglutarate are used as substrates for amino acid synthesis. Through transamination reactions, these two keto-acids can be converted into aspartate and glutamate, respectively. α-ketoglutarate is also a key substrate for the synthesis of neurotransmitters, and succinyl-CoA is the substrate for heme synthesis. Citrate is also a key compound as it is both an intermediate of the TCA cycle and can be shuttled into the cytosol to provide acetyl-CoA for both cholesterol and fatty acid synthesis (figure 4.11).","{'642ae580-8500-4860-b02c-2cba56add6cc': 'The other major role of the TCA cycle is to provide substrates for other synthetic pathways. Malate is shuttled out of the TCA cycle and used as a substrate for gluconeogenesis and\xa0oxaloacetate (OAA) and α-ketoglutarate are used as substrates for amino acid synthesis. Through transamination reactions, these two keto-acids can be converted into aspartate and glutamate, respectively. α-ketoglutarate is also a key substrate for the synthesis of neurotransmitters, and succinyl-CoA is the substrate for heme synthesis. Citrate is also a key compound as it is both an intermediate of the TCA cycle and can be shuttled into the cytosol to provide acetyl-CoA for both cholesterol and fatty acid synthesis (figure 4.11).', 'a8a38913-a371-48ab-844a-47cc69e6476b': 'In order to maintain a pool of TCA cycle intermediates, as substrates are removed from the cycle, there are\xa0several key reactions (anaplerotic reactions) that\xa0are responsible for the addition of intermediates. These reactions are illustrated in figure 4.12. Notice all of these reactions add carbon back to the cycle from amino acids (reactions 1, 2, 3, 4, 5). These will become very important in the discussion of gluconeogenesis where these substrates will provide the majority of carbon for glucose production. Odd chain fatty acid oxidation can also provide carbon in the from of propionyl-CoA (3) although this is not a primary source of TCA cycle intermediates.', 'bcba9f79-02f4-4bd8-af3b-68761776a585': 'Likewise, α-ketoglutarate dehydrogenase can be activated by Ca2+ and inhibited by NADH (and succinyl-CoA) (figure 4.13).', '0674e92c-bf8b-44e0-93a6-1ff984cea24c': 'Malate dehydrogenase can also be inhibited by NADH, however, the reaction is reversible depending on levels of NADH. The oxidation of malate to OAA requires NAD+, and under certain pathological situations the lack of free NAD+ within the mitochondria will reduce the rate of this reaction (this is common in\xa0the case of alcohol metabolism).', '769e382b-4493-4957-bd34-61228dcc16eb': 'Keep in mind that with the addition of each acetyl-CoA (comprised of 2 carbons) to the TCA cycle, two molecules of CO2 are released, thus there is no net gain or loss of carbons in the cycle. The process moves forward driven by energetics and substrate availability. The pathway can be active in both the fed and fasted states. In the fed state, acetyl-CoA is generated primarily through glucose oxidation. In contrast, in the fasted state acetyl-CoA is generated primarily from β-oxidation, and the majority of acetyl-CoA is used to synthesize ketones.', 'bbe38e2f-4233-4123-ad47-00967f8b2d53': 'Table 4.2: Summary of pathway regulation.', 'a0f3960c-37d6-4a27-8622-1dc59b59df98': '4.2 References and resources', '56280a32-2096-4292-b0e3-d81d7a1b5bdf': 'Lieberman M, Peet A. Figure 4.12 Anaplerotic reactions of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 473. Figure 23.18 Major anaplerotic pathways of the tricarboxylic acid (TCA) cycle. 2017.', '43c2a05d-f08c-4ef1-93e3-cc3a9d4e31be': 'Lieberman M, Peet A. Figure 4.13 Regulation of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 468. Figure 23.11 Major regulatory interaction in the tricarboxylic acid (TCA) cycle. 2017. Added ion channel by Léa Lortal from the Noun Project.', 'a20c5f37-73c1-4597-85fc-15ca116b23fd': '4.3 Electron Transport Chain (ETC)', '27b219b9-971b-4a3e-a1ca-6627180e7ddc': 'In the production of NADH and FADH2 by the TCA cycle, β-oxidation or glycolysis is funneled directly into the electron transport chain (ETC) where each of these reduced coenzymes will donate two electrons to electron carriers. As the electrons are passed down their oxidation gradient, some of the energy is lost, but much of this energy is used to pump protons into the intermembrane space of the mitochondria.', 'b786884b-a1de-4583-93be-18ced847fd32': 'The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).', 'bad771c1-d83d-41ca-8988-296308499c6f': 'There are site specific inhibitors of the ETC to be aware of, and these will disrupt electron flow reducing overall ATP production.'}"
Figure 4.12,cell_bio/images/Figure 4.12.jpg,Figure 4.12: Anaplerotic reactions of the TCA cycle.,"In order to maintain a pool of TCA cycle intermediates, as substrates are removed from the cycle, there are several key reactions (anaplerotic reactions) that are responsible for the addition of intermediates. These reactions are illustrated in figure 4.12. Notice all of these reactions add carbon back to the cycle from amino acids (reactions 1, 2, 3, 4, 5). These will become very important in the discussion of gluconeogenesis where these substrates will provide the majority of carbon for glucose production. Odd chain fatty acid oxidation can also provide carbon in the from of propionyl-CoA (3) although this is not a primary source of TCA cycle intermediates.","{'642ae580-8500-4860-b02c-2cba56add6cc': 'The other major role of the TCA cycle is to provide substrates for other synthetic pathways. Malate is shuttled out of the TCA cycle and used as a substrate for gluconeogenesis and\xa0oxaloacetate (OAA) and α-ketoglutarate are used as substrates for amino acid synthesis. Through transamination reactions, these two keto-acids can be converted into aspartate and glutamate, respectively. α-ketoglutarate is also a key substrate for the synthesis of neurotransmitters, and succinyl-CoA is the substrate for heme synthesis. Citrate is also a key compound as it is both an intermediate of the TCA cycle and can be shuttled into the cytosol to provide acetyl-CoA for both cholesterol and fatty acid synthesis (figure 4.11).', 'a8a38913-a371-48ab-844a-47cc69e6476b': 'In order to maintain a pool of TCA cycle intermediates, as substrates are removed from the cycle, there are\xa0several key reactions (anaplerotic reactions) that\xa0are responsible for the addition of intermediates. These reactions are illustrated in figure 4.12. Notice all of these reactions add carbon back to the cycle from amino acids (reactions 1, 2, 3, 4, 5). These will become very important in the discussion of gluconeogenesis where these substrates will provide the majority of carbon for glucose production. Odd chain fatty acid oxidation can also provide carbon in the from of propionyl-CoA (3) although this is not a primary source of TCA cycle intermediates.', 'bcba9f79-02f4-4bd8-af3b-68761776a585': 'Likewise, α-ketoglutarate dehydrogenase can be activated by Ca2+ and inhibited by NADH (and succinyl-CoA) (figure 4.13).', '0674e92c-bf8b-44e0-93a6-1ff984cea24c': 'Malate dehydrogenase can also be inhibited by NADH, however, the reaction is reversible depending on levels of NADH. The oxidation of malate to OAA requires NAD+, and under certain pathological situations the lack of free NAD+ within the mitochondria will reduce the rate of this reaction (this is common in\xa0the case of alcohol metabolism).', '769e382b-4493-4957-bd34-61228dcc16eb': 'Keep in mind that with the addition of each acetyl-CoA (comprised of 2 carbons) to the TCA cycle, two molecules of CO2 are released, thus there is no net gain or loss of carbons in the cycle. The process moves forward driven by energetics and substrate availability. The pathway can be active in both the fed and fasted states. In the fed state, acetyl-CoA is generated primarily through glucose oxidation. In contrast, in the fasted state acetyl-CoA is generated primarily from β-oxidation, and the majority of acetyl-CoA is used to synthesize ketones.', 'bbe38e2f-4233-4123-ad47-00967f8b2d53': 'Table 4.2: Summary of pathway regulation.', 'a0f3960c-37d6-4a27-8622-1dc59b59df98': '4.2 References and resources', '56280a32-2096-4292-b0e3-d81d7a1b5bdf': 'Lieberman M, Peet A. Figure 4.12 Anaplerotic reactions of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 473. Figure 23.18 Major anaplerotic pathways of the tricarboxylic acid (TCA) cycle. 2017.', '43c2a05d-f08c-4ef1-93e3-cc3a9d4e31be': 'Lieberman M, Peet A. Figure 4.13 Regulation of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 468. Figure 23.11 Major regulatory interaction in the tricarboxylic acid (TCA) cycle. 2017. Added ion channel by Léa Lortal from the Noun Project.', 'a20c5f37-73c1-4597-85fc-15ca116b23fd': '4.3 Electron Transport Chain (ETC)', '27b219b9-971b-4a3e-a1ca-6627180e7ddc': 'In the production of NADH and FADH2 by the TCA cycle, β-oxidation or glycolysis is funneled directly into the electron transport chain (ETC) where each of these reduced coenzymes will donate two electrons to electron carriers. As the electrons are passed down their oxidation gradient, some of the energy is lost, but much of this energy is used to pump protons into the intermembrane space of the mitochondria.', 'b786884b-a1de-4583-93be-18ced847fd32': 'The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).', 'bad771c1-d83d-41ca-8988-296308499c6f': 'There are site specific inhibitors of the ETC to be aware of, and these will disrupt electron flow reducing overall ATP production.'}"
Figure 4.13,cell_bio/images/Figure 4.13.jpg,Figure 4.13: Regulation of the TCA cycle.,"Likewise, α-ketoglutarate dehydrogenase can be activated by Ca2+ and inhibited by NADH (and succinyl-CoA) (figure 4.13).","{'bcba9f79-02f4-4bd8-af3b-68761776a585': 'Likewise, α-ketoglutarate dehydrogenase can be activated by Ca2+ and inhibited by NADH (and succinyl-CoA) (figure 4.13).', '0674e92c-bf8b-44e0-93a6-1ff984cea24c': 'Malate dehydrogenase can also be inhibited by NADH, however, the reaction is reversible depending on levels of NADH. The oxidation of malate to OAA requires NAD+, and under certain pathological situations the lack of free NAD+ within the mitochondria will reduce the rate of this reaction (this is common in\xa0the case of alcohol metabolism).', '769e382b-4493-4957-bd34-61228dcc16eb': 'Keep in mind that with the addition of each acetyl-CoA (comprised of 2 carbons) to the TCA cycle, two molecules of CO2 are released, thus there is no net gain or loss of carbons in the cycle. The process moves forward driven by energetics and substrate availability. The pathway can be active in both the fed and fasted states. In the fed state, acetyl-CoA is generated primarily through glucose oxidation. In contrast, in the fasted state acetyl-CoA is generated primarily from β-oxidation, and the majority of acetyl-CoA is used to synthesize ketones.', 'bbe38e2f-4233-4123-ad47-00967f8b2d53': 'Table 4.2: Summary of pathway regulation.', 'a0f3960c-37d6-4a27-8622-1dc59b59df98': '4.2 References and resources', '56280a32-2096-4292-b0e3-d81d7a1b5bdf': 'Lieberman M, Peet A. Figure 4.12 Anaplerotic reactions of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 473. Figure 23.18 Major anaplerotic pathways of the tricarboxylic acid (TCA) cycle. 2017.', '43c2a05d-f08c-4ef1-93e3-cc3a9d4e31be': 'Lieberman M, Peet A. Figure 4.13 Regulation of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 468. Figure 23.11 Major regulatory interaction in the tricarboxylic acid (TCA) cycle. 2017. Added ion channel by Léa Lortal from the Noun Project.', 'a20c5f37-73c1-4597-85fc-15ca116b23fd': '4.3 Electron Transport Chain (ETC)', '27b219b9-971b-4a3e-a1ca-6627180e7ddc': 'In the production of NADH and FADH2 by the TCA cycle, β-oxidation or glycolysis is funneled directly into the electron transport chain (ETC) where each of these reduced coenzymes will donate two electrons to electron carriers. As the electrons are passed down their oxidation gradient, some of the energy is lost, but much of this energy is used to pump protons into the intermembrane space of the mitochondria.', 'b786884b-a1de-4583-93be-18ced847fd32': 'The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).', 'bad771c1-d83d-41ca-8988-296308499c6f': 'There are site specific inhibitors of the ETC to be aware of, and these will disrupt electron flow reducing overall ATP production.'}"
Figure 4.10,cell_bio/images/Figure 4.10.jpg,Figure 4.10: Overview of the TCA cycle.,"The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).","{'fb88e68b-0221-4412-9b06-56553062ebb5': 'Table 7.1: Summary of pathway regulation.', 'aec2819a-a20f-441e-8bb9-ac1a9c244b9c': '7.1 References and resources', '6b3b2e3a-d57d-416e-9a30-e88c5f4a7b8a': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 13: Pentose Phosphate Pathway and NAPDH, Chapter 22: Nucleotide Metabolism.', '9d5c48f7-a337-45b3-9591-0b2ecb659d51': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 35–37, 79.', '2037d387-961d-463e-9059-7136f0139c90': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 27: Pentose Phosphate Pathway, Chapter 39: Purine and Pyrimidine Synthesis.', '66cea327-3e3b-44c7-9cc6-e1a3d1e25c21': 'Lieberman M, Peet A. Figure 7.1 Overview of the pentose phosphate pathway and its interface with glycolysis. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 543. Figure 27.1 Overview of the pentose phosphate pathway. 2017.', '519c386e-ebb1-48ee-bd20-6515b2fa93d1': 'Lieberman M, Peet A. Figure 7.3 NADPH in the red blood cell as a means of reducing glutathione. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 549. Figure 27.7 Hemolysis caused by reactive oxygen species (ROS). 2017.', '1346248e-2709-4a17-9ba1-a6bccf35cca0': '7.2 Nucleotide Synthesis', '396185b1-1dbc-427b-acb3-35b6417eebff': 'Nucleotides are the fundamental building blocks essential for the synthesis of DNA and RNA. Each nucleotide contains three\xa0functional groups: a sugar, a base, and phosphate (figure 7.4).', '3946bf72-a982-47ba-b4e5-bc6324d8c5f3': 'Nucleotides can be divided into two groups: pyrimidines and purines. The family of pyrimidines includes thymine (T), cytosine (C), and uracil (U), which is only incorporated into RNA. These compounds contain a single-ringed nitrogenous base that pairs with a purine nucleotide counterpart. Thymine pairs with adenine forming two hydrogen bonds, in contrast to cytosine, which pairs with guanine to form three hydrogen bonds. Purines, both guanine (G) and adenine (A), are double-ringed structures and more difficult to break down in the body. As such, the salvage pathway for purine metabolism is of importance (figure 7.5).', 'fc7741dd-78b4-488f-943b-2d86b7c23ddc': 'Nucleotide synthesis will be described below, but one of the fundamental requirements of the synthesis of either purines or pyrimidines is the need for a five-carbon sugar (ribose). This sugar is generated through glucose oxidation via the pentose phosphate pathway.', 'c4d80872-6249-48af-837c-c13415097e87': 'For purines synthesis, the base is synthesized and attached to the sugar, while for pyrimidine synthesis, the sugar group is added after the base is produced. In either case, ribose is the added sugar, and this must be converted to the deoxyribose form before the bases can be used for DNA synthesis.', '6aa6a40f-ccef-4e08-90f9-792fcc96a0b2': 'Table 5.1: Summary of pathway regulation.', '09cc9c78-560d-4da8-b03b-4f4d4dc1efe7': '5.1 References and resources', 'a0533ceb-fbf0-43f2-956c-40dca7e555e8': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 10: Gluconeogenesis: Section II, III, IV, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section III, IV, V, Chapter 19: Removal of Nitrogen from Amino Acids: Section V, VI, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', 'b4146c8c-38a4-42e0-a148-5f101ceaf66f': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 78, 82, 86, 89–90.', '49133e69-5fc3-46ce-a3fe-66c9fd162e74': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 3: The Fasted State, Chapter 19: Basic Concepts in Regulation, Chapter 24: Oxidative Phosphorylation and the ETC, Chapter 26: Formation of Glycogen, Chapter 28: Gluconeogenesis, Chapter 30: Oxidation of Fatty Acids, Chapter 34: Integration of Carbohydrate and Lipid Metabolism, Chapter 36: Fate of Amino Acids Nitrogen: Urea Cycle.', '20d405f0-cd3d-4473-b170-f2e2ae4a0a30': 'Ferrier D. Figure 5.1 Glucose production by glycogenolysis and gluconeogenesis. Adapted under Fair Use from Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp 329. Figure 24.11 Sources of blood glucose after ingestion of 100 g of glucose. 2017.', 'e9cea747-d390-4b49-91d9-1135adf763aa': 'Lieberman M, Peet A. Figure 5.6 Hepatic glycogenolysis by epinephrine. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 534. Figure 26.7 Regulation of glycogen synthesis and degradation in the liver. 2017. Added ion channel by Léa Lortal from the Noun Project.', '4338022d-aaa7-4b00-aea9-503a6ebe50be': '5.2 Lipolysis, β-oxidation, and Ketogenesis', 'b5b6da0b-d292-48ae-adb5-f481024dd9d6': 'The processes of lipolysis, β-oxidation, and ketogenesis work in concert within the cell but should be considered distinct pathways.', '7a500298-e875-471b-8309-393871378e6d': 'Table 4.1: Summary of pathway regulation.', 'dd2c9d30-3292-4bdb-8daf-c318feeb6309': '4.1 References and resources', '3e593a1a-7907-43ee-b913-bb6429005204': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 6: Bioenergetics and Oxidative Phosphorylation: Section V, VI, Chapter 8: Introduction to Metabolism and Glycolysis, Chapter 9: TCA Cycle and Pyruvate Dehydrogenase Complex: Section IIA, IIB, Chapter 11: Glycogen Metabolism: Section V, VI, Chapter 16: Fatty Acid Ketone Body and TAG Metabolism: Section II, IV, V, Chapter 23: Metabolic Effect of Insulin and Glucagon, Chapter 25: Diabetes Mellitus.', '67748f32-55ad-4385-9ecc-749abb04b3e9': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 72–78, 85–89.', '7ff36049-e9fc-4281-9709-d04b9e27ccec': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 19: Basic Concepts of Regulation: Section IV.A.1.2, Chapter 20: Cellular Bioenergetics, Chapter 22: Generation of ATP from Glucose: Section I.A.B.C, III, Chapter 24: Oxidative Phosphorylation and the ETC: Section I.E, II, III, Chapter 31: Synthesis of Fatty Acids: Section I.A.B, IV, V.', '09b30862-fd9e-4711-b247-160213284a3d': 'Lieberman M, Peet A. Figure 4.3 Comparison of glucokinase and hexokinase kinetics. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 154. Figure 9.4 A comparison between hexokinase I and glucokinase. 2017.', 'a9219e02-815e-45a2-9ea0-ac4cf864fbf2': 'Lieberman M, Peet A. Figure 4.9 Regulation of the PDC. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 471. Figure 23.15 Regulation of pyruvate dehydroenase complex (PDC). 2017.', 'fc836e5e-c1c9-4928-a443-aa96409e1819': '4.2 Tricarboxylic Acid Cycle (TCA)', 'b98942e4-1e12-4e85-af17-81675ddeae43': 'The TCA cycle is responsible for generating over half of the ATP from the oxidation of fuels. This is primarily because the substrate for the TCA cycle, acetyl-CoA, is generated by the oxidation of fatty acids, glucose, amino acids, and ketone bodies. With each turn of the TCA cycle, there is a net production of three\xa0NADH, FADH2, two CO2, and one GTP for every acetyl-CoA that enters (figure 4.10).', 'bcba9f79-02f4-4bd8-af3b-68761776a585': 'Likewise, α-ketoglutarate dehydrogenase can be activated by Ca2+ and inhibited by NADH (and succinyl-CoA) (figure 4.13).', '0674e92c-bf8b-44e0-93a6-1ff984cea24c': 'Malate dehydrogenase can also be inhibited by NADH, however, the reaction is reversible depending on levels of NADH. The oxidation of malate to OAA requires NAD+, and under certain pathological situations the lack of free NAD+ within the mitochondria will reduce the rate of this reaction (this is common in\xa0the case of alcohol metabolism).', '769e382b-4493-4957-bd34-61228dcc16eb': 'Keep in mind that with the addition of each acetyl-CoA (comprised of 2 carbons) to the TCA cycle, two molecules of CO2 are released, thus there is no net gain or loss of carbons in the cycle. The process moves forward driven by energetics and substrate availability. The pathway can be active in both the fed and fasted states. In the fed state, acetyl-CoA is generated primarily through glucose oxidation. In contrast, in the fasted state acetyl-CoA is generated primarily from β-oxidation, and the majority of acetyl-CoA is used to synthesize ketones.', 'bbe38e2f-4233-4123-ad47-00967f8b2d53': 'Table 4.2: Summary of pathway regulation.', 'a0f3960c-37d6-4a27-8622-1dc59b59df98': '4.2 References and resources', '56280a32-2096-4292-b0e3-d81d7a1b5bdf': 'Lieberman M, Peet A. Figure 4.12 Anaplerotic reactions of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 473. Figure 23.18 Major anaplerotic pathways of the tricarboxylic acid (TCA) cycle. 2017.', '43c2a05d-f08c-4ef1-93e3-cc3a9d4e31be': 'Lieberman M, Peet A. Figure 4.13 Regulation of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 468. Figure 23.11 Major regulatory interaction in the tricarboxylic acid (TCA) cycle. 2017. Added ion channel by Léa Lortal from the Noun Project.', 'a20c5f37-73c1-4597-85fc-15ca116b23fd': '4.3 Electron Transport Chain (ETC)', '27b219b9-971b-4a3e-a1ca-6627180e7ddc': 'In the production of NADH and FADH2 by the TCA cycle, β-oxidation or glycolysis is funneled directly into the electron transport chain (ETC) where each of these reduced coenzymes will donate two electrons to electron carriers. As the electrons are passed down their oxidation gradient, some of the energy is lost, but much of this energy is used to pump protons into the intermembrane space of the mitochondria.', 'b786884b-a1de-4583-93be-18ced847fd32': 'The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).', 'bad771c1-d83d-41ca-8988-296308499c6f': 'There are site specific inhibitors of the ETC to be aware of, and these will disrupt electron flow reducing overall ATP production.'}"
Figure 4.11,cell_bio/images/Figure 4.11.jpg,Figure 4.11: Substrates produced by the TCA cycle.,"The other major role of the TCA cycle is to provide substrates for other synthetic pathways. Malate is shuttled out of the TCA cycle and used as a substrate for gluconeogenesis and oxaloacetate (OAA) and α-ketoglutarate are used as substrates for amino acid synthesis. Through transamination reactions, these two keto-acids can be converted into aspartate and glutamate, respectively. α-ketoglutarate is also a key substrate for the synthesis of neurotransmitters, and succinyl-CoA is the substrate for heme synthesis. Citrate is also a key compound as it is both an intermediate of the TCA cycle and can be shuttled into the cytosol to provide acetyl-CoA for both cholesterol and fatty acid synthesis (figure 4.11).","{'642ae580-8500-4860-b02c-2cba56add6cc': 'The other major role of the TCA cycle is to provide substrates for other synthetic pathways. Malate is shuttled out of the TCA cycle and used as a substrate for gluconeogenesis and\xa0oxaloacetate (OAA) and α-ketoglutarate are used as substrates for amino acid synthesis. Through transamination reactions, these two keto-acids can be converted into aspartate and glutamate, respectively. α-ketoglutarate is also a key substrate for the synthesis of neurotransmitters, and succinyl-CoA is the substrate for heme synthesis. Citrate is also a key compound as it is both an intermediate of the TCA cycle and can be shuttled into the cytosol to provide acetyl-CoA for both cholesterol and fatty acid synthesis (figure 4.11).', 'a8a38913-a371-48ab-844a-47cc69e6476b': 'In order to maintain a pool of TCA cycle intermediates, as substrates are removed from the cycle, there are\xa0several key reactions (anaplerotic reactions) that\xa0are responsible for the addition of intermediates. These reactions are illustrated in figure 4.12. Notice all of these reactions add carbon back to the cycle from amino acids (reactions 1, 2, 3, 4, 5). These will become very important in the discussion of gluconeogenesis where these substrates will provide the majority of carbon for glucose production. Odd chain fatty acid oxidation can also provide carbon in the from of propionyl-CoA (3) although this is not a primary source of TCA cycle intermediates.', 'bcba9f79-02f4-4bd8-af3b-68761776a585': 'Likewise, α-ketoglutarate dehydrogenase can be activated by Ca2+ and inhibited by NADH (and succinyl-CoA) (figure 4.13).', '0674e92c-bf8b-44e0-93a6-1ff984cea24c': 'Malate dehydrogenase can also be inhibited by NADH, however, the reaction is reversible depending on levels of NADH. The oxidation of malate to OAA requires NAD+, and under certain pathological situations the lack of free NAD+ within the mitochondria will reduce the rate of this reaction (this is common in\xa0the case of alcohol metabolism).', '769e382b-4493-4957-bd34-61228dcc16eb': 'Keep in mind that with the addition of each acetyl-CoA (comprised of 2 carbons) to the TCA cycle, two molecules of CO2 are released, thus there is no net gain or loss of carbons in the cycle. The process moves forward driven by energetics and substrate availability. The pathway can be active in both the fed and fasted states. In the fed state, acetyl-CoA is generated primarily through glucose oxidation. In contrast, in the fasted state acetyl-CoA is generated primarily from β-oxidation, and the majority of acetyl-CoA is used to synthesize ketones.', 'bbe38e2f-4233-4123-ad47-00967f8b2d53': 'Table 4.2: Summary of pathway regulation.', 'a0f3960c-37d6-4a27-8622-1dc59b59df98': '4.2 References and resources', '56280a32-2096-4292-b0e3-d81d7a1b5bdf': 'Lieberman M, Peet A. Figure 4.12 Anaplerotic reactions of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 473. Figure 23.18 Major anaplerotic pathways of the tricarboxylic acid (TCA) cycle. 2017.', '43c2a05d-f08c-4ef1-93e3-cc3a9d4e31be': 'Lieberman M, Peet A. Figure 4.13 Regulation of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 468. Figure 23.11 Major regulatory interaction in the tricarboxylic acid (TCA) cycle. 2017. Added ion channel by Léa Lortal from the Noun Project.', 'a20c5f37-73c1-4597-85fc-15ca116b23fd': '4.3 Electron Transport Chain (ETC)', '27b219b9-971b-4a3e-a1ca-6627180e7ddc': 'In the production of NADH and FADH2 by the TCA cycle, β-oxidation or glycolysis is funneled directly into the electron transport chain (ETC) where each of these reduced coenzymes will donate two electrons to electron carriers. As the electrons are passed down their oxidation gradient, some of the energy is lost, but much of this energy is used to pump protons into the intermembrane space of the mitochondria.', 'b786884b-a1de-4583-93be-18ced847fd32': 'The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).', 'bad771c1-d83d-41ca-8988-296308499c6f': 'There are site specific inhibitors of the ETC to be aware of, and these will disrupt electron flow reducing overall ATP production.'}"
Figure 4.12,cell_bio/images/Figure 4.12.jpg,Figure 4.12: Anaplerotic reactions of the TCA cycle.,"In order to maintain a pool of TCA cycle intermediates, as substrates are removed from the cycle, there are several key reactions (anaplerotic reactions) that are responsible for the addition of intermediates. These reactions are illustrated in figure 4.12. Notice all of these reactions add carbon back to the cycle from amino acids (reactions 1, 2, 3, 4, 5). These will become very important in the discussion of gluconeogenesis where these substrates will provide the majority of carbon for glucose production. Odd chain fatty acid oxidation can also provide carbon in the from of propionyl-CoA (3) although this is not a primary source of TCA cycle intermediates.","{'642ae580-8500-4860-b02c-2cba56add6cc': 'The other major role of the TCA cycle is to provide substrates for other synthetic pathways. Malate is shuttled out of the TCA cycle and used as a substrate for gluconeogenesis and\xa0oxaloacetate (OAA) and α-ketoglutarate are used as substrates for amino acid synthesis. Through transamination reactions, these two keto-acids can be converted into aspartate and glutamate, respectively. α-ketoglutarate is also a key substrate for the synthesis of neurotransmitters, and succinyl-CoA is the substrate for heme synthesis. Citrate is also a key compound as it is both an intermediate of the TCA cycle and can be shuttled into the cytosol to provide acetyl-CoA for both cholesterol and fatty acid synthesis (figure 4.11).', 'a8a38913-a371-48ab-844a-47cc69e6476b': 'In order to maintain a pool of TCA cycle intermediates, as substrates are removed from the cycle, there are\xa0several key reactions (anaplerotic reactions) that\xa0are responsible for the addition of intermediates. These reactions are illustrated in figure 4.12. Notice all of these reactions add carbon back to the cycle from amino acids (reactions 1, 2, 3, 4, 5). These will become very important in the discussion of gluconeogenesis where these substrates will provide the majority of carbon for glucose production. Odd chain fatty acid oxidation can also provide carbon in the from of propionyl-CoA (3) although this is not a primary source of TCA cycle intermediates.', 'bcba9f79-02f4-4bd8-af3b-68761776a585': 'Likewise, α-ketoglutarate dehydrogenase can be activated by Ca2+ and inhibited by NADH (and succinyl-CoA) (figure 4.13).', '0674e92c-bf8b-44e0-93a6-1ff984cea24c': 'Malate dehydrogenase can also be inhibited by NADH, however, the reaction is reversible depending on levels of NADH. The oxidation of malate to OAA requires NAD+, and under certain pathological situations the lack of free NAD+ within the mitochondria will reduce the rate of this reaction (this is common in\xa0the case of alcohol metabolism).', '769e382b-4493-4957-bd34-61228dcc16eb': 'Keep in mind that with the addition of each acetyl-CoA (comprised of 2 carbons) to the TCA cycle, two molecules of CO2 are released, thus there is no net gain or loss of carbons in the cycle. The process moves forward driven by energetics and substrate availability. The pathway can be active in both the fed and fasted states. In the fed state, acetyl-CoA is generated primarily through glucose oxidation. In contrast, in the fasted state acetyl-CoA is generated primarily from β-oxidation, and the majority of acetyl-CoA is used to synthesize ketones.', 'bbe38e2f-4233-4123-ad47-00967f8b2d53': 'Table 4.2: Summary of pathway regulation.', 'a0f3960c-37d6-4a27-8622-1dc59b59df98': '4.2 References and resources', '56280a32-2096-4292-b0e3-d81d7a1b5bdf': 'Lieberman M, Peet A. Figure 4.12 Anaplerotic reactions of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 473. Figure 23.18 Major anaplerotic pathways of the tricarboxylic acid (TCA) cycle. 2017.', '43c2a05d-f08c-4ef1-93e3-cc3a9d4e31be': 'Lieberman M, Peet A. Figure 4.13 Regulation of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 468. Figure 23.11 Major regulatory interaction in the tricarboxylic acid (TCA) cycle. 2017. Added ion channel by Léa Lortal from the Noun Project.', 'a20c5f37-73c1-4597-85fc-15ca116b23fd': '4.3 Electron Transport Chain (ETC)', '27b219b9-971b-4a3e-a1ca-6627180e7ddc': 'In the production of NADH and FADH2 by the TCA cycle, β-oxidation or glycolysis is funneled directly into the electron transport chain (ETC) where each of these reduced coenzymes will donate two electrons to electron carriers. As the electrons are passed down their oxidation gradient, some of the energy is lost, but much of this energy is used to pump protons into the intermembrane space of the mitochondria.', 'b786884b-a1de-4583-93be-18ced847fd32': 'The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).', 'bad771c1-d83d-41ca-8988-296308499c6f': 'There are site specific inhibitors of the ETC to be aware of, and these will disrupt electron flow reducing overall ATP production.'}"
Figure 4.14,cell_bio/images/Figure 4.14.jpg,Figure 4.14: Overview of the electron transport chain (ETC).,"The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).","{'bcba9f79-02f4-4bd8-af3b-68761776a585': 'Likewise, α-ketoglutarate dehydrogenase can be activated by Ca2+ and inhibited by NADH (and succinyl-CoA) (figure 4.13).', '0674e92c-bf8b-44e0-93a6-1ff984cea24c': 'Malate dehydrogenase can also be inhibited by NADH, however, the reaction is reversible depending on levels of NADH. The oxidation of malate to OAA requires NAD+, and under certain pathological situations the lack of free NAD+ within the mitochondria will reduce the rate of this reaction (this is common in\xa0the case of alcohol metabolism).', '769e382b-4493-4957-bd34-61228dcc16eb': 'Keep in mind that with the addition of each acetyl-CoA (comprised of 2 carbons) to the TCA cycle, two molecules of CO2 are released, thus there is no net gain or loss of carbons in the cycle. The process moves forward driven by energetics and substrate availability. The pathway can be active in both the fed and fasted states. In the fed state, acetyl-CoA is generated primarily through glucose oxidation. In contrast, in the fasted state acetyl-CoA is generated primarily from β-oxidation, and the majority of acetyl-CoA is used to synthesize ketones.', 'bbe38e2f-4233-4123-ad47-00967f8b2d53': 'Table 4.2: Summary of pathway regulation.', 'a0f3960c-37d6-4a27-8622-1dc59b59df98': '4.2 References and resources', '56280a32-2096-4292-b0e3-d81d7a1b5bdf': 'Lieberman M, Peet A. Figure 4.12 Anaplerotic reactions of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 473. Figure 23.18 Major anaplerotic pathways of the tricarboxylic acid (TCA) cycle. 2017.', '43c2a05d-f08c-4ef1-93e3-cc3a9d4e31be': 'Lieberman M, Peet A. Figure 4.13 Regulation of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 468. Figure 23.11 Major regulatory interaction in the tricarboxylic acid (TCA) cycle. 2017. Added ion channel by Léa Lortal from the Noun Project.', 'a20c5f37-73c1-4597-85fc-15ca116b23fd': '4.3 Electron Transport Chain (ETC)', '27b219b9-971b-4a3e-a1ca-6627180e7ddc': 'In the production of NADH and FADH2 by the TCA cycle, β-oxidation or glycolysis is funneled directly into the electron transport chain (ETC) where each of these reduced coenzymes will donate two electrons to electron carriers. As the electrons are passed down their oxidation gradient, some of the energy is lost, but much of this energy is used to pump protons into the intermembrane space of the mitochondria.', 'b786884b-a1de-4583-93be-18ced847fd32': 'The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).', 'bad771c1-d83d-41ca-8988-296308499c6f': 'There are site specific inhibitors of the ETC to be aware of, and these will disrupt electron flow reducing overall ATP production.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 4.14,cell_bio/images/Figure 4.14.jpg,Figure 4.14: Overview of the electron transport chain (ETC).,"The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).","{'bcba9f79-02f4-4bd8-af3b-68761776a585': 'Likewise, α-ketoglutarate dehydrogenase can be activated by Ca2+ and inhibited by NADH (and succinyl-CoA) (figure 4.13).', '0674e92c-bf8b-44e0-93a6-1ff984cea24c': 'Malate dehydrogenase can also be inhibited by NADH, however, the reaction is reversible depending on levels of NADH. The oxidation of malate to OAA requires NAD+, and under certain pathological situations the lack of free NAD+ within the mitochondria will reduce the rate of this reaction (this is common in\xa0the case of alcohol metabolism).', '769e382b-4493-4957-bd34-61228dcc16eb': 'Keep in mind that with the addition of each acetyl-CoA (comprised of 2 carbons) to the TCA cycle, two molecules of CO2 are released, thus there is no net gain or loss of carbons in the cycle. The process moves forward driven by energetics and substrate availability. The pathway can be active in both the fed and fasted states. In the fed state, acetyl-CoA is generated primarily through glucose oxidation. In contrast, in the fasted state acetyl-CoA is generated primarily from β-oxidation, and the majority of acetyl-CoA is used to synthesize ketones.', 'bbe38e2f-4233-4123-ad47-00967f8b2d53': 'Table 4.2: Summary of pathway regulation.', 'a0f3960c-37d6-4a27-8622-1dc59b59df98': '4.2 References and resources', '56280a32-2096-4292-b0e3-d81d7a1b5bdf': 'Lieberman M, Peet A. Figure 4.12 Anaplerotic reactions of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 473. Figure 23.18 Major anaplerotic pathways of the tricarboxylic acid (TCA) cycle. 2017.', '43c2a05d-f08c-4ef1-93e3-cc3a9d4e31be': 'Lieberman M, Peet A. Figure 4.13 Regulation of the TCA cycle. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 468. Figure 23.11 Major regulatory interaction in the tricarboxylic acid (TCA) cycle. 2017. Added ion channel by Léa Lortal from the Noun Project.', 'a20c5f37-73c1-4597-85fc-15ca116b23fd': '4.3 Electron Transport Chain (ETC)', '27b219b9-971b-4a3e-a1ca-6627180e7ddc': 'In the production of NADH and FADH2 by the TCA cycle, β-oxidation or glycolysis is funneled directly into the electron transport chain (ETC) where each of these reduced coenzymes will donate two electrons to electron carriers. As the electrons are passed down their oxidation gradient, some of the energy is lost, but much of this energy is used to pump protons into the intermembrane space of the mitochondria.', 'b786884b-a1de-4583-93be-18ced847fd32': 'The process of oxidative phosphorylation (figure 4.14) involves the coupling of electron transfer with the pumping of protons to generate an electrochemical gradient across the mitochondrial membrane. With the exception of CoQ all proteins are bound to the mitochondria membrane, and electrons are passed between metal containing cytochromes. Complex I and Complex II function in parallel (rather than series) with each other having preference for NADH or FADH2, respectively. Complex II (succinate dehydrogenase) is not required for oxidative phosphorylation because it does not span the mitochondrial membrane (figure 4.14). Electrons are passed down an electrochemical gradient, and molecular oxygen is the final electron acceptor (molecular oxygen).', 'bad771c1-d83d-41ca-8988-296308499c6f': 'There are site specific inhibitors of the ETC to be aware of, and these will disrupt electron flow reducing overall ATP production.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 4.15,cell_bio/images/Figure 4.15.jpg,Figure 4.15: Citrate shuttle reaction moves citrate from the mitochondria to the cytosol for fatty acid synthesis.,"The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).","{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.', '475f728a-5cc6-4dc1-8c11-7bc1c6a508ce': 'Acetyl-CoA carboxylase is the regulatory enzyme for fatty acid synthesis. This enzyme is regulated both allosterically and through covalent modification. It is allosterically activated by high levels of citrate and inhibited by its product, fatty acyl-CoA. It can also be inhibited by elevated levels of glucagon, epinephrine, and adenosine monophosphate (AMP)-activated protein kinase phosphorylation. Insulin will stimulate the dephosphorylation and activation of the enzyme such that it can be active in the fed state (figure 4.17).', 'c01831fa-ed9e-4513-b4a8-9a722bcad21f': 'Table 4.3: Summary of pathway regulation.', '45f5e214-90b1-4aaf-a8a3-a0ae12dd179f': '4.4 References and resources', '45aaf6e1-61af-4aab-9312-0d2ac795dd67': '4.5 Glycogen Synthesis', '092db27a-30bf-416f-b895-ee990b13547b': 'Glycogen synthesis is the process of storing glucose and occurs primarily in the liver and the skeletal muscle. The metabolic pathways in these tissues are similar, but the utility of glycogen stores is different. Briefly, liver glycogen is catabolized primarily in response to elevated glucagon, and the glucose 6-phosphate generated is dephosphorylated and released into circulation. In contrast, muscle glycogen is only used by the muscle itself; muscle lacks glucose 6-phosphatase and glucose 6-phosphate released from muscle glycogen is oxidized in glycolysis. Although discussed here as a point of comparison, glycogenolysis is a fasted state pathway and occurs in response to glucagon and epinephrine. This will be discussed in section 5.1.', 'a70e1786-d06e-4ae9-80eb-db54ff99e86e': 'Initially glucose 6-phosphate, is isomerized to glucose 1-phosphate. UDP-glucose pyrophosphorylase synthesizes UDP-glucose from glucose 1-phosphate and UTP, and this is the source of all the glycosyl residues added to the growing glycogen chain (figure 4.18). Glycogen synthase is the regulatory enzyme for the pathway and is responsible for linking glycosyl residues in a 1,4 linkage. The reaction typically occurs on existing glycogen stores; however, in the absence of any stored glycogen the reaction can occur on the protein primer, glycogenin.'}"
Figure 4.16,cell_bio/images/Figure 4.16.jpg,"Figure 4.16: Fatty acid synthesis is an iterative process that begins with the transfer of an acetyl moiety from acetyl-CoA to fatty acid synthase; following this activation, carbons are added to the growing chain in the form of malonyl-CoA.","The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).","{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.', '475f728a-5cc6-4dc1-8c11-7bc1c6a508ce': 'Acetyl-CoA carboxylase is the regulatory enzyme for fatty acid synthesis. This enzyme is regulated both allosterically and through covalent modification. It is allosterically activated by high levels of citrate and inhibited by its product, fatty acyl-CoA. It can also be inhibited by elevated levels of glucagon, epinephrine, and adenosine monophosphate (AMP)-activated protein kinase phosphorylation. Insulin will stimulate the dephosphorylation and activation of the enzyme such that it can be active in the fed state (figure 4.17).', 'c01831fa-ed9e-4513-b4a8-9a722bcad21f': 'Table 4.3: Summary of pathway regulation.', '45f5e214-90b1-4aaf-a8a3-a0ae12dd179f': '4.4 References and resources', '45aaf6e1-61af-4aab-9312-0d2ac795dd67': '4.5 Glycogen Synthesis', '092db27a-30bf-416f-b895-ee990b13547b': 'Glycogen synthesis is the process of storing glucose and occurs primarily in the liver and the skeletal muscle. The metabolic pathways in these tissues are similar, but the utility of glycogen stores is different. Briefly, liver glycogen is catabolized primarily in response to elevated glucagon, and the glucose 6-phosphate generated is dephosphorylated and released into circulation. In contrast, muscle glycogen is only used by the muscle itself; muscle lacks glucose 6-phosphatase and glucose 6-phosphate released from muscle glycogen is oxidized in glycolysis. Although discussed here as a point of comparison, glycogenolysis is a fasted state pathway and occurs in response to glucagon and epinephrine. This will be discussed in section 5.1.', 'a70e1786-d06e-4ae9-80eb-db54ff99e86e': 'Initially glucose 6-phosphate, is isomerized to glucose 1-phosphate. UDP-glucose pyrophosphorylase synthesizes UDP-glucose from glucose 1-phosphate and UTP, and this is the source of all the glycosyl residues added to the growing glycogen chain (figure 4.18). Glycogen synthase is the regulatory enzyme for the pathway and is responsible for linking glycosyl residues in a 1,4 linkage. The reaction typically occurs on existing glycogen stores; however, in the absence of any stored glycogen the reaction can occur on the protein primer, glycogenin.'}"
Figure 4.17,cell_bio/images/Figure 4.17.jpg,Figure 4.17: Regulatory reaction of fatty acid synthesis. The synthesis of malonyl-CoA by acetyl-CoA carboxylase is highly regulated within the cytosol.,"Acetyl-CoA carboxylase is the regulatory enzyme for fatty acid synthesis. This enzyme is regulated both allosterically and through covalent modification. It is allosterically activated by high levels of citrate and inhibited by its product, fatty acyl-CoA. It can also be inhibited by elevated levels of glucagon, epinephrine, and adenosine monophosphate (AMP)-activated protein kinase phosphorylation. Insulin will stimulate the dephosphorylation and activation of the enzyme such that it can be active in the fed state (figure 4.17).","{'475f728a-5cc6-4dc1-8c11-7bc1c6a508ce': 'Acetyl-CoA carboxylase is the regulatory enzyme for fatty acid synthesis. This enzyme is regulated both allosterically and through covalent modification. It is allosterically activated by high levels of citrate and inhibited by its product, fatty acyl-CoA. It can also be inhibited by elevated levels of glucagon, epinephrine, and adenosine monophosphate (AMP)-activated protein kinase phosphorylation. Insulin will stimulate the dephosphorylation and activation of the enzyme such that it can be active in the fed state (figure 4.17).', 'c01831fa-ed9e-4513-b4a8-9a722bcad21f': 'Table 4.3: Summary of pathway regulation.', '45f5e214-90b1-4aaf-a8a3-a0ae12dd179f': '4.4 References and resources', '45aaf6e1-61af-4aab-9312-0d2ac795dd67': '4.5 Glycogen Synthesis', '092db27a-30bf-416f-b895-ee990b13547b': 'Glycogen synthesis is the process of storing glucose and occurs primarily in the liver and the skeletal muscle. The metabolic pathways in these tissues are similar, but the utility of glycogen stores is different. Briefly, liver glycogen is catabolized primarily in response to elevated glucagon, and the glucose 6-phosphate generated is dephosphorylated and released into circulation. In contrast, muscle glycogen is only used by the muscle itself; muscle lacks glucose 6-phosphatase and glucose 6-phosphate released from muscle glycogen is oxidized in glycolysis. Although discussed here as a point of comparison, glycogenolysis is a fasted state pathway and occurs in response to glucagon and epinephrine. This will be discussed in section 5.1.', 'a70e1786-d06e-4ae9-80eb-db54ff99e86e': 'Initially glucose 6-phosphate, is isomerized to glucose 1-phosphate. UDP-glucose pyrophosphorylase synthesizes UDP-glucose from glucose 1-phosphate and UTP, and this is the source of all the glycosyl residues added to the growing glycogen chain (figure 4.18). Glycogen synthase is the regulatory enzyme for the pathway and is responsible for linking glycosyl residues in a 1,4 linkage. The reaction typically occurs on existing glycogen stores; however, in the absence of any stored glycogen the reaction can occur on the protein primer, glycogenin.'}"
Figure 4.15,cell_bio/images/Figure 4.15.jpg,Figure 4.15: Citrate shuttle reaction moves citrate from the mitochondria to the cytosol for fatty acid synthesis.,"The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).","{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.', '475f728a-5cc6-4dc1-8c11-7bc1c6a508ce': 'Acetyl-CoA carboxylase is the regulatory enzyme for fatty acid synthesis. This enzyme is regulated both allosterically and through covalent modification. It is allosterically activated by high levels of citrate and inhibited by its product, fatty acyl-CoA. It can also be inhibited by elevated levels of glucagon, epinephrine, and adenosine monophosphate (AMP)-activated protein kinase phosphorylation. Insulin will stimulate the dephosphorylation and activation of the enzyme such that it can be active in the fed state (figure 4.17).', 'c01831fa-ed9e-4513-b4a8-9a722bcad21f': 'Table 4.3: Summary of pathway regulation.', '45f5e214-90b1-4aaf-a8a3-a0ae12dd179f': '4.4 References and resources', '45aaf6e1-61af-4aab-9312-0d2ac795dd67': '4.5 Glycogen Synthesis', '092db27a-30bf-416f-b895-ee990b13547b': 'Glycogen synthesis is the process of storing glucose and occurs primarily in the liver and the skeletal muscle. The metabolic pathways in these tissues are similar, but the utility of glycogen stores is different. Briefly, liver glycogen is catabolized primarily in response to elevated glucagon, and the glucose 6-phosphate generated is dephosphorylated and released into circulation. In contrast, muscle glycogen is only used by the muscle itself; muscle lacks glucose 6-phosphatase and glucose 6-phosphate released from muscle glycogen is oxidized in glycolysis. Although discussed here as a point of comparison, glycogenolysis is a fasted state pathway and occurs in response to glucagon and epinephrine. This will be discussed in section 5.1.', 'a70e1786-d06e-4ae9-80eb-db54ff99e86e': 'Initially glucose 6-phosphate, is isomerized to glucose 1-phosphate. UDP-glucose pyrophosphorylase synthesizes UDP-glucose from glucose 1-phosphate and UTP, and this is the source of all the glycosyl residues added to the growing glycogen chain (figure 4.18). Glycogen synthase is the regulatory enzyme for the pathway and is responsible for linking glycosyl residues in a 1,4 linkage. The reaction typically occurs on existing glycogen stores; however, in the absence of any stored glycogen the reaction can occur on the protein primer, glycogenin.'}"
Figure 4.16,cell_bio/images/Figure 4.16.jpg,"Figure 4.16: Fatty acid synthesis is an iterative process that begins with the transfer of an acetyl moiety from acetyl-CoA to fatty acid synthase; following this activation, carbons are added to the growing chain in the form of malonyl-CoA.","The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).","{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.', '475f728a-5cc6-4dc1-8c11-7bc1c6a508ce': 'Acetyl-CoA carboxylase is the regulatory enzyme for fatty acid synthesis. This enzyme is regulated both allosterically and through covalent modification. It is allosterically activated by high levels of citrate and inhibited by its product, fatty acyl-CoA. It can also be inhibited by elevated levels of glucagon, epinephrine, and adenosine monophosphate (AMP)-activated protein kinase phosphorylation. Insulin will stimulate the dephosphorylation and activation of the enzyme such that it can be active in the fed state (figure 4.17).', 'c01831fa-ed9e-4513-b4a8-9a722bcad21f': 'Table 4.3: Summary of pathway regulation.', '45f5e214-90b1-4aaf-a8a3-a0ae12dd179f': '4.4 References and resources', '45aaf6e1-61af-4aab-9312-0d2ac795dd67': '4.5 Glycogen Synthesis', '092db27a-30bf-416f-b895-ee990b13547b': 'Glycogen synthesis is the process of storing glucose and occurs primarily in the liver and the skeletal muscle. The metabolic pathways in these tissues are similar, but the utility of glycogen stores is different. Briefly, liver glycogen is catabolized primarily in response to elevated glucagon, and the glucose 6-phosphate generated is dephosphorylated and released into circulation. In contrast, muscle glycogen is only used by the muscle itself; muscle lacks glucose 6-phosphatase and glucose 6-phosphate released from muscle glycogen is oxidized in glycolysis. Although discussed here as a point of comparison, glycogenolysis is a fasted state pathway and occurs in response to glucagon and epinephrine. This will be discussed in section 5.1.', 'a70e1786-d06e-4ae9-80eb-db54ff99e86e': 'Initially glucose 6-phosphate, is isomerized to glucose 1-phosphate. UDP-glucose pyrophosphorylase synthesizes UDP-glucose from glucose 1-phosphate and UTP, and this is the source of all the glycosyl residues added to the growing glycogen chain (figure 4.18). Glycogen synthase is the regulatory enzyme for the pathway and is responsible for linking glycosyl residues in a 1,4 linkage. The reaction typically occurs on existing glycogen stores; however, in the absence of any stored glycogen the reaction can occur on the protein primer, glycogenin.'}"
Figure 4.18,cell_bio/images/Figure 4.18.jpg,Figure 4.18: Glycogen synthesis.,"Initially glucose 6-phosphate, is isomerized to glucose 1-phosphate. UDP-glucose pyrophosphorylase synthesizes UDP-glucose from glucose 1-phosphate and UTP, and this is the source of all the glycosyl residues added to the growing glycogen chain (figure 4.18). Glycogen synthase is the regulatory enzyme for the pathway and is responsible for linking glycosyl residues in a 1,4 linkage. The reaction typically occurs on existing glycogen stores; however, in the absence of any stored glycogen the reaction can occur on the protein primer, glycogenin.","{'475f728a-5cc6-4dc1-8c11-7bc1c6a508ce': 'Acetyl-CoA carboxylase is the regulatory enzyme for fatty acid synthesis. This enzyme is regulated both allosterically and through covalent modification. It is allosterically activated by high levels of citrate and inhibited by its product, fatty acyl-CoA. It can also be inhibited by elevated levels of glucagon, epinephrine, and adenosine monophosphate (AMP)-activated protein kinase phosphorylation. Insulin will stimulate the dephosphorylation and activation of the enzyme such that it can be active in the fed state (figure 4.17).', 'c01831fa-ed9e-4513-b4a8-9a722bcad21f': 'Table 4.3: Summary of pathway regulation.', '45f5e214-90b1-4aaf-a8a3-a0ae12dd179f': '4.4 References and resources', '45aaf6e1-61af-4aab-9312-0d2ac795dd67': '4.5 Glycogen Synthesis', '092db27a-30bf-416f-b895-ee990b13547b': 'Glycogen synthesis is the process of storing glucose and occurs primarily in the liver and the skeletal muscle. The metabolic pathways in these tissues are similar, but the utility of glycogen stores is different. Briefly, liver glycogen is catabolized primarily in response to elevated glucagon, and the glucose 6-phosphate generated is dephosphorylated and released into circulation. In contrast, muscle glycogen is only used by the muscle itself; muscle lacks glucose 6-phosphatase and glucose 6-phosphate released from muscle glycogen is oxidized in glycolysis. Although discussed here as a point of comparison, glycogenolysis is a fasted state pathway and occurs in response to glucagon and epinephrine. This will be discussed in section 5.1.', 'a70e1786-d06e-4ae9-80eb-db54ff99e86e': 'Initially glucose 6-phosphate, is isomerized to glucose 1-phosphate. UDP-glucose pyrophosphorylase synthesizes UDP-glucose from glucose 1-phosphate and UTP, and this is the source of all the glycosyl residues added to the growing glycogen chain (figure 4.18). Glycogen synthase is the regulatory enzyme for the pathway and is responsible for linking glycosyl residues in a 1,4 linkage. The reaction typically occurs on existing glycogen stores; however, in the absence of any stored glycogen the reaction can occur on the protein primer, glycogenin.', 'cb68d20a-e08b-42e6-842e-364579ecc854': 'Glycogen synthesis is regulated by a single enzyme, glycogen synthase. This enzyme is primarily regulated through covalent modification. It is active when dephosphorylated and inactive when\xa0phosphorylated. The phosphorylation/dephosphorylation is facilitated by glucagon and insulin levels, respectively (table 4.4).', '137699bf-c8bb-432b-80d5-1c4d12d249d8': 'Table 4.4: Summary of pathway regulation.', '7d8b61fb-56f9-4b27-a4aa-14a584070e8e': '4.5 References and resources', 'bc891e5d-544c-4ae2-8bc4-11035afc9b7b': 'The ratios of these hormones in circulation will dictate the activity of specific metabolic pathways that control glucose homeostasis in a range of 80 mg/dL to 120 mg/dL. There are many other hormones (thyroid hormone, growth hormone, etc.) and adipokines (adiponectin, leptin, etc.) that can influence glucose homeostasis, as well as\xa0neural mechanisms that control higher level functions such as hunger and satiety. These will not be the focus of this section.'}"
Figure 4.18,cell_bio/images/Figure 4.18.jpg,Figure 4.18: Glycogen synthesis.,"Initially glucose 6-phosphate, is isomerized to glucose 1-phosphate. UDP-glucose pyrophosphorylase synthesizes UDP-glucose from glucose 1-phosphate and UTP, and this is the source of all the glycosyl residues added to the growing glycogen chain (figure 4.18). Glycogen synthase is the regulatory enzyme for the pathway and is responsible for linking glycosyl residues in a 1,4 linkage. The reaction typically occurs on existing glycogen stores; however, in the absence of any stored glycogen the reaction can occur on the protein primer, glycogenin.","{'475f728a-5cc6-4dc1-8c11-7bc1c6a508ce': 'Acetyl-CoA carboxylase is the regulatory enzyme for fatty acid synthesis. This enzyme is regulated both allosterically and through covalent modification. It is allosterically activated by high levels of citrate and inhibited by its product, fatty acyl-CoA. It can also be inhibited by elevated levels of glucagon, epinephrine, and adenosine monophosphate (AMP)-activated protein kinase phosphorylation. Insulin will stimulate the dephosphorylation and activation of the enzyme such that it can be active in the fed state (figure 4.17).', 'c01831fa-ed9e-4513-b4a8-9a722bcad21f': 'Table 4.3: Summary of pathway regulation.', '45f5e214-90b1-4aaf-a8a3-a0ae12dd179f': '4.4 References and resources', '45aaf6e1-61af-4aab-9312-0d2ac795dd67': '4.5 Glycogen Synthesis', '092db27a-30bf-416f-b895-ee990b13547b': 'Glycogen synthesis is the process of storing glucose and occurs primarily in the liver and the skeletal muscle. The metabolic pathways in these tissues are similar, but the utility of glycogen stores is different. Briefly, liver glycogen is catabolized primarily in response to elevated glucagon, and the glucose 6-phosphate generated is dephosphorylated and released into circulation. In contrast, muscle glycogen is only used by the muscle itself; muscle lacks glucose 6-phosphatase and glucose 6-phosphate released from muscle glycogen is oxidized in glycolysis. Although discussed here as a point of comparison, glycogenolysis is a fasted state pathway and occurs in response to glucagon and epinephrine. This will be discussed in section 5.1.', 'a70e1786-d06e-4ae9-80eb-db54ff99e86e': 'Initially glucose 6-phosphate, is isomerized to glucose 1-phosphate. UDP-glucose pyrophosphorylase synthesizes UDP-glucose from glucose 1-phosphate and UTP, and this is the source of all the glycosyl residues added to the growing glycogen chain (figure 4.18). Glycogen synthase is the regulatory enzyme for the pathway and is responsible for linking glycosyl residues in a 1,4 linkage. The reaction typically occurs on existing glycogen stores; however, in the absence of any stored glycogen the reaction can occur on the protein primer, glycogenin.', 'cb68d20a-e08b-42e6-842e-364579ecc854': 'Glycogen synthesis is regulated by a single enzyme, glycogen synthase. This enzyme is primarily regulated through covalent modification. It is active when dephosphorylated and inactive when\xa0phosphorylated. The phosphorylation/dephosphorylation is facilitated by glucagon and insulin levels, respectively (table 4.4).', '137699bf-c8bb-432b-80d5-1c4d12d249d8': 'Table 4.4: Summary of pathway regulation.', '7d8b61fb-56f9-4b27-a4aa-14a584070e8e': '4.5 References and resources', 'bc891e5d-544c-4ae2-8bc4-11035afc9b7b': 'The ratios of these hormones in circulation will dictate the activity of specific metabolic pathways that control glucose homeostasis in a range of 80 mg/dL to 120 mg/dL. There are many other hormones (thyroid hormone, growth hormone, etc.) and adipokines (adiponectin, leptin, etc.) that can influence glucose homeostasis, as well as\xa0neural mechanisms that control higher level functions such as hunger and satiety. These will not be the focus of this section.'}"
Figure 3.1,cell_bio/images/Figure 3.1.jpg,Figure 3.1: Overview of the fed state.,"Under these conditions, most tissues (liver, skeletal muscle, adipose, brain, and red blood cells) will increase glucose uptake and oxidation (table 3.1 and figure 3.1).","{'b6d2cfa0-de95-4c60-ac0f-7faaf4605c00': 'In the fed state, or postprandial, elevated glucose levels trigger the release of insulin from the pancreas. As insulin levels rise, there is an increase in glucose uptake, oxidation, and storage in peripheral tissues as well as increases in other anabolic pathways.', 'b30fe9bd-725d-4d25-9e4a-1607efcc11bb': 'Under these conditions, most tissues (liver, skeletal muscle, adipose, brain, and red blood cells) will increase glucose uptake and oxidation (table 3.1 and figure 3.1).', '5291e1f8-19cf-4b9e-a7e3-ae3a3b9a0b12': 'Each tissue will take up glucose in the fed state using one of the glucose transporters (GLUT) known to facilitate glucose transport across the plasma membrane. This family of proteins can be broadly categorized as insulin-independent and insulin-dependent transporters.', 'cf50ecaa-17fd-479a-8744-0cfbce1e3920': 'Table 3.1: Summary table of fuels used in the fed state and uptake methods for important tissues.', '130ada33-1bbd-4224-96c0-120eefb0d066': 'In the liver, glucose is taken up in an insulin-independent manner, and the activity of the following processes increased in the fed state are summarized in figure 3.1 and tables 3.1 and 3.2.', 'c2bbdb21-b5e1-4528-a6a9-a1bad9ad1f07': 'Lieberman, M., A. and Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 3: The Fasted State.', '965ffb94-bc92-413a-afc2-1300b985d8f5': 'Arm muscles anatomical. Public domain. From wpclipart.', 'bc7274da-04ec-46ec-aa32-da7e47ca1335': 'Häggström M, Liver (transparent). Public domain. From Wikimedia Commons.', '0d3fb0a9-624e-4f35-bf53-b9ef91a26fa3': 'LadyofHats, Osmotic pressure on blood cells diagram. Public domain. From Wikimedia Commons.', '09319bf1-e82b-4d7b-8f69-9c09b9a9ab70': 'As a clinician, your first indication of changes to these cellular components will be illustrated by the signs and symptoms of your patient. Following this generalized assessment, you will begin to dissect out a clinical diagnosis by interpreting basic lab values. Each of these elements are indicative of molecular changes ultimately leading to the presentation you are challenged with.', 'b825122b-ef67-44f8-8e43-40a5e90d9718': 'How to read a CMP both clinically and biochemically will help hone the skills of diagnosis and maintenance of health status in patients. Additional laboratory tests such as a lipid profile, blood lactate, or urinalysis may also be ordered to supplement information from the CMP.', '95e43085-48dc-43bf-a6ab-0f3aeeccbabb': 'Deviations in any of these values can help determine changes in substrate availability, cofactors, and\xa0vitamin\xa0or enzymatic deficiencies. It will also help you better understand how biochemical pathways can influence clinical signs and symptoms.'}"
Figure 3.1,cell_bio/images/Figure 3.1.jpg,Figure 3.1: Overview of the fed state.,"Under these conditions, most tissues (liver, skeletal muscle, adipose, brain, and red blood cells) will increase glucose uptake and oxidation (table 3.1 and figure 3.1).","{'b6d2cfa0-de95-4c60-ac0f-7faaf4605c00': 'In the fed state, or postprandial, elevated glucose levels trigger the release of insulin from the pancreas. As insulin levels rise, there is an increase in glucose uptake, oxidation, and storage in peripheral tissues as well as increases in other anabolic pathways.', 'b30fe9bd-725d-4d25-9e4a-1607efcc11bb': 'Under these conditions, most tissues (liver, skeletal muscle, adipose, brain, and red blood cells) will increase glucose uptake and oxidation (table 3.1 and figure 3.1).', '5291e1f8-19cf-4b9e-a7e3-ae3a3b9a0b12': 'Each tissue will take up glucose in the fed state using one of the glucose transporters (GLUT) known to facilitate glucose transport across the plasma membrane. This family of proteins can be broadly categorized as insulin-independent and insulin-dependent transporters.', 'cf50ecaa-17fd-479a-8744-0cfbce1e3920': 'Table 3.1: Summary table of fuels used in the fed state and uptake methods for important tissues.', '130ada33-1bbd-4224-96c0-120eefb0d066': 'In the liver, glucose is taken up in an insulin-independent manner, and the activity of the following processes increased in the fed state are summarized in figure 3.1 and tables 3.1 and 3.2.', 'c2bbdb21-b5e1-4528-a6a9-a1bad9ad1f07': 'Lieberman, M., A. and Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 3: The Fasted State.', '965ffb94-bc92-413a-afc2-1300b985d8f5': 'Arm muscles anatomical. Public domain. From wpclipart.', 'bc7274da-04ec-46ec-aa32-da7e47ca1335': 'Häggström M, Liver (transparent). Public domain. From Wikimedia Commons.', '0d3fb0a9-624e-4f35-bf53-b9ef91a26fa3': 'LadyofHats, Osmotic pressure on blood cells diagram. Public domain. From Wikimedia Commons.', '09319bf1-e82b-4d7b-8f69-9c09b9a9ab70': 'As a clinician, your first indication of changes to these cellular components will be illustrated by the signs and symptoms of your patient. Following this generalized assessment, you will begin to dissect out a clinical diagnosis by interpreting basic lab values. Each of these elements are indicative of molecular changes ultimately leading to the presentation you are challenged with.', 'b825122b-ef67-44f8-8e43-40a5e90d9718': 'How to read a CMP both clinically and biochemically will help hone the skills of diagnosis and maintenance of health status in patients. Additional laboratory tests such as a lipid profile, blood lactate, or urinalysis may also be ordered to supplement information from the CMP.', '95e43085-48dc-43bf-a6ab-0f3aeeccbabb': 'Deviations in any of these values can help determine changes in substrate availability, cofactors, and\xa0vitamin\xa0or enzymatic deficiencies. It will also help you better understand how biochemical pathways can influence clinical signs and symptoms.'}"
Figure 3.2,cell_bio/images/Figure 3.2.jpg,Figure 3.2: Overview of fasted state metabolism.,"The primary role of the liver in the fasted state is to synthesize and release glucose. To facilitate this task, the liver will use circulating free fatty acids as the primary fuel source to generate energy (ATP) for these homeostatic processes. (These processes are summarized in figure 3.2 and tables 3.3 and 3.4)","{'7a3ec35d-40b2-4690-9234-1ee40ac510d9': 'Approximately two\xa0hours after a meal, the decrease in serum glucose levels will lead to decreased insulin production in the pancreas. At this point in fasted state metabolism, the insulin to glucagon ratio becomes\xa0 less than 1 (insulin low; glucagon high) with an additional increase of cortisol and epinephrine. Under these conditions tissues will transition to utilizing alternative fuels for energy as a means of maintaining glucose homeostasis. Fasted state metabolism will have limited impact on the oxidation of glucose by the brain and red blood cells, but it will lead to an increase in fatty acid oxidation by both the skeletal muscle and the liver (figure 3.6). The fatty acids oxidized by these tissues are released through the process of epinephrine-mediated lipolysis from the adipose. In the fasted state, the liver will primarily release glucose using both gluconeogenesis and glycogenolysis for the maintenance of blood glucose.', '301f19d4-f160-4e83-9ec8-21cb3ddbeddf': 'Table 3.3: Summary table of fuels used in the fasted state and the pathways providing the fuel source.', 'd919abd4-f28c-4e7d-b184-33b754662fdd': 'The primary role of the liver in the fasted state is to synthesize and release glucose. To facilitate this task, the liver\xa0will use circulating free fatty acids as the primary fuel source to generate energy (ATP) for these homeostatic processes. (These processes are summarized in figure 3.2 and tables 3.3 and 3.4)', '3b9f1182-e156-4062-8117-dfb0515afdb0': 'The red blood cell lacks mitochondria, therefore it oxidizes glucose under both fed and fasted conditions. The metabolism of this tissue remains largely unchanged.', '51c87026-5818-40cb-8807-fa467ae336a6': 'The brain will oxidize glucose under most conditions with the exception of starvation states. Under normal fasting conditions, although ketones will be synthesized, the brain will not transition to utilizing them as a predominant source of fuel until extended fasting has occurred (days).', 'ff9e2a78-f6bc-4d5f-9a95-1119a4863e17': 'The skeletal muscle will increase uptake of fatty acids and ketones.', 'db1d6849-6e4a-4ee1-929a-184801a22236': 'The most important process in the adipose tissue during the fasted state is lipolysis.', 'c23f64eb-49f7-42d1-bbe7-77d0485d3a7f': 'Table 3.4: Summary of metabolism during the fasted state.', '874810fd-adc1-498c-8a3a-347765c6e50e': '3.1 References and resources', 'fc45a092-3e09-4c54-8fb6-958af0bd3fd7': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 24: Fed Fast Cycle.', '6d7664aa-702b-428d-aaad-63c5b00529a8': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 91, 324–325', 'c2bbdb21-b5e1-4528-a6a9-a1bad9ad1f07': 'Lieberman, M., A. and Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 3: The Fasted State.', '965ffb94-bc92-413a-afc2-1300b985d8f5': 'Arm muscles anatomical. Public domain. From wpclipart.', 'bc7274da-04ec-46ec-aa32-da7e47ca1335': 'Häggström M, Liver (transparent). Public domain. From Wikimedia Commons.', '0d3fb0a9-624e-4f35-bf53-b9ef91a26fa3': 'LadyofHats, Osmotic pressure on blood cells diagram. Public domain. From Wikimedia Commons.', '09319bf1-e82b-4d7b-8f69-9c09b9a9ab70': 'As a clinician, your first indication of changes to these cellular components will be illustrated by the signs and symptoms of your patient. Following this generalized assessment, you will begin to dissect out a clinical diagnosis by interpreting basic lab values. Each of these elements are indicative of molecular changes ultimately leading to the presentation you are challenged with.', 'b825122b-ef67-44f8-8e43-40a5e90d9718': 'How to read a CMP both clinically and biochemically will help hone the skills of diagnosis and maintenance of health status in patients. Additional laboratory tests such as a lipid profile, blood lactate, or urinalysis may also be ordered to supplement information from the CMP.', '95e43085-48dc-43bf-a6ab-0f3aeeccbabb': 'Deviations in any of these values can help determine changes in substrate availability, cofactors, and\xa0vitamin\xa0or enzymatic deficiencies. It will also help you better understand how biochemical pathways can influence clinical signs and symptoms.'}"
Figure 3.1,cell_bio/images/Figure 3.1.jpg,Figure 3.1: Overview of the fed state.,"Under these conditions, most tissues (liver, skeletal muscle, adipose, brain, and red blood cells) will increase glucose uptake and oxidation (table 3.1 and figure 3.1).","{'b6d2cfa0-de95-4c60-ac0f-7faaf4605c00': 'In the fed state, or postprandial, elevated glucose levels trigger the release of insulin from the pancreas. As insulin levels rise, there is an increase in glucose uptake, oxidation, and storage in peripheral tissues as well as increases in other anabolic pathways.', 'b30fe9bd-725d-4d25-9e4a-1607efcc11bb': 'Under these conditions, most tissues (liver, skeletal muscle, adipose, brain, and red blood cells) will increase glucose uptake and oxidation (table 3.1 and figure 3.1).', '5291e1f8-19cf-4b9e-a7e3-ae3a3b9a0b12': 'Each tissue will take up glucose in the fed state using one of the glucose transporters (GLUT) known to facilitate glucose transport across the plasma membrane. This family of proteins can be broadly categorized as insulin-independent and insulin-dependent transporters.', 'cf50ecaa-17fd-479a-8744-0cfbce1e3920': 'Table 3.1: Summary table of fuels used in the fed state and uptake methods for important tissues.', '130ada33-1bbd-4224-96c0-120eefb0d066': 'In the liver, glucose is taken up in an insulin-independent manner, and the activity of the following processes increased in the fed state are summarized in figure 3.1 and tables 3.1 and 3.2.', 'c2bbdb21-b5e1-4528-a6a9-a1bad9ad1f07': 'Lieberman, M., A. and Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 3: The Fasted State.', '965ffb94-bc92-413a-afc2-1300b985d8f5': 'Arm muscles anatomical. Public domain. From wpclipart.', 'bc7274da-04ec-46ec-aa32-da7e47ca1335': 'Häggström M, Liver (transparent). Public domain. From Wikimedia Commons.', '0d3fb0a9-624e-4f35-bf53-b9ef91a26fa3': 'LadyofHats, Osmotic pressure on blood cells diagram. Public domain. From Wikimedia Commons.', '09319bf1-e82b-4d7b-8f69-9c09b9a9ab70': 'As a clinician, your first indication of changes to these cellular components will be illustrated by the signs and symptoms of your patient. Following this generalized assessment, you will begin to dissect out a clinical diagnosis by interpreting basic lab values. Each of these elements are indicative of molecular changes ultimately leading to the presentation you are challenged with.', 'b825122b-ef67-44f8-8e43-40a5e90d9718': 'How to read a CMP both clinically and biochemically will help hone the skills of diagnosis and maintenance of health status in patients. Additional laboratory tests such as a lipid profile, blood lactate, or urinalysis may also be ordered to supplement information from the CMP.', '95e43085-48dc-43bf-a6ab-0f3aeeccbabb': 'Deviations in any of these values can help determine changes in substrate availability, cofactors, and\xa0vitamin\xa0or enzymatic deficiencies. It will also help you better understand how biochemical pathways can influence clinical signs and symptoms.'}"
Figure 3.2,cell_bio/images/Figure 3.2.jpg,Figure 3.2: Overview of fasted state metabolism.,"The primary role of the liver in the fasted state is to synthesize and release glucose. To facilitate this task, the liver will use circulating free fatty acids as the primary fuel source to generate energy (ATP) for these homeostatic processes. (These processes are summarized in figure 3.2 and tables 3.3 and 3.4)","{'7a3ec35d-40b2-4690-9234-1ee40ac510d9': 'Approximately two\xa0hours after a meal, the decrease in serum glucose levels will lead to decreased insulin production in the pancreas. At this point in fasted state metabolism, the insulin to glucagon ratio becomes\xa0 less than 1 (insulin low; glucagon high) with an additional increase of cortisol and epinephrine. Under these conditions tissues will transition to utilizing alternative fuels for energy as a means of maintaining glucose homeostasis. Fasted state metabolism will have limited impact on the oxidation of glucose by the brain and red blood cells, but it will lead to an increase in fatty acid oxidation by both the skeletal muscle and the liver (figure 3.6). The fatty acids oxidized by these tissues are released through the process of epinephrine-mediated lipolysis from the adipose. In the fasted state, the liver will primarily release glucose using both gluconeogenesis and glycogenolysis for the maintenance of blood glucose.', '301f19d4-f160-4e83-9ec8-21cb3ddbeddf': 'Table 3.3: Summary table of fuels used in the fasted state and the pathways providing the fuel source.', 'd919abd4-f28c-4e7d-b184-33b754662fdd': 'The primary role of the liver in the fasted state is to synthesize and release glucose. To facilitate this task, the liver\xa0will use circulating free fatty acids as the primary fuel source to generate energy (ATP) for these homeostatic processes. (These processes are summarized in figure 3.2 and tables 3.3 and 3.4)', '3b9f1182-e156-4062-8117-dfb0515afdb0': 'The red blood cell lacks mitochondria, therefore it oxidizes glucose under both fed and fasted conditions. The metabolism of this tissue remains largely unchanged.', '51c87026-5818-40cb-8807-fa467ae336a6': 'The brain will oxidize glucose under most conditions with the exception of starvation states. Under normal fasting conditions, although ketones will be synthesized, the brain will not transition to utilizing them as a predominant source of fuel until extended fasting has occurred (days).', 'ff9e2a78-f6bc-4d5f-9a95-1119a4863e17': 'The skeletal muscle will increase uptake of fatty acids and ketones.', 'db1d6849-6e4a-4ee1-929a-184801a22236': 'The most important process in the adipose tissue during the fasted state is lipolysis.', 'c23f64eb-49f7-42d1-bbe7-77d0485d3a7f': 'Table 3.4: Summary of metabolism during the fasted state.', '874810fd-adc1-498c-8a3a-347765c6e50e': '3.1 References and resources', 'fc45a092-3e09-4c54-8fb6-958af0bd3fd7': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 24: Fed Fast Cycle.', '6d7664aa-702b-428d-aaad-63c5b00529a8': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 91, 324–325', 'c2bbdb21-b5e1-4528-a6a9-a1bad9ad1f07': 'Lieberman, M., A. and Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 2: The Fed or Absorptive State, Chapter 3: The Fasted State.', '965ffb94-bc92-413a-afc2-1300b985d8f5': 'Arm muscles anatomical. Public domain. From wpclipart.', 'bc7274da-04ec-46ec-aa32-da7e47ca1335': 'Häggström M, Liver (transparent). Public domain. From Wikimedia Commons.', '0d3fb0a9-624e-4f35-bf53-b9ef91a26fa3': 'LadyofHats, Osmotic pressure on blood cells diagram. Public domain. From Wikimedia Commons.', '09319bf1-e82b-4d7b-8f69-9c09b9a9ab70': 'As a clinician, your first indication of changes to these cellular components will be illustrated by the signs and symptoms of your patient. Following this generalized assessment, you will begin to dissect out a clinical diagnosis by interpreting basic lab values. Each of these elements are indicative of molecular changes ultimately leading to the presentation you are challenged with.', 'b825122b-ef67-44f8-8e43-40a5e90d9718': 'How to read a CMP both clinically and biochemically will help hone the skills of diagnosis and maintenance of health status in patients. Additional laboratory tests such as a lipid profile, blood lactate, or urinalysis may also be ordered to supplement information from the CMP.', '95e43085-48dc-43bf-a6ab-0f3aeeccbabb': 'Deviations in any of these values can help determine changes in substrate availability, cofactors, and\xa0vitamin\xa0or enzymatic deficiencies. It will also help you better understand how biochemical pathways can influence clinical signs and symptoms.'}"
Figure 2.1,cell_bio/images/Figure 2.1.jpg,Figure 2.1: Heme degradation.,"Bilirubin – Bilirubin is a waste product produced by the degradation of heme. Heme degradation within the liver is a normal part of red blood cell turnover, but elevated bilirubin could also be indicative of excessive hemolysis (due to deficiencies in NAPDH or increased oxidative stress) or biliary obstructions. Bilirubin values can be reported as direct (conjugated) or indirect (unconjugated) bilirubin. As conjugation takes place in the liver, decreased conjugated bilirubin or increased unconjugated bilirubin would suggest liver dysfunction (figure 2.1).","{'daa4f6b2-27c6-4e7f-85af-54bbb05c2bc6': 'Alkaline phosphatase (ALP) – ALP is an enzyme found in the liver and other tissues such as bone. Elevated levels of ALP are most commonly caused by liver disease or other pathologies that increase cell damage leading to the release of ALP in the blood. Other disorders that impact bone growth may also increase ALP.', 'f92bf38c-fbce-49d1-9a3d-39875bdced7f': 'Alanine amino transferase (ALT) – ALT is an enzyme found predominantly in the liver and kidney. It is important in movement of ammonia (through the process of transamination) in tissues, and an elevation of ALT in circulation suggests liver damage (or potentially muscle damage) (section 5.3).', '4115f0c6-83ee-419c-898e-f77232222093': 'Aspartate amino transferase (AST) – AST is also a transferase needed in nitrogen metabolism found especially within the heart and liver. It is also a useful test for detecting liver damage. The ratio of ALT/AST can be used to distinguish between disorders such as alcoholic versus nonalcoholic fatty liver disease (section 5.3).', 'a63aa7ac-62b9-44e4-8fca-6ee7a595a39b': 'Bilirubin – Bilirubin is a waste product produced by the degradation of heme. Heme degradation within the liver is a normal part of red blood cell turnover, but elevated bilirubin could also be indicative of excessive hemolysis (due to deficiencies in NAPDH or increased oxidative stress) or biliary obstructions. Bilirubin values can be reported as direct (conjugated) or indirect (unconjugated) bilirubin. As conjugation takes place in the liver, decreased conjugated bilirubin or increased\xa0unconjugated bilirubin would suggest liver dysfunction (figure 2.1).', 'ce24cf01-6e56-475f-ae30-bb941c7cf876': 'Much like the CMP, the chemical analysis of a urine sample can be very indicative of biochemical derangement. A review of the following components is\xa0helpful in making a clinical diagnosis.', '4bcad1ae-be4c-4d76-836b-cd4eb5389dd2': 'Specific gravity (SG) – Specific gravity is a measure of urine concentration. This test simply indicates how concentrated the urine is.', '1b479ebf-4bca-4639-9cd6-439b3140713b': 'pH – Urine is typically slightly acidic, about pH 6, but can range from 4.5 to 8. The kidneys play an important role in maintaining the acid–base balance of the body. Therefore, any condition that produces acids or bases in the body, such as acidosis or alkalosis, or the ingestion of acidic or basic foods, can directly affect urine pH.', 'c87a34d8-6da0-46d6-b0c6-daa20cee8c31': 'Protein – The protein test provides an estimate of the amount of albumin in the urine. Normally, there should be no protein (or a small amount of protein) in the urine. When urine protein is elevated, a person has a condition called proteinuria; this could be caused by a variety of health conditions. Healthy people can have temporary or persistent proteinuria due to stress, exercise, fever, aspirin therapy, or exposure to cold, for example.', '9c043a93-dccb-484a-8440-73a46cb3b574': 'Glucose – Glucose is normally not present in urine. When glucose is present, the condition is called glucosuria. This condition can result from either an excessively high glucose level in the blood, such as may be seen in individuals with uncontrolled diabetes. Other reducing sugars, galactose or fructose, may also be present in the urine if a metabolic deficiency occurs (section 9.1).', 'ede3c16b-b3ed-45a5-9a41-c0c14b960abf': 'Some other conditions that can cause glucosuria include hormonal disorders, liver disease, medications, and pregnancy. When glucosuria occurs, other tests such as a fasting blood glucose test are usually performed to further identify the specific cause.', 'a66690ff-d6b3-44b4-bd16-c6cbe0989de2': 'Ketones – Ketones are also not normally found in the urine. They are intermediate products of fat metabolism and can be produced when an individual does not eat enough carbohydrates such as in fasting conditions or high-protein diets. When carbohydrates are not available, the body metabolizes fat to generate ATP for baseline metabolic function. Strenuous exercise, exposure to cold, frequent, prolonged vomiting, and several digestive system diseases can also increase fat metabolism, resulting in ketonuria (section 5.2).', '127df023-2b3f-4243-ab01-2ea54fc5bff2': 'In a person who has diabetes, ketones in urine may be an early indication of insufficient insulin. Insufficient insulin response can result in impaired glucose oxidation and consequently results in aberrant fat metabolism. Oxidation of fatty acids provides substrate for ketogenesis, which can cause ketosis and potentially progress\xa0to ketoacidosis, a form of metabolic acidosis. Excess ketones and glucose are dumped into the urine by the kidneys in an effort to flush them from the body.', '33e94050-5429-46b5-a7c5-4355b5f2a04c': 'Hemoglobin and myoglobin – The presence of hemoglobin in urine indicates blood in the urine (known as hematuria).', '89d4adf9-953d-4c40-a578-b8b5712967fa': 'A small number of RBCs are normally present in urine, however, as these numbers elevate, this will result in a positive test result. These results are interpreted with the microscopic exam. For example, a positive test result here with no visible RBCs in the urine would suggest the presence of myoglobin only, which could be due to strenuous exercise or muscle damage.', '5d289da4-a41d-411c-a7e7-3ba2460ebe28': 'Leukocyte esterase – Leukocyte esterase is an enzyme present in most white blood cells (WBCs). A few white blood cells are normally present in urine, however, when the number of WBCs in urine increases significantly, this screening test will become positive. When this test is positive and/or the WBC count in urine is high, it may indicate that there is inflammation in the urinary tract or kidneys.', 'aeea09c1-77a7-40c9-9800-c26633a1fa81': 'Nitrite – Many normal bacteria can convert nitrate (normally present in urine) to nitrite (not normally present in urine). When bacteria are present in the urinary tract, they can cause a urinary tract infection, which could be diagnosed by a positive nitrite test result.', 'e4e951cc-30ca-4a6e-9aff-9c28261beecd': 'Bilirubin – Bilirubin is not present in the urine of healthy individuals (figure 2.1). The presence of bilirubin in urine is an early indicator of liver disease and can occur before clinical symptoms such as jaundice develop. Only conjugated bilirubin is present in the urine.', '7c9d42da-a575-4c7d-a0fe-f52ec5a95263': 'Urobilinogen – Urobilinogen is normally present in urine in low concentrations. It is formed in the intestine from bilirubin, and a portion of it is absorbed back into the blood. Positive test results may indicate liver diseases such as viral hepatitis, cirrhosis, liver damage due to drugs or toxic substances, or conditions associated with increased RBC destruction (hemolytic anemia).', 'b80f87cd-8fad-4be6-a728-69888ef213f0': '2.1 References and resources', 'c0c291bb-e400-4f98-a6be-34061f2e62df': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 27: Nutrition: Overview, Chapter 28: Micronutrients: Vitamins, Chapter 29: Micronutrients: Minerals.', '76290482-5ce0-4971-afb3-8f886f36028c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 65–71.', '9c9775e7-db3b-493a-9bc5-0e883cc64b13': '2.2 Vitamins as Coenzymes'}"
Figure 2.2,cell_bio/images/Figure 2.2.jpg,Figure 2.2: Reaction catalyzed by lactate dehydrogenase.,"Serum lactate levels may also be measured in conjunction with a complete metabolic panel. Serum lactate should be negligible under normal conditions, however, elevated lactate could be suggestive of excessive anaerobic metabolism, such as is the case in intense exercise or deficiency in oxygen transport caused by ischemic injury. This could also be caused by inappropriate diversion of substrate such as is the case in some enzymatic deficiencies (pyruvate dehydrogenase deficiency) or changes in NADH levels (figure 2.2).","{'c827d3f2-88d2-4b93-9996-ea3bb4eb386e': 'Lactate is primarily produced through the Cori cycle or from anaerobic glucose oxidation. (Note: The Cori cycle, or lactic acid cycle, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscle or RBC travels to the liver and is converted to glucose. The glucose returns to the peripheral tissues and is metabolized back to lactate.)\xa0Once in the liver, lactate can be oxidized back to pyruvate through the reverse reaction catalyzed by lactate dehydrogenase (figure 5.3).', 'a1bd4d19-e758-479c-b85d-67408c03c539': 'Serum lactate levels may also be measured in conjunction with a complete metabolic panel. Serum lactate should be negligible under normal conditions, however, elevated lactate could be suggestive of excessive anaerobic metabolism, such as is the case in intense exercise or deficiency in oxygen transport caused by ischemic injury. This could also be caused by inappropriate diversion of substrate such as is the case in some enzymatic deficiencies (pyruvate dehydrogenase deficiency) or changes in NADH levels (figure 2.2).', 'ce24cf01-6e56-475f-ae30-bb941c7cf876': 'Much like the CMP, the chemical analysis of a urine sample can be very indicative of biochemical derangement. A review of the following components is\xa0helpful in making a clinical diagnosis.', '4bcad1ae-be4c-4d76-836b-cd4eb5389dd2': 'Specific gravity (SG) – Specific gravity is a measure of urine concentration. This test simply indicates how concentrated the urine is.', '1b479ebf-4bca-4639-9cd6-439b3140713b': 'pH – Urine is typically slightly acidic, about pH 6, but can range from 4.5 to 8. The kidneys play an important role in maintaining the acid–base balance of the body. Therefore, any condition that produces acids or bases in the body, such as acidosis or alkalosis, or the ingestion of acidic or basic foods, can directly affect urine pH.', 'c87a34d8-6da0-46d6-b0c6-daa20cee8c31': 'Protein – The protein test provides an estimate of the amount of albumin in the urine. Normally, there should be no protein (or a small amount of protein) in the urine. When urine protein is elevated, a person has a condition called proteinuria; this could be caused by a variety of health conditions. Healthy people can have temporary or persistent proteinuria due to stress, exercise, fever, aspirin therapy, or exposure to cold, for example.', '9c043a93-dccb-484a-8440-73a46cb3b574': 'Glucose – Glucose is normally not present in urine. When glucose is present, the condition is called glucosuria. This condition can result from either an excessively high glucose level in the blood, such as may be seen in individuals with uncontrolled diabetes. Other reducing sugars, galactose or fructose, may also be present in the urine if a metabolic deficiency occurs (section 9.1).', 'ede3c16b-b3ed-45a5-9a41-c0c14b960abf': 'Some other conditions that can cause glucosuria include hormonal disorders, liver disease, medications, and pregnancy. When glucosuria occurs, other tests such as a fasting blood glucose test are usually performed to further identify the specific cause.', 'a66690ff-d6b3-44b4-bd16-c6cbe0989de2': 'Ketones – Ketones are also not normally found in the urine. They are intermediate products of fat metabolism and can be produced when an individual does not eat enough carbohydrates such as in fasting conditions or high-protein diets. When carbohydrates are not available, the body metabolizes fat to generate ATP for baseline metabolic function. Strenuous exercise, exposure to cold, frequent, prolonged vomiting, and several digestive system diseases can also increase fat metabolism, resulting in ketonuria (section 5.2).', '127df023-2b3f-4243-ab01-2ea54fc5bff2': 'In a person who has diabetes, ketones in urine may be an early indication of insufficient insulin. Insufficient insulin response can result in impaired glucose oxidation and consequently results in aberrant fat metabolism. Oxidation of fatty acids provides substrate for ketogenesis, which can cause ketosis and potentially progress\xa0to ketoacidosis, a form of metabolic acidosis. Excess ketones and glucose are dumped into the urine by the kidneys in an effort to flush them from the body.', '33e94050-5429-46b5-a7c5-4355b5f2a04c': 'Hemoglobin and myoglobin – The presence of hemoglobin in urine indicates blood in the urine (known as hematuria).', '89d4adf9-953d-4c40-a578-b8b5712967fa': 'A small number of RBCs are normally present in urine, however, as these numbers elevate, this will result in a positive test result. These results are interpreted with the microscopic exam. For example, a positive test result here with no visible RBCs in the urine would suggest the presence of myoglobin only, which could be due to strenuous exercise or muscle damage.', '5d289da4-a41d-411c-a7e7-3ba2460ebe28': 'Leukocyte esterase – Leukocyte esterase is an enzyme present in most white blood cells (WBCs). A few white blood cells are normally present in urine, however, when the number of WBCs in urine increases significantly, this screening test will become positive. When this test is positive and/or the WBC count in urine is high, it may indicate that there is inflammation in the urinary tract or kidneys.', 'aeea09c1-77a7-40c9-9800-c26633a1fa81': 'Nitrite – Many normal bacteria can convert nitrate (normally present in urine) to nitrite (not normally present in urine). When bacteria are present in the urinary tract, they can cause a urinary tract infection, which could be diagnosed by a positive nitrite test result.', 'e4e951cc-30ca-4a6e-9aff-9c28261beecd': 'Bilirubin – Bilirubin is not present in the urine of healthy individuals (figure 2.1). The presence of bilirubin in urine is an early indicator of liver disease and can occur before clinical symptoms such as jaundice develop. Only conjugated bilirubin is present in the urine.', '7c9d42da-a575-4c7d-a0fe-f52ec5a95263': 'Urobilinogen – Urobilinogen is normally present in urine in low concentrations. It is formed in the intestine from bilirubin, and a portion of it is absorbed back into the blood. Positive test results may indicate liver diseases such as viral hepatitis, cirrhosis, liver damage due to drugs or toxic substances, or conditions associated with increased RBC destruction (hemolytic anemia).', 'b80f87cd-8fad-4be6-a728-69888ef213f0': '2.1 References and resources', 'c0c291bb-e400-4f98-a6be-34061f2e62df': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 27: Nutrition: Overview, Chapter 28: Micronutrients: Vitamins, Chapter 29: Micronutrients: Minerals.', '76290482-5ce0-4971-afb3-8f886f36028c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 65–71.', '9c9775e7-db3b-493a-9bc5-0e883cc64b13': '2.2 Vitamins as Coenzymes'}"
Figure 2.1,cell_bio/images/Figure 2.1.jpg,Figure 2.1: Heme degradation.,"Bilirubin – Bilirubin is a waste product produced by the degradation of heme. Heme degradation within the liver is a normal part of red blood cell turnover, but elevated bilirubin could also be indicative of excessive hemolysis (due to deficiencies in NAPDH or increased oxidative stress) or biliary obstructions. Bilirubin values can be reported as direct (conjugated) or indirect (unconjugated) bilirubin. As conjugation takes place in the liver, decreased conjugated bilirubin or increased unconjugated bilirubin would suggest liver dysfunction (figure 2.1).","{'daa4f6b2-27c6-4e7f-85af-54bbb05c2bc6': 'Alkaline phosphatase (ALP) – ALP is an enzyme found in the liver and other tissues such as bone. Elevated levels of ALP are most commonly caused by liver disease or other pathologies that increase cell damage leading to the release of ALP in the blood. Other disorders that impact bone growth may also increase ALP.', 'f92bf38c-fbce-49d1-9a3d-39875bdced7f': 'Alanine amino transferase (ALT) – ALT is an enzyme found predominantly in the liver and kidney. It is important in movement of ammonia (through the process of transamination) in tissues, and an elevation of ALT in circulation suggests liver damage (or potentially muscle damage) (section 5.3).', '4115f0c6-83ee-419c-898e-f77232222093': 'Aspartate amino transferase (AST) – AST is also a transferase needed in nitrogen metabolism found especially within the heart and liver. It is also a useful test for detecting liver damage. The ratio of ALT/AST can be used to distinguish between disorders such as alcoholic versus nonalcoholic fatty liver disease (section 5.3).', 'a63aa7ac-62b9-44e4-8fca-6ee7a595a39b': 'Bilirubin – Bilirubin is a waste product produced by the degradation of heme. Heme degradation within the liver is a normal part of red blood cell turnover, but elevated bilirubin could also be indicative of excessive hemolysis (due to deficiencies in NAPDH or increased oxidative stress) or biliary obstructions. Bilirubin values can be reported as direct (conjugated) or indirect (unconjugated) bilirubin. As conjugation takes place in the liver, decreased conjugated bilirubin or increased\xa0unconjugated bilirubin would suggest liver dysfunction (figure 2.1).', 'ce24cf01-6e56-475f-ae30-bb941c7cf876': 'Much like the CMP, the chemical analysis of a urine sample can be very indicative of biochemical derangement. A review of the following components is\xa0helpful in making a clinical diagnosis.', '4bcad1ae-be4c-4d76-836b-cd4eb5389dd2': 'Specific gravity (SG) – Specific gravity is a measure of urine concentration. This test simply indicates how concentrated the urine is.', '1b479ebf-4bca-4639-9cd6-439b3140713b': 'pH – Urine is typically slightly acidic, about pH 6, but can range from 4.5 to 8. The kidneys play an important role in maintaining the acid–base balance of the body. Therefore, any condition that produces acids or bases in the body, such as acidosis or alkalosis, or the ingestion of acidic or basic foods, can directly affect urine pH.', 'c87a34d8-6da0-46d6-b0c6-daa20cee8c31': 'Protein – The protein test provides an estimate of the amount of albumin in the urine. Normally, there should be no protein (or a small amount of protein) in the urine. When urine protein is elevated, a person has a condition called proteinuria; this could be caused by a variety of health conditions. Healthy people can have temporary or persistent proteinuria due to stress, exercise, fever, aspirin therapy, or exposure to cold, for example.', '9c043a93-dccb-484a-8440-73a46cb3b574': 'Glucose – Glucose is normally not present in urine. When glucose is present, the condition is called glucosuria. This condition can result from either an excessively high glucose level in the blood, such as may be seen in individuals with uncontrolled diabetes. Other reducing sugars, galactose or fructose, may also be present in the urine if a metabolic deficiency occurs (section 9.1).', 'ede3c16b-b3ed-45a5-9a41-c0c14b960abf': 'Some other conditions that can cause glucosuria include hormonal disorders, liver disease, medications, and pregnancy. When glucosuria occurs, other tests such as a fasting blood glucose test are usually performed to further identify the specific cause.', 'a66690ff-d6b3-44b4-bd16-c6cbe0989de2': 'Ketones – Ketones are also not normally found in the urine. They are intermediate products of fat metabolism and can be produced when an individual does not eat enough carbohydrates such as in fasting conditions or high-protein diets. When carbohydrates are not available, the body metabolizes fat to generate ATP for baseline metabolic function. Strenuous exercise, exposure to cold, frequent, prolonged vomiting, and several digestive system diseases can also increase fat metabolism, resulting in ketonuria (section 5.2).', '127df023-2b3f-4243-ab01-2ea54fc5bff2': 'In a person who has diabetes, ketones in urine may be an early indication of insufficient insulin. Insufficient insulin response can result in impaired glucose oxidation and consequently results in aberrant fat metabolism. Oxidation of fatty acids provides substrate for ketogenesis, which can cause ketosis and potentially progress\xa0to ketoacidosis, a form of metabolic acidosis. Excess ketones and glucose are dumped into the urine by the kidneys in an effort to flush them from the body.', '33e94050-5429-46b5-a7c5-4355b5f2a04c': 'Hemoglobin and myoglobin – The presence of hemoglobin in urine indicates blood in the urine (known as hematuria).', '89d4adf9-953d-4c40-a578-b8b5712967fa': 'A small number of RBCs are normally present in urine, however, as these numbers elevate, this will result in a positive test result. These results are interpreted with the microscopic exam. For example, a positive test result here with no visible RBCs in the urine would suggest the presence of myoglobin only, which could be due to strenuous exercise or muscle damage.', '5d289da4-a41d-411c-a7e7-3ba2460ebe28': 'Leukocyte esterase – Leukocyte esterase is an enzyme present in most white blood cells (WBCs). A few white blood cells are normally present in urine, however, when the number of WBCs in urine increases significantly, this screening test will become positive. When this test is positive and/or the WBC count in urine is high, it may indicate that there is inflammation in the urinary tract or kidneys.', 'aeea09c1-77a7-40c9-9800-c26633a1fa81': 'Nitrite – Many normal bacteria can convert nitrate (normally present in urine) to nitrite (not normally present in urine). When bacteria are present in the urinary tract, they can cause a urinary tract infection, which could be diagnosed by a positive nitrite test result.', 'e4e951cc-30ca-4a6e-9aff-9c28261beecd': 'Bilirubin – Bilirubin is not present in the urine of healthy individuals (figure 2.1). The presence of bilirubin in urine is an early indicator of liver disease and can occur before clinical symptoms such as jaundice develop. Only conjugated bilirubin is present in the urine.', '7c9d42da-a575-4c7d-a0fe-f52ec5a95263': 'Urobilinogen – Urobilinogen is normally present in urine in low concentrations. It is formed in the intestine from bilirubin, and a portion of it is absorbed back into the blood. Positive test results may indicate liver diseases such as viral hepatitis, cirrhosis, liver damage due to drugs or toxic substances, or conditions associated with increased RBC destruction (hemolytic anemia).', 'b80f87cd-8fad-4be6-a728-69888ef213f0': '2.1 References and resources', 'c0c291bb-e400-4f98-a6be-34061f2e62df': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 27: Nutrition: Overview, Chapter 28: Micronutrients: Vitamins, Chapter 29: Micronutrients: Minerals.', '76290482-5ce0-4971-afb3-8f886f36028c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 65–71.', '9c9775e7-db3b-493a-9bc5-0e883cc64b13': '2.2 Vitamins as Coenzymes'}"
Figure 2.2,cell_bio/images/Figure 2.2.jpg,Figure 2.2: Reaction catalyzed by lactate dehydrogenase.,"Serum lactate levels may also be measured in conjunction with a complete metabolic panel. Serum lactate should be negligible under normal conditions, however, elevated lactate could be suggestive of excessive anaerobic metabolism, such as is the case in intense exercise or deficiency in oxygen transport caused by ischemic injury. This could also be caused by inappropriate diversion of substrate such as is the case in some enzymatic deficiencies (pyruvate dehydrogenase deficiency) or changes in NADH levels (figure 2.2).","{'c827d3f2-88d2-4b93-9996-ea3bb4eb386e': 'Lactate is primarily produced through the Cori cycle or from anaerobic glucose oxidation. (Note: The Cori cycle, or lactic acid cycle, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscle or RBC travels to the liver and is converted to glucose. The glucose returns to the peripheral tissues and is metabolized back to lactate.)\xa0Once in the liver, lactate can be oxidized back to pyruvate through the reverse reaction catalyzed by lactate dehydrogenase (figure 5.3).', 'a1bd4d19-e758-479c-b85d-67408c03c539': 'Serum lactate levels may also be measured in conjunction with a complete metabolic panel. Serum lactate should be negligible under normal conditions, however, elevated lactate could be suggestive of excessive anaerobic metabolism, such as is the case in intense exercise or deficiency in oxygen transport caused by ischemic injury. This could also be caused by inappropriate diversion of substrate such as is the case in some enzymatic deficiencies (pyruvate dehydrogenase deficiency) or changes in NADH levels (figure 2.2).', 'ce24cf01-6e56-475f-ae30-bb941c7cf876': 'Much like the CMP, the chemical analysis of a urine sample can be very indicative of biochemical derangement. A review of the following components is\xa0helpful in making a clinical diagnosis.', '4bcad1ae-be4c-4d76-836b-cd4eb5389dd2': 'Specific gravity (SG) – Specific gravity is a measure of urine concentration. This test simply indicates how concentrated the urine is.', '1b479ebf-4bca-4639-9cd6-439b3140713b': 'pH – Urine is typically slightly acidic, about pH 6, but can range from 4.5 to 8. The kidneys play an important role in maintaining the acid–base balance of the body. Therefore, any condition that produces acids or bases in the body, such as acidosis or alkalosis, or the ingestion of acidic or basic foods, can directly affect urine pH.', 'c87a34d8-6da0-46d6-b0c6-daa20cee8c31': 'Protein – The protein test provides an estimate of the amount of albumin in the urine. Normally, there should be no protein (or a small amount of protein) in the urine. When urine protein is elevated, a person has a condition called proteinuria; this could be caused by a variety of health conditions. Healthy people can have temporary or persistent proteinuria due to stress, exercise, fever, aspirin therapy, or exposure to cold, for example.', '9c043a93-dccb-484a-8440-73a46cb3b574': 'Glucose – Glucose is normally not present in urine. When glucose is present, the condition is called glucosuria. This condition can result from either an excessively high glucose level in the blood, such as may be seen in individuals with uncontrolled diabetes. Other reducing sugars, galactose or fructose, may also be present in the urine if a metabolic deficiency occurs (section 9.1).', 'ede3c16b-b3ed-45a5-9a41-c0c14b960abf': 'Some other conditions that can cause glucosuria include hormonal disorders, liver disease, medications, and pregnancy. When glucosuria occurs, other tests such as a fasting blood glucose test are usually performed to further identify the specific cause.', 'a66690ff-d6b3-44b4-bd16-c6cbe0989de2': 'Ketones – Ketones are also not normally found in the urine. They are intermediate products of fat metabolism and can be produced when an individual does not eat enough carbohydrates such as in fasting conditions or high-protein diets. When carbohydrates are not available, the body metabolizes fat to generate ATP for baseline metabolic function. Strenuous exercise, exposure to cold, frequent, prolonged vomiting, and several digestive system diseases can also increase fat metabolism, resulting in ketonuria (section 5.2).', '127df023-2b3f-4243-ab01-2ea54fc5bff2': 'In a person who has diabetes, ketones in urine may be an early indication of insufficient insulin. Insufficient insulin response can result in impaired glucose oxidation and consequently results in aberrant fat metabolism. Oxidation of fatty acids provides substrate for ketogenesis, which can cause ketosis and potentially progress\xa0to ketoacidosis, a form of metabolic acidosis. Excess ketones and glucose are dumped into the urine by the kidneys in an effort to flush them from the body.', '33e94050-5429-46b5-a7c5-4355b5f2a04c': 'Hemoglobin and myoglobin – The presence of hemoglobin in urine indicates blood in the urine (known as hematuria).', '89d4adf9-953d-4c40-a578-b8b5712967fa': 'A small number of RBCs are normally present in urine, however, as these numbers elevate, this will result in a positive test result. These results are interpreted with the microscopic exam. For example, a positive test result here with no visible RBCs in the urine would suggest the presence of myoglobin only, which could be due to strenuous exercise or muscle damage.', '5d289da4-a41d-411c-a7e7-3ba2460ebe28': 'Leukocyte esterase – Leukocyte esterase is an enzyme present in most white blood cells (WBCs). A few white blood cells are normally present in urine, however, when the number of WBCs in urine increases significantly, this screening test will become positive. When this test is positive and/or the WBC count in urine is high, it may indicate that there is inflammation in the urinary tract or kidneys.', 'aeea09c1-77a7-40c9-9800-c26633a1fa81': 'Nitrite – Many normal bacteria can convert nitrate (normally present in urine) to nitrite (not normally present in urine). When bacteria are present in the urinary tract, they can cause a urinary tract infection, which could be diagnosed by a positive nitrite test result.', 'e4e951cc-30ca-4a6e-9aff-9c28261beecd': 'Bilirubin – Bilirubin is not present in the urine of healthy individuals (figure 2.1). The presence of bilirubin in urine is an early indicator of liver disease and can occur before clinical symptoms such as jaundice develop. Only conjugated bilirubin is present in the urine.', '7c9d42da-a575-4c7d-a0fe-f52ec5a95263': 'Urobilinogen – Urobilinogen is normally present in urine in low concentrations. It is formed in the intestine from bilirubin, and a portion of it is absorbed back into the blood. Positive test results may indicate liver diseases such as viral hepatitis, cirrhosis, liver damage due to drugs or toxic substances, or conditions associated with increased RBC destruction (hemolytic anemia).', 'b80f87cd-8fad-4be6-a728-69888ef213f0': '2.1 References and resources', 'c0c291bb-e400-4f98-a6be-34061f2e62df': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 27: Nutrition: Overview, Chapter 28: Micronutrients: Vitamins, Chapter 29: Micronutrients: Minerals.', '76290482-5ce0-4971-afb3-8f886f36028c': 'Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 65–71.', '9c9775e7-db3b-493a-9bc5-0e883cc64b13': '2.2 Vitamins as Coenzymes'}"
Figure 2.3,cell_bio/images/Figure 2.3.jpg,Figure 2.3: Mechanism of action of vitamin A.,Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.,"{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 2.4,cell_bio/images/Figure 2.4.jpg,,Figure 2.4: Vitamin K stimulates the maturation of clotting factors.,"{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.2,cell_bio/images/Figure 1.2.jpg,Figure 1.2: Chart of amino acids.,Amino acids can be grouped largely by the functionality of their R-group (figure 1.2).,"{'2b57c575-c182-45ac-8825-0adb3ee5bfde': 'Table 2.3 adapted from Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017.', 'a1b327f8-105f-4455-970f-d5dc431708e5': 'Amino acids can be grouped largely by the functionality of their R-group (figure 1.2).', '27099d91-541a-4f2d-8c75-4d2e09c8c189': 'Although it is not essential to memorize the structures of the amino acids, a strong understanding of their general characteristics will be very helpful.', 'da24e3df-cc71-4f69-bb99-2a6f76add162': 'Amino acids with uncharged polar R-groups may participate in hydrogen bonding and undergo modifications such as phosphorylation. Tyrosine, serine, and threonine\xa0all have a hydroxyl group\xa0within the R-group, and they can also be readily modified by kinase-mediated phosphorylation.', '5ab9aa34-36fb-487e-8f7a-3e9dab933477': 'Some amino acids are charged at a physiological pH and can be acidic or basic. These side chains may donate or accept protons, respectively, and the most notable charged amino acid is histidine, which can function as a buffer at a physiological pH.', '3067974d-a013-43af-804d-759c9295e62c': '1.1 References and resources', '9bbc330e-7628-4a8a-bea3-1277e24382d9': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 1: Amino Acids, Chapter 2: Protein Structure.', '71e8030c-0f45-4b0d-81e8-5f3946e34f17': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 6: Amino Acids in Proteins, Chapter 8: Enzymes as Catalysts, Chapter 9: Regulation of Enzymes.', '8cda99ef-1df2-4d64-b8aa-1bd12ce5ebb6': '1.2 Enzyme Kinetics', '22762992-8159-4f33-a756-379751eb176b': 'Many translated proteins are also enzymes with\xa0a specific metabolic function within the cell. Enzymes help reduce the amount of transition state energy required for a reaction to move forward through several mechanisms:', 'fc64a696-874c-4f51-9e7e-6ed6c917d9b4': 'The kinetics of enzyme-catalyzed reactions is mainly determined by the properties of the catalyst. Like all catalysts, the enzyme [E]\xa0creates a new reaction pathway. Initially, the substrate\xa0[S]\xa0is bound to the free enzyme [ES] (figure 1.3).', '7a3d5064-3a17-423e-9b8c-b79ccc4c312b': 'The rate of this enzyme reaction can be described by the Michaelis–Menten equation, which relates the the initial velocity (vi) to the concentration of substrate [S] and the two parameters Km and Vmax. The Vmax is defined as the maximal velocity that can be achieved at an infinite substrate concentration, while the Km is defined as the substrate concentration needed to reach 1/2 Vmax. The Michaelis constant (Km) characterizes the affinity of the enzyme for a substrate. A high affinity of the enzyme for a substrate therefore leads to a low Km value, and vice versa (figure 1.4).', '6285275b-cc7f-4a99-bd01-83bda78e0599': 'The Michaelis‒Menten model contains simplifying assumptions (substrate binding is in equilibrium, formation of [P] is irreversible, [E] and [ES] are the only enzyme forms).', '94624dd8-fa14-4520-8520-4e57fa1a595f': 'Since vi approaches Vmax asymptotically, it is difficult to read off reliable values for Vmax or Km from diagrams plotting v against [S] (figure 1.4). To alleviate this issue, the Michaelis‒Menten equation can be arranged in such a way that the measured points lie on a straight line. In the Lineweaver‒Burk plot, 1/v is plotted against 1/[S]. The intersections of the line of best fit with the axes then produce 1/Vmax and −1/Km (figure 1.5).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.1,cell_bio/images/Figure 1.1.jpg,,Figure 1.1: Basic structure of amino acids and ionization.,"{'da24e3df-cc71-4f69-bb99-2a6f76add162': 'Amino acids with uncharged polar R-groups may participate in hydrogen bonding and undergo modifications such as phosphorylation. Tyrosine, serine, and threonine\xa0all have a hydroxyl group\xa0within the R-group, and they can also be readily modified by kinase-mediated phosphorylation.', '5ab9aa34-36fb-487e-8f7a-3e9dab933477': 'Some amino acids are charged at a physiological pH and can be acidic or basic. These side chains may donate or accept protons, respectively, and the most notable charged amino acid is histidine, which can function as a buffer at a physiological pH.', '3067974d-a013-43af-804d-759c9295e62c': '1.1 References and resources', '9bbc330e-7628-4a8a-bea3-1277e24382d9': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 1: Amino Acids, Chapter 2: Protein Structure.', '71e8030c-0f45-4b0d-81e8-5f3946e34f17': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 6: Amino Acids in Proteins, Chapter 8: Enzymes as Catalysts, Chapter 9: Regulation of Enzymes.', '8cda99ef-1df2-4d64-b8aa-1bd12ce5ebb6': '1.2 Enzyme Kinetics', '22762992-8159-4f33-a756-379751eb176b': 'Many translated proteins are also enzymes with\xa0a specific metabolic function within the cell. Enzymes help reduce the amount of transition state energy required for a reaction to move forward through several mechanisms:', 'fc64a696-874c-4f51-9e7e-6ed6c917d9b4': 'The kinetics of enzyme-catalyzed reactions is mainly determined by the properties of the catalyst. Like all catalysts, the enzyme [E]\xa0creates a new reaction pathway. Initially, the substrate\xa0[S]\xa0is bound to the free enzyme [ES] (figure 1.3).', '7a3d5064-3a17-423e-9b8c-b79ccc4c312b': 'The rate of this enzyme reaction can be described by the Michaelis–Menten equation, which relates the the initial velocity (vi) to the concentration of substrate [S] and the two parameters Km and Vmax. The Vmax is defined as the maximal velocity that can be achieved at an infinite substrate concentration, while the Km is defined as the substrate concentration needed to reach 1/2 Vmax. The Michaelis constant (Km) characterizes the affinity of the enzyme for a substrate. A high affinity of the enzyme for a substrate therefore leads to a low Km value, and vice versa (figure 1.4).', '6285275b-cc7f-4a99-bd01-83bda78e0599': 'The Michaelis‒Menten model contains simplifying assumptions (substrate binding is in equilibrium, formation of [P] is irreversible, [E] and [ES] are the only enzyme forms).', '94624dd8-fa14-4520-8520-4e57fa1a595f': 'Since vi approaches Vmax asymptotically, it is difficult to read off reliable values for Vmax or Km from diagrams plotting v against [S] (figure 1.4). To alleviate this issue, the Michaelis‒Menten equation can be arranged in such a way that the measured points lie on a straight line. In the Lineweaver‒Burk plot, 1/v is plotted against 1/[S]. The intersections of the line of best fit with the axes then produce 1/Vmax and −1/Km (figure 1.5).'}"
Figure 1.2,cell_bio/images/Figure 1.2.jpg,Figure 1.2: Chart of amino acids.,Amino acids can be grouped largely by the functionality of their R-group (figure 1.2).,"{'2b57c575-c182-45ac-8825-0adb3ee5bfde': 'Table 2.3 adapted from Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017.', 'a1b327f8-105f-4455-970f-d5dc431708e5': 'Amino acids can be grouped largely by the functionality of their R-group (figure 1.2).', '27099d91-541a-4f2d-8c75-4d2e09c8c189': 'Although it is not essential to memorize the structures of the amino acids, a strong understanding of their general characteristics will be very helpful.', 'da24e3df-cc71-4f69-bb99-2a6f76add162': 'Amino acids with uncharged polar R-groups may participate in hydrogen bonding and undergo modifications such as phosphorylation. Tyrosine, serine, and threonine\xa0all have a hydroxyl group\xa0within the R-group, and they can also be readily modified by kinase-mediated phosphorylation.', '5ab9aa34-36fb-487e-8f7a-3e9dab933477': 'Some amino acids are charged at a physiological pH and can be acidic or basic. These side chains may donate or accept protons, respectively, and the most notable charged amino acid is histidine, which can function as a buffer at a physiological pH.', '3067974d-a013-43af-804d-759c9295e62c': '1.1 References and resources', '9bbc330e-7628-4a8a-bea3-1277e24382d9': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 1: Amino Acids, Chapter 2: Protein Structure.', '71e8030c-0f45-4b0d-81e8-5f3946e34f17': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 6: Amino Acids in Proteins, Chapter 8: Enzymes as Catalysts, Chapter 9: Regulation of Enzymes.', '8cda99ef-1df2-4d64-b8aa-1bd12ce5ebb6': '1.2 Enzyme Kinetics', '22762992-8159-4f33-a756-379751eb176b': 'Many translated proteins are also enzymes with\xa0a specific metabolic function within the cell. Enzymes help reduce the amount of transition state energy required for a reaction to move forward through several mechanisms:', 'fc64a696-874c-4f51-9e7e-6ed6c917d9b4': 'The kinetics of enzyme-catalyzed reactions is mainly determined by the properties of the catalyst. Like all catalysts, the enzyme [E]\xa0creates a new reaction pathway. Initially, the substrate\xa0[S]\xa0is bound to the free enzyme [ES] (figure 1.3).', '7a3d5064-3a17-423e-9b8c-b79ccc4c312b': 'The rate of this enzyme reaction can be described by the Michaelis–Menten equation, which relates the the initial velocity (vi) to the concentration of substrate [S] and the two parameters Km and Vmax. The Vmax is defined as the maximal velocity that can be achieved at an infinite substrate concentration, while the Km is defined as the substrate concentration needed to reach 1/2 Vmax. The Michaelis constant (Km) characterizes the affinity of the enzyme for a substrate. A high affinity of the enzyme for a substrate therefore leads to a low Km value, and vice versa (figure 1.4).', '6285275b-cc7f-4a99-bd01-83bda78e0599': 'The Michaelis‒Menten model contains simplifying assumptions (substrate binding is in equilibrium, formation of [P] is irreversible, [E] and [ES] are the only enzyme forms).', '94624dd8-fa14-4520-8520-4e57fa1a595f': 'Since vi approaches Vmax asymptotically, it is difficult to read off reliable values for Vmax or Km from diagrams plotting v against [S] (figure 1.4). To alleviate this issue, the Michaelis‒Menten equation can be arranged in such a way that the measured points lie on a straight line. In the Lineweaver‒Burk plot, 1/v is plotted against 1/[S]. The intersections of the line of best fit with the axes then produce 1/Vmax and −1/Km (figure 1.5).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.3,cell_bio/images/Figure 1.3.jpg,Figure 1.3: Basics of enzyme kinetics.,"The kinetics of enzyme-catalyzed reactions is mainly determined by the properties of the catalyst. Like all catalysts, the enzyme [E] creates a new reaction pathway. Initially, the substrate [S] is bound to the free enzyme [ES] (figure 1.3).","{'da24e3df-cc71-4f69-bb99-2a6f76add162': 'Amino acids with uncharged polar R-groups may participate in hydrogen bonding and undergo modifications such as phosphorylation. Tyrosine, serine, and threonine\xa0all have a hydroxyl group\xa0within the R-group, and they can also be readily modified by kinase-mediated phosphorylation.', '5ab9aa34-36fb-487e-8f7a-3e9dab933477': 'Some amino acids are charged at a physiological pH and can be acidic or basic. These side chains may donate or accept protons, respectively, and the most notable charged amino acid is histidine, which can function as a buffer at a physiological pH.', '3067974d-a013-43af-804d-759c9295e62c': '1.1 References and resources', '9bbc330e-7628-4a8a-bea3-1277e24382d9': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 1: Amino Acids, Chapter 2: Protein Structure.', '71e8030c-0f45-4b0d-81e8-5f3946e34f17': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 6: Amino Acids in Proteins, Chapter 8: Enzymes as Catalysts, Chapter 9: Regulation of Enzymes.', '8cda99ef-1df2-4d64-b8aa-1bd12ce5ebb6': '1.2 Enzyme Kinetics', '22762992-8159-4f33-a756-379751eb176b': 'Many translated proteins are also enzymes with\xa0a specific metabolic function within the cell. Enzymes help reduce the amount of transition state energy required for a reaction to move forward through several mechanisms:', 'fc64a696-874c-4f51-9e7e-6ed6c917d9b4': 'The kinetics of enzyme-catalyzed reactions is mainly determined by the properties of the catalyst. Like all catalysts, the enzyme [E]\xa0creates a new reaction pathway. Initially, the substrate\xa0[S]\xa0is bound to the free enzyme [ES] (figure 1.3).', '7a3d5064-3a17-423e-9b8c-b79ccc4c312b': 'The rate of this enzyme reaction can be described by the Michaelis–Menten equation, which relates the the initial velocity (vi) to the concentration of substrate [S] and the two parameters Km and Vmax. The Vmax is defined as the maximal velocity that can be achieved at an infinite substrate concentration, while the Km is defined as the substrate concentration needed to reach 1/2 Vmax. The Michaelis constant (Km) characterizes the affinity of the enzyme for a substrate. A high affinity of the enzyme for a substrate therefore leads to a low Km value, and vice versa (figure 1.4).', '6285275b-cc7f-4a99-bd01-83bda78e0599': 'The Michaelis‒Menten model contains simplifying assumptions (substrate binding is in equilibrium, formation of [P] is irreversible, [E] and [ES] are the only enzyme forms).', '94624dd8-fa14-4520-8520-4e57fa1a595f': 'Since vi approaches Vmax asymptotically, it is difficult to read off reliable values for Vmax or Km from diagrams plotting v against [S] (figure 1.4). To alleviate this issue, the Michaelis‒Menten equation can be arranged in such a way that the measured points lie on a straight line. In the Lineweaver‒Burk plot, 1/v is plotted against 1/[S]. The intersections of the line of best fit with the axes then produce 1/Vmax and −1/Km (figure 1.5).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.4,cell_bio/images/Figure 1.4.jpg,Figure 1.4: Graphical representation of the Michaelis–Menten equation.,"The rate of this enzyme reaction can be described by the Michaelis–Menten equation, which relates the the initial velocity (vi) to the concentration of substrate [S] and the two parameters Km and Vmax. The Vmax is defined as the maximal velocity that can be achieved at an infinite substrate concentration, while the Km is defined as the substrate concentration needed to reach 1/2 Vmax. The Michaelis constant (Km) characterizes the affinity of the enzyme for a substrate. A high affinity of the enzyme for a substrate therefore leads to a low Km value, and vice versa (figure 1.4).","{'da24e3df-cc71-4f69-bb99-2a6f76add162': 'Amino acids with uncharged polar R-groups may participate in hydrogen bonding and undergo modifications such as phosphorylation. Tyrosine, serine, and threonine\xa0all have a hydroxyl group\xa0within the R-group, and they can also be readily modified by kinase-mediated phosphorylation.', '5ab9aa34-36fb-487e-8f7a-3e9dab933477': 'Some amino acids are charged at a physiological pH and can be acidic or basic. These side chains may donate or accept protons, respectively, and the most notable charged amino acid is histidine, which can function as a buffer at a physiological pH.', '3067974d-a013-43af-804d-759c9295e62c': '1.1 References and resources', '9bbc330e-7628-4a8a-bea3-1277e24382d9': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 1: Amino Acids, Chapter 2: Protein Structure.', '71e8030c-0f45-4b0d-81e8-5f3946e34f17': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 6: Amino Acids in Proteins, Chapter 8: Enzymes as Catalysts, Chapter 9: Regulation of Enzymes.', '8cda99ef-1df2-4d64-b8aa-1bd12ce5ebb6': '1.2 Enzyme Kinetics', '22762992-8159-4f33-a756-379751eb176b': 'Many translated proteins are also enzymes with\xa0a specific metabolic function within the cell. Enzymes help reduce the amount of transition state energy required for a reaction to move forward through several mechanisms:', 'fc64a696-874c-4f51-9e7e-6ed6c917d9b4': 'The kinetics of enzyme-catalyzed reactions is mainly determined by the properties of the catalyst. Like all catalysts, the enzyme [E]\xa0creates a new reaction pathway. Initially, the substrate\xa0[S]\xa0is bound to the free enzyme [ES] (figure 1.3).', '7a3d5064-3a17-423e-9b8c-b79ccc4c312b': 'The rate of this enzyme reaction can be described by the Michaelis–Menten equation, which relates the the initial velocity (vi) to the concentration of substrate [S] and the two parameters Km and Vmax. The Vmax is defined as the maximal velocity that can be achieved at an infinite substrate concentration, while the Km is defined as the substrate concentration needed to reach 1/2 Vmax. The Michaelis constant (Km) characterizes the affinity of the enzyme for a substrate. A high affinity of the enzyme for a substrate therefore leads to a low Km value, and vice versa (figure 1.4).', '6285275b-cc7f-4a99-bd01-83bda78e0599': 'The Michaelis‒Menten model contains simplifying assumptions (substrate binding is in equilibrium, formation of [P] is irreversible, [E] and [ES] are the only enzyme forms).', '94624dd8-fa14-4520-8520-4e57fa1a595f': 'Since vi approaches Vmax asymptotically, it is difficult to read off reliable values for Vmax or Km from diagrams plotting v against [S] (figure 1.4). To alleviate this issue, the Michaelis‒Menten equation can be arranged in such a way that the measured points lie on a straight line. In the Lineweaver‒Burk plot, 1/v is plotted against 1/[S]. The intersections of the line of best fit with the axes then produce 1/Vmax and −1/Km (figure 1.5).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.6,cell_bio/images/Figure 1.6.jpg,Figure 1.6: Competitive vs. noncompetitive inhibition.,"Competitive inhibitors bind the enzyme at the active site and compete with the substrate for binding. Many function as substrate analogs. In the presence of the inhibitor, a higher substrate concentration is therefore needed to achieve a half-maximum rate; the Michaelis constant Km increases. When substrate concentrations are elevated, this will ultimately displace the inhibitor, and Vmax will be reached. The maximum rate, Vmax, is therefore not influenced by competitive inhibitors. In this case, there is no change on Vmax as competition can be overcome by increasing the concentration of substrate, but there is an increase in the apparent Km, as a greater substrate concentration is needed to reach Vmax (figure 1.6(a)).","{'317eef11-b243-409d-b803-09d325fcf076': 'Enzymes can be inhibited or activated by interference from other compounds. These will influence the reaction by changing the Km or Vmax\xa0of the reaction. Most enzyme inhibitors act reversibly and do not cause permanent changes in the enzyme. However, there are also irreversible inhibitors that modify the target enzyme covalently and permanently. These are termed suicide inhibitors.', '6bc8407e-1cd5-43e6-9062-b1c9d6228070': 'Inhibitors can be categorized as competitive or noncompetitive, and this can be determined by comparing the kinetics of the normal versus\xa0inhibited reactions.', 'c7133a99-dec0-452c-b2dc-6761ba41d6b7': 'Competitive inhibitors bind the enzyme at the active site and compete with the substrate for binding. Many function as substrate analogs. In the presence of the inhibitor, a higher substrate concentration is therefore needed to achieve a half-maximum rate; the Michaelis constant Km increases. When substrate concentrations are elevated, this will ultimately displace the inhibitor, and Vmax will be reached. The maximum rate, Vmax, is therefore not influenced by competitive inhibitors. In this case, there is no change on Vmax\xa0as competition can be overcome by\xa0increasing the concentration of substrate, but there is an increase in the apparent Km, as a greater substrate concentration is needed to reach Vmax (figure 1.6(a)).', '167e2378-7373-44d7-a45a-5b93386604c8': 'In contrast, noncompetitive inhibitors bind the enzyme on a site alternative to the substrate binding site, and therefore its effects cannot be overcome by increasing the substrate. In this case, Km\xa0remains unchanged, but kcat (the rate of product formation), and thus Vmax, decreases. Irreversible inhibitors usually result in a noncompetitive type of inhibition because the concentration of active enzyme [E] decreases (figure 1.6(b)).', 'f47737b8-f52a-4656-a8d8-d4c7f1d1a83f': 'The action of inhibitors can be illustrated clearly in the Lineweaver‒Burk plot. In this type of plot, the intercept of the approximation lines with the y-axis corresponds to 1/Vmax, while the x-axis intercept gives the value of −1/Km. This is why the straight lines obtained in the absence (blue) and presence of a competitive inhibitor (A, red) intersect on the y-axis (1/ Vmax), unchanged), while noncompetitive inhibitors (B, red) result in a straight line with a higher y-intercept but unchanged x-intercept (1/Vmax) increased, Km) unchanged) (figure 1.6).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.7,cell_bio/images/Figure 1.7.jpg,Figure 1.7(a): Allosteric enzyme regulation.,"The Michaelis‒Menten model of enzyme catalysis assumes that the enzymeʼs spatial structure does not alter with substrate binding. However, many enzymes are present in various conformations, which have different catalytic properties. Allosteric enzymes can be recognized by their S-shaped (sigmoidal) saturation curves, which cannot be described using the Michaelis‒Menten equation. In allosteric enzymes, the binding efficiency initially rises with increasing [S], because the free enzyme is present in a low-affinity conformation, which is gradually converted into a higher-affinity form. It is only at high [S] values that a lack of free binding sites becomes noticeable and the binding efficiency decreases again. The affinity of allosteric enzymes is therefore not constant, but depends on the type and concentration of the ligand. Inhibitors and activators (effectors) influence the activity of allosteric enzymes by stabilizing certain conformations. These effects play an important part in regulating metabolism (figure 1.7).","{'c7afc137-694b-48fa-bf4a-6672386ff072': 'The Michaelis‒Menten model of enzyme catalysis assumes that the enzymeʼs spatial structure does not alter with substrate binding. However, many enzymes are present in various conformations, which have different catalytic properties. Allosteric enzymes can be recognized by their S-shaped (sigmoidal) saturation curves, which cannot be described using the Michaelis‒Menten equation. In allosteric enzymes, the binding efficiency initially rises with increasing [S], because the free enzyme is present in a low-affinity conformation, which is gradually converted into a higher-affinity form. It is only at high [S] values that a lack of free binding sites becomes noticeable and the binding efficiency decreases again. The affinity of allosteric enzymes is therefore not constant, but depends on the type and concentration of the ligand. Inhibitors and activators (effectors) influence the activity of allosteric enzymes by stabilizing certain conformations. These effects play an important part in regulating metabolism (figure 1.7).', 'a0f3c348-ebc3-4b53-86a1-40420b507ddc': 'Similar to noncompetitive inhibitors, allosteric effectors will bind sites alternative to the active site. Allosteric activators typically stabilize the relaxed conformation of an enzyme (R), and increase the rate of substrate binding of the subsequent subunits. This is called cooperativity. In contrast, allosteric inhibitors will stabilize the tense (T) conformation of a protein and will increase substrate off (release) rate. The best example of this is with oxygen binding to hemoglobin, which has a quaternary structure with four binding sites for oxygen.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.7,cell_bio/images/Figure 1.7.jpg,Figure 1.7(b): Allosteric enzyme regulation.,"The Michaelis‒Menten model of enzyme catalysis assumes that the enzymeʼs spatial structure does not alter with substrate binding. However, many enzymes are present in various conformations, which have different catalytic properties. Allosteric enzymes can be recognized by their S-shaped (sigmoidal) saturation curves, which cannot be described using the Michaelis‒Menten equation. In allosteric enzymes, the binding efficiency initially rises with increasing [S], because the free enzyme is present in a low-affinity conformation, which is gradually converted into a higher-affinity form. It is only at high [S] values that a lack of free binding sites becomes noticeable and the binding efficiency decreases again. The affinity of allosteric enzymes is therefore not constant, but depends on the type and concentration of the ligand. Inhibitors and activators (effectors) influence the activity of allosteric enzymes by stabilizing certain conformations. These effects play an important part in regulating metabolism (figure 1.7).","{'c7afc137-694b-48fa-bf4a-6672386ff072': 'The Michaelis‒Menten model of enzyme catalysis assumes that the enzymeʼs spatial structure does not alter with substrate binding. However, many enzymes are present in various conformations, which have different catalytic properties. Allosteric enzymes can be recognized by their S-shaped (sigmoidal) saturation curves, which cannot be described using the Michaelis‒Menten equation. In allosteric enzymes, the binding efficiency initially rises with increasing [S], because the free enzyme is present in a low-affinity conformation, which is gradually converted into a higher-affinity form. It is only at high [S] values that a lack of free binding sites becomes noticeable and the binding efficiency decreases again. The affinity of allosteric enzymes is therefore not constant, but depends on the type and concentration of the ligand. Inhibitors and activators (effectors) influence the activity of allosteric enzymes by stabilizing certain conformations. These effects play an important part in regulating metabolism (figure 1.7).', 'a0f3c348-ebc3-4b53-86a1-40420b507ddc': 'Similar to noncompetitive inhibitors, allosteric effectors will bind sites alternative to the active site. Allosteric activators typically stabilize the relaxed conformation of an enzyme (R), and increase the rate of substrate binding of the subsequent subunits. This is called cooperativity. In contrast, allosteric inhibitors will stabilize the tense (T) conformation of a protein and will increase substrate off (release) rate. The best example of this is with oxygen binding to hemoglobin, which has a quaternary structure with four binding sites for oxygen.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.3,cell_bio/images/Figure 1.3.jpg,Figure 1.3: Basics of enzyme kinetics.,"The kinetics of enzyme-catalyzed reactions is mainly determined by the properties of the catalyst. Like all catalysts, the enzyme [E] creates a new reaction pathway. Initially, the substrate [S] is bound to the free enzyme [ES] (figure 1.3).","{'da24e3df-cc71-4f69-bb99-2a6f76add162': 'Amino acids with uncharged polar R-groups may participate in hydrogen bonding and undergo modifications such as phosphorylation. Tyrosine, serine, and threonine\xa0all have a hydroxyl group\xa0within the R-group, and they can also be readily modified by kinase-mediated phosphorylation.', '5ab9aa34-36fb-487e-8f7a-3e9dab933477': 'Some amino acids are charged at a physiological pH and can be acidic or basic. These side chains may donate or accept protons, respectively, and the most notable charged amino acid is histidine, which can function as a buffer at a physiological pH.', '3067974d-a013-43af-804d-759c9295e62c': '1.1 References and resources', '9bbc330e-7628-4a8a-bea3-1277e24382d9': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 1: Amino Acids, Chapter 2: Protein Structure.', '71e8030c-0f45-4b0d-81e8-5f3946e34f17': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 6: Amino Acids in Proteins, Chapter 8: Enzymes as Catalysts, Chapter 9: Regulation of Enzymes.', '8cda99ef-1df2-4d64-b8aa-1bd12ce5ebb6': '1.2 Enzyme Kinetics', '22762992-8159-4f33-a756-379751eb176b': 'Many translated proteins are also enzymes with\xa0a specific metabolic function within the cell. Enzymes help reduce the amount of transition state energy required for a reaction to move forward through several mechanisms:', 'fc64a696-874c-4f51-9e7e-6ed6c917d9b4': 'The kinetics of enzyme-catalyzed reactions is mainly determined by the properties of the catalyst. Like all catalysts, the enzyme [E]\xa0creates a new reaction pathway. Initially, the substrate\xa0[S]\xa0is bound to the free enzyme [ES] (figure 1.3).', '7a3d5064-3a17-423e-9b8c-b79ccc4c312b': 'The rate of this enzyme reaction can be described by the Michaelis–Menten equation, which relates the the initial velocity (vi) to the concentration of substrate [S] and the two parameters Km and Vmax. The Vmax is defined as the maximal velocity that can be achieved at an infinite substrate concentration, while the Km is defined as the substrate concentration needed to reach 1/2 Vmax. The Michaelis constant (Km) characterizes the affinity of the enzyme for a substrate. A high affinity of the enzyme for a substrate therefore leads to a low Km value, and vice versa (figure 1.4).', '6285275b-cc7f-4a99-bd01-83bda78e0599': 'The Michaelis‒Menten model contains simplifying assumptions (substrate binding is in equilibrium, formation of [P] is irreversible, [E] and [ES] are the only enzyme forms).', '94624dd8-fa14-4520-8520-4e57fa1a595f': 'Since vi approaches Vmax asymptotically, it is difficult to read off reliable values for Vmax or Km from diagrams plotting v against [S] (figure 1.4). To alleviate this issue, the Michaelis‒Menten equation can be arranged in such a way that the measured points lie on a straight line. In the Lineweaver‒Burk plot, 1/v is plotted against 1/[S]. The intersections of the line of best fit with the axes then produce 1/Vmax and −1/Km (figure 1.5).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.4,cell_bio/images/Figure 1.4.jpg,Figure 1.4: Graphical representation of the Michaelis–Menten equation.,"The rate of this enzyme reaction can be described by the Michaelis–Menten equation, which relates the the initial velocity (vi) to the concentration of substrate [S] and the two parameters Km and Vmax. The Vmax is defined as the maximal velocity that can be achieved at an infinite substrate concentration, while the Km is defined as the substrate concentration needed to reach 1/2 Vmax. The Michaelis constant (Km) characterizes the affinity of the enzyme for a substrate. A high affinity of the enzyme for a substrate therefore leads to a low Km value, and vice versa (figure 1.4).","{'da24e3df-cc71-4f69-bb99-2a6f76add162': 'Amino acids with uncharged polar R-groups may participate in hydrogen bonding and undergo modifications such as phosphorylation. Tyrosine, serine, and threonine\xa0all have a hydroxyl group\xa0within the R-group, and they can also be readily modified by kinase-mediated phosphorylation.', '5ab9aa34-36fb-487e-8f7a-3e9dab933477': 'Some amino acids are charged at a physiological pH and can be acidic or basic. These side chains may donate or accept protons, respectively, and the most notable charged amino acid is histidine, which can function as a buffer at a physiological pH.', '3067974d-a013-43af-804d-759c9295e62c': '1.1 References and resources', '9bbc330e-7628-4a8a-bea3-1277e24382d9': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 1: Amino Acids, Chapter 2: Protein Structure.', '71e8030c-0f45-4b0d-81e8-5f3946e34f17': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 6: Amino Acids in Proteins, Chapter 8: Enzymes as Catalysts, Chapter 9: Regulation of Enzymes.', '8cda99ef-1df2-4d64-b8aa-1bd12ce5ebb6': '1.2 Enzyme Kinetics', '22762992-8159-4f33-a756-379751eb176b': 'Many translated proteins are also enzymes with\xa0a specific metabolic function within the cell. Enzymes help reduce the amount of transition state energy required for a reaction to move forward through several mechanisms:', 'fc64a696-874c-4f51-9e7e-6ed6c917d9b4': 'The kinetics of enzyme-catalyzed reactions is mainly determined by the properties of the catalyst. Like all catalysts, the enzyme [E]\xa0creates a new reaction pathway. Initially, the substrate\xa0[S]\xa0is bound to the free enzyme [ES] (figure 1.3).', '7a3d5064-3a17-423e-9b8c-b79ccc4c312b': 'The rate of this enzyme reaction can be described by the Michaelis–Menten equation, which relates the the initial velocity (vi) to the concentration of substrate [S] and the two parameters Km and Vmax. The Vmax is defined as the maximal velocity that can be achieved at an infinite substrate concentration, while the Km is defined as the substrate concentration needed to reach 1/2 Vmax. The Michaelis constant (Km) characterizes the affinity of the enzyme for a substrate. A high affinity of the enzyme for a substrate therefore leads to a low Km value, and vice versa (figure 1.4).', '6285275b-cc7f-4a99-bd01-83bda78e0599': 'The Michaelis‒Menten model contains simplifying assumptions (substrate binding is in equilibrium, formation of [P] is irreversible, [E] and [ES] are the only enzyme forms).', '94624dd8-fa14-4520-8520-4e57fa1a595f': 'Since vi approaches Vmax asymptotically, it is difficult to read off reliable values for Vmax or Km from diagrams plotting v against [S] (figure 1.4). To alleviate this issue, the Michaelis‒Menten equation can be arranged in such a way that the measured points lie on a straight line. In the Lineweaver‒Burk plot, 1/v is plotted against 1/[S]. The intersections of the line of best fit with the axes then produce 1/Vmax and −1/Km (figure 1.5).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.5,cell_bio/images/Figure 1.5.jpg,Figure 1.5: Lineweaver–Burk plot to illustrate Km and Vmax.,"Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.","{'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.6,cell_bio/images/Figure 1.6.jpg,Figure 1.6: Competitive vs. noncompetitive inhibition.,"Competitive inhibitors bind the enzyme at the active site and compete with the substrate for binding. Many function as substrate analogs. In the presence of the inhibitor, a higher substrate concentration is therefore needed to achieve a half-maximum rate; the Michaelis constant Km increases. When substrate concentrations are elevated, this will ultimately displace the inhibitor, and Vmax will be reached. The maximum rate, Vmax, is therefore not influenced by competitive inhibitors. In this case, there is no change on Vmax as competition can be overcome by increasing the concentration of substrate, but there is an increase in the apparent Km, as a greater substrate concentration is needed to reach Vmax (figure 1.6(a)).","{'317eef11-b243-409d-b803-09d325fcf076': 'Enzymes can be inhibited or activated by interference from other compounds. These will influence the reaction by changing the Km or Vmax\xa0of the reaction. Most enzyme inhibitors act reversibly and do not cause permanent changes in the enzyme. However, there are also irreversible inhibitors that modify the target enzyme covalently and permanently. These are termed suicide inhibitors.', '6bc8407e-1cd5-43e6-9062-b1c9d6228070': 'Inhibitors can be categorized as competitive or noncompetitive, and this can be determined by comparing the kinetics of the normal versus\xa0inhibited reactions.', 'c7133a99-dec0-452c-b2dc-6761ba41d6b7': 'Competitive inhibitors bind the enzyme at the active site and compete with the substrate for binding. Many function as substrate analogs. In the presence of the inhibitor, a higher substrate concentration is therefore needed to achieve a half-maximum rate; the Michaelis constant Km increases. When substrate concentrations are elevated, this will ultimately displace the inhibitor, and Vmax will be reached. The maximum rate, Vmax, is therefore not influenced by competitive inhibitors. In this case, there is no change on Vmax\xa0as competition can be overcome by\xa0increasing the concentration of substrate, but there is an increase in the apparent Km, as a greater substrate concentration is needed to reach Vmax (figure 1.6(a)).', '167e2378-7373-44d7-a45a-5b93386604c8': 'In contrast, noncompetitive inhibitors bind the enzyme on a site alternative to the substrate binding site, and therefore its effects cannot be overcome by increasing the substrate. In this case, Km\xa0remains unchanged, but kcat (the rate of product formation), and thus Vmax, decreases. Irreversible inhibitors usually result in a noncompetitive type of inhibition because the concentration of active enzyme [E] decreases (figure 1.6(b)).', 'f47737b8-f52a-4656-a8d8-d4c7f1d1a83f': 'The action of inhibitors can be illustrated clearly in the Lineweaver‒Burk plot. In this type of plot, the intercept of the approximation lines with the y-axis corresponds to 1/Vmax, while the x-axis intercept gives the value of −1/Km. This is why the straight lines obtained in the absence (blue) and presence of a competitive inhibitor (A, red) intersect on the y-axis (1/ Vmax), unchanged), while noncompetitive inhibitors (B, red) result in a straight line with a higher y-intercept but unchanged x-intercept (1/Vmax) increased, Km) unchanged) (figure 1.6).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.7,cell_bio/images/Figure 1.7.jpg,Figure 1.7(a): Allosteric enzyme regulation.,"The Michaelis‒Menten model of enzyme catalysis assumes that the enzymeʼs spatial structure does not alter with substrate binding. However, many enzymes are present in various conformations, which have different catalytic properties. Allosteric enzymes can be recognized by their S-shaped (sigmoidal) saturation curves, which cannot be described using the Michaelis‒Menten equation. In allosteric enzymes, the binding efficiency initially rises with increasing [S], because the free enzyme is present in a low-affinity conformation, which is gradually converted into a higher-affinity form. It is only at high [S] values that a lack of free binding sites becomes noticeable and the binding efficiency decreases again. The affinity of allosteric enzymes is therefore not constant, but depends on the type and concentration of the ligand. Inhibitors and activators (effectors) influence the activity of allosteric enzymes by stabilizing certain conformations. These effects play an important part in regulating metabolism (figure 1.7).","{'c7afc137-694b-48fa-bf4a-6672386ff072': 'The Michaelis‒Menten model of enzyme catalysis assumes that the enzymeʼs spatial structure does not alter with substrate binding. However, many enzymes are present in various conformations, which have different catalytic properties. Allosteric enzymes can be recognized by their S-shaped (sigmoidal) saturation curves, which cannot be described using the Michaelis‒Menten equation. In allosteric enzymes, the binding efficiency initially rises with increasing [S], because the free enzyme is present in a low-affinity conformation, which is gradually converted into a higher-affinity form. It is only at high [S] values that a lack of free binding sites becomes noticeable and the binding efficiency decreases again. The affinity of allosteric enzymes is therefore not constant, but depends on the type and concentration of the ligand. Inhibitors and activators (effectors) influence the activity of allosteric enzymes by stabilizing certain conformations. These effects play an important part in regulating metabolism (figure 1.7).', 'a0f3c348-ebc3-4b53-86a1-40420b507ddc': 'Similar to noncompetitive inhibitors, allosteric effectors will bind sites alternative to the active site. Allosteric activators typically stabilize the relaxed conformation of an enzyme (R), and increase the rate of substrate binding of the subsequent subunits. This is called cooperativity. In contrast, allosteric inhibitors will stabilize the tense (T) conformation of a protein and will increase substrate off (release) rate. The best example of this is with oxygen binding to hemoglobin, which has a quaternary structure with four binding sites for oxygen.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.7,cell_bio/images/Figure 1.7.jpg,Figure 1.7(b): Allosteric enzyme regulation.,"The Michaelis‒Menten model of enzyme catalysis assumes that the enzymeʼs spatial structure does not alter with substrate binding. However, many enzymes are present in various conformations, which have different catalytic properties. Allosteric enzymes can be recognized by their S-shaped (sigmoidal) saturation curves, which cannot be described using the Michaelis‒Menten equation. In allosteric enzymes, the binding efficiency initially rises with increasing [S], because the free enzyme is present in a low-affinity conformation, which is gradually converted into a higher-affinity form. It is only at high [S] values that a lack of free binding sites becomes noticeable and the binding efficiency decreases again. The affinity of allosteric enzymes is therefore not constant, but depends on the type and concentration of the ligand. Inhibitors and activators (effectors) influence the activity of allosteric enzymes by stabilizing certain conformations. These effects play an important part in regulating metabolism (figure 1.7).","{'c7afc137-694b-48fa-bf4a-6672386ff072': 'The Michaelis‒Menten model of enzyme catalysis assumes that the enzymeʼs spatial structure does not alter with substrate binding. However, many enzymes are present in various conformations, which have different catalytic properties. Allosteric enzymes can be recognized by their S-shaped (sigmoidal) saturation curves, which cannot be described using the Michaelis‒Menten equation. In allosteric enzymes, the binding efficiency initially rises with increasing [S], because the free enzyme is present in a low-affinity conformation, which is gradually converted into a higher-affinity form. It is only at high [S] values that a lack of free binding sites becomes noticeable and the binding efficiency decreases again. The affinity of allosteric enzymes is therefore not constant, but depends on the type and concentration of the ligand. Inhibitors and activators (effectors) influence the activity of allosteric enzymes by stabilizing certain conformations. These effects play an important part in regulating metabolism (figure 1.7).', 'a0f3c348-ebc3-4b53-86a1-40420b507ddc': 'Similar to noncompetitive inhibitors, allosteric effectors will bind sites alternative to the active site. Allosteric activators typically stabilize the relaxed conformation of an enzyme (R), and increase the rate of substrate binding of the subsequent subunits. This is called cooperativity. In contrast, allosteric inhibitors will stabilize the tense (T) conformation of a protein and will increase substrate off (release) rate. The best example of this is with oxygen binding to hemoglobin, which has a quaternary structure with four binding sites for oxygen.', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"
Figure 1.2,cell_bio/images/Figure 1.2.jpg,Figure 1.2: Chart of amino acids.,Amino acids can be grouped largely by the functionality of their R-group (figure 1.2).,"{'2b57c575-c182-45ac-8825-0adb3ee5bfde': 'Table 2.3 adapted from Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017.', 'a1b327f8-105f-4455-970f-d5dc431708e5': 'Amino acids can be grouped largely by the functionality of their R-group (figure 1.2).', '27099d91-541a-4f2d-8c75-4d2e09c8c189': 'Although it is not essential to memorize the structures of the amino acids, a strong understanding of their general characteristics will be very helpful.', 'da24e3df-cc71-4f69-bb99-2a6f76add162': 'Amino acids with uncharged polar R-groups may participate in hydrogen bonding and undergo modifications such as phosphorylation. Tyrosine, serine, and threonine\xa0all have a hydroxyl group\xa0within the R-group, and they can also be readily modified by kinase-mediated phosphorylation.', '5ab9aa34-36fb-487e-8f7a-3e9dab933477': 'Some amino acids are charged at a physiological pH and can be acidic or basic. These side chains may donate or accept protons, respectively, and the most notable charged amino acid is histidine, which can function as a buffer at a physiological pH.', '3067974d-a013-43af-804d-759c9295e62c': '1.1 References and resources', '9bbc330e-7628-4a8a-bea3-1277e24382d9': 'Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 1: Amino Acids, Chapter 2: Protein Structure.', '71e8030c-0f45-4b0d-81e8-5f3946e34f17': 'Lieberman, M., and A. Peet, eds. Marks’ Basic Medical Biochemistry: A Clinical Approach, 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2018, Chapter 6: Amino Acids in Proteins, Chapter 8: Enzymes as Catalysts, Chapter 9: Regulation of Enzymes.', '8cda99ef-1df2-4d64-b8aa-1bd12ce5ebb6': '1.2 Enzyme Kinetics', '22762992-8159-4f33-a756-379751eb176b': 'Many translated proteins are also enzymes with\xa0a specific metabolic function within the cell. Enzymes help reduce the amount of transition state energy required for a reaction to move forward through several mechanisms:', 'fc64a696-874c-4f51-9e7e-6ed6c917d9b4': 'The kinetics of enzyme-catalyzed reactions is mainly determined by the properties of the catalyst. Like all catalysts, the enzyme [E]\xa0creates a new reaction pathway. Initially, the substrate\xa0[S]\xa0is bound to the free enzyme [ES] (figure 1.3).', '7a3d5064-3a17-423e-9b8c-b79ccc4c312b': 'The rate of this enzyme reaction can be described by the Michaelis–Menten equation, which relates the the initial velocity (vi) to the concentration of substrate [S] and the two parameters Km and Vmax. The Vmax is defined as the maximal velocity that can be achieved at an infinite substrate concentration, while the Km is defined as the substrate concentration needed to reach 1/2 Vmax. The Michaelis constant (Km) characterizes the affinity of the enzyme for a substrate. A high affinity of the enzyme for a substrate therefore leads to a low Km value, and vice versa (figure 1.4).', '6285275b-cc7f-4a99-bd01-83bda78e0599': 'The Michaelis‒Menten model contains simplifying assumptions (substrate binding is in equilibrium, formation of [P] is irreversible, [E] and [ES] are the only enzyme forms).', '94624dd8-fa14-4520-8520-4e57fa1a595f': 'Since vi approaches Vmax asymptotically, it is difficult to read off reliable values for Vmax or Km from diagrams plotting v against [S] (figure 1.4). To alleviate this issue, the Michaelis‒Menten equation can be arranged in such a way that the measured points lie on a straight line. In the Lineweaver‒Burk plot, 1/v is plotted against 1/[S]. The intersections of the line of best fit with the axes then produce 1/Vmax and −1/Km (figure 1.5).', 'b6936001-2396-40f5-a803-c4e0c22f779b': 'Lieberman M, Peet A. Figure 16.11 Primary active transport. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 175 Figure 10.10 Active transport by Na+,K+-ATPase. 2017. Added Cell membrane detailed diagram blank by LadyofHats. Public domain. From Wikimedia Commons. Added ion channel by Léa Lortal from the Noun Project.', '18cc6256-46dc-4c76-8eba-9461c14b30da': 'Generally speaking, it uses various communication modalities to sense and respond to neighboring cells and environmental cues, which can be categorized into the following types of communication (figure 15.1):', 'baf260bc-ef35-4eb2-9c96-302ff06b1148': 'Lieberman M, Peet A. Figure 15.8 Summary of the action potential to membrane potential. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 199. Figure 11.11 Signal transduction by tyrosine receptors. 2017.', '3e89a806-2482-4bc6-87bc-615f124ba307': 'Grey, Kindred, Figure 14.5: Trinucleotide repeat expansion characteristic of Huntington’s disease. 2021.', '4c40c5fe-8426-4b90-98ef-202551e09788': '14.3 Linkage Analysis and Genome-Wide Association Studies (GWAS)', 'e5f8b84d-9def-42fb-b50a-88f6d1ffc5f7': 'There is tremendous interest in finding specific genes that predispose individuals to common disease traits, most of which follow complex inheritance patterns rather than Mendelian (single gene) patterns. Physicians will find frequent references in the medical literature related to the search for genes with high predictive value in common disorders.', 'f99fffb5-cb0a-4426-a355-db96f3677516': 'While we know the DNA sequence of the vast majority of the coding regions of the genome, we still do not understand the full function of the majority of genes or how they are involved in human health conditions. There are two major approaches to identifying genetic loci, which contribute to disease presentation: linkage analysis and genome-wide association studies.', '25559ec4-a7fc-462d-80b4-4ad8c36492fc': '12.3 Meiosis', '9a28540c-770e-4d36-8678-b8278223e355': 'The twenty-three\xa0chromosome pairs in humans\xa0accounts for all the genetic information needed to survive. For most of the components within the cell, only an approximation of division is needed during cell replication, however, with respect to division of DNA, this duplication and segregation must be exact. The integrity of the genetic information within the cell is critical for the well-being of the organisms and its offspring, so these processes are clearly controlled.', '6ad6a192-a3c3-4c94-baf1-9e85513f7b41': 'Within the cell cycle, the process of mitosis is largely responsible for this intricate chromosomal division of the somatic (body) cells by which two identical diploid daughter cells are produced through deoxyribonucleic acid (DNA) replication and cytoplasmic division.', 'da75e659-0020-4de3-afe1-eea1197d5a94': 'In contrast, meiosis\xa0is a specialized process of the germline (sperm and eggs) that involves one round of DNA replication followed by two cell divisions to produce four haploid germ cells. Unlike mitosis, the resulting germ cells differ in males and females.', 'b42ff3d7-8c5d-4659-b637-9b2d0f1d2f15': 'Male meiosis results in the production of four equally sized, functional spermatozoa, while female meiosis results in a single large functional ovum and three small nonfunctional polar bodies. Abnormalities in these processes include chromosomal nondisjunction, which results in the loss or gain of one or more chromosomes, and chromosomal breakage due to unrepaired DNA damage, which results in the formation of abnormal chromosomes and an increased risk for neoplasia.', '0aa9b910-1639-4a13-bf0d-ba377672fa43': '5.3 Nitrogen Metabolism and the Urea Cycle', '398e30a1-9d07-425c-92b9-be0f1b0c477e': 'Amino acids play key roles as precursors to nitrogen-containing compounds (such as nucleotides and neurotransmitters), as substrates for protein synthesis, and as an oxidizable substrate for energy production (or storage). Unlike carbohydrate and lipid metabolism, we must be concerned with the fates of both the carbon- and nitrogen-containing moieties when discussing the metabolism of amino acids. In the case of amino acids, nitrogen is released as ammonia (NH3), and at physiological pH the majority of ammonia is present as an ammonium ion (NH4+). (It is important to note that only ammonia can cross cellular membranes.)\xa0The majority of ammonia is incorporated into urea (in the liver) and excreted by the kidney, while the remaining carbon-containing skeleton is oxidized or utilized in other anabolic pathways (i.e., gluconeogenesis).', 'c7066105-ee10-4f3c-8c80-fe6a731096ad': '4.4 Fatty Acid Synthesis', 'ac7c090e-aff8-4808-b9b4-584d5899b86c': 'The synthesis of fatty acids is an anabolic pathway that occurs in the cytosol under fed conditions. As glucose is taken up by the liver and the flux through the TCA cycle increases, excess citrate is removed via the citrate shuttle. Once in the cytosol, citrate is cleaved by citrate lyase back into oxaloacetate (OAA) and acetyl-CoA. The OAA can be reduced to malate by cytosolic malate dehydrogenase and decarboxylated by malic enzyme producing pyruvate and NADPH (figure 4.15).', 'd3bcd72c-ff62-4dab-8c84-b13faa076297': 'The NADPH generated through this process is necessary for fatty acid synthesis. This is one of the primary pathways that\xa0produces NADPH, and the other is the oxidative portion of the pentose pathway.', '38322525-b9c6-4452-9ff8-4fcf60958d18': 'The process of fatty acid synthesis starts with the carboxylation of acetyl-CoA to form malonyl-CoA (figures 4.16 and 4.17). The enzyme involved, acetyl-CoA carboxylase, is the regulatory enzyme for this pathway and requires biotin as a cofactor. After the initial priming of fatty acid synthase with acetyl-CoA, all other carbon units are added to the elongating fatty acid chain in the form of malonyl-CoA. You will see later that this intermediate is also a key inhibitor of β-oxidation.', 'c304cd0e-47af-41c9-81c3-2fc3effd0480': 'The synthesis of fatty acids by fatty acid synthase initially starts with the transfer of an acetyl moiety from acetyl-CoA to the acyl carrier protein within fatty acid synthase. Malonyl-CoA is added to the acetyl group and decarboxylated to form a four-carbon β-keto chain. From here, the fatty acid chain is elongated through a series of dehydration and reduction reactions, which use NADPH as a reducing agent. The final product is palmitate, a C-16 molecule (figure 4.16). Fatty acids are not stored in the liver and must be packaged into VLDL particles for transport to peripheral tissues for storage. To produce VLDL particles, the newly synthesized fatty acids are packaged into triacylglycerols (TAGs). TAG synthesis can take place in both the liver and adipose tissue. Synthesis requires glycerol 3-phosphate, which can be derived from glycolysis or from the phosphorylation of glycerol using glycerol kinase in the liver. Three fatty acyl-CoA groups react with the glycerol 3-phosphate to form a TAG. TAGs, along with cholesterol, are packaged into VLDLs distributed into circulation (section 6.2).', '175d5875-6f06-4038-8540-99d328f4cc0e': 'Ferrier D. Figure 2.3 Mechanism of action of Vitamin A. Adapted under Fair Use from Figure 28.20 Action of the retinoids. Lippincott Illustrated Reviews Biochemistry. 7th Ed. pp388. 2017. Chemical structure by Henry Jakubowski.', '8c5504b4-2266-4922-8ca6-8cb36b4a358d': 'Lieberman M, Peet A. Figure 1.4 Graphical representation of the Michaelis-Menten equation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 152. Figure 9.2 A graph of the Michaelis-Menten equation. 2017.', 'b94332c2-5c5c-4241-8320-167fa2151c12': 'Lieberman M, Peet A. Figure 1.5 Lineweaver-Burk plot to illustrate Km and Vmax. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 153. Figure 9.3 The Lineweaver-Burk transformation for the Michaelis-Menten equation. 2017.', '34677d70-0970-4bc8-be24-8ead6dd4a18b': 'Lieberman M, Peet A. Figure 1.6 Competitive vs. noncompetitive inhibition. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 156. Figure 9.6 Lineweaver-Burk plots of competitive and purenoncompetitive inhibition. 2017.', '686b93bc-5742-447c-9446-3005dead833a': 'Lieberman M, Peet A. Figure 1.7 Allosteric enzyme regulation. Adapted under Fair Use from Marks’ Basic Medical Biochemistry. 5th Ed. pp 157. Figure 9.8 Activators and inhibitors of an allosteric enzyme (simplified model). 2017.'}"