Diseases and medically relevant topics |
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xxiii | |
Abbreviations |
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xxv | |
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Part 1 Basic concepts of life |
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Chapter 1 The basic molecular themes of life |
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3 | (13) |
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All life forms are similar at the molecular level |
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3 | (1) |
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4 | (1) |
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The laws of thermodynamics deal with energy |
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4 | (1) |
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Energy can be transformed from one state to another |
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5 | (1) |
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ATP (adenosine triphosphate) is the universal energy currency in life |
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5 | (1) |
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Types of molecules found in living cells |
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5 | (3) |
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6 | (1) |
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Macromolecules are made by polymerization of smaller units |
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7 | (1) |
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Protein and nucleic acid molecules have information content |
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7 | (1) |
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8 | (1) |
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Catalysis of reactions by enzyme proteins is central to the existence of life |
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8 | (1) |
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What is the function of enzymes? |
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8 | (1) |
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Proteins work by molecular recognition |
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9 | (1) |
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Life is self-assembling due to molecular recognition by proteins |
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9 | (1) |
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Many proteins are molecular machines |
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9 | (1) |
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How can one class of molecule carry out so many tasks? |
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9 | (1) |
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9 | (1) |
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9 | (1) |
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DNA (deoxyribonucleic acid) |
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10 | (2) |
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DNA directs its own replication |
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10 | (1) |
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10 | (2) |
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Organization of the genome |
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12 | (1) |
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12 | (1) |
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13 | (1) |
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13 | (3) |
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13 | (2) |
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15 | (1) |
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15 | (1) |
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Chapter 2 Cells and viruses |
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16 | (11) |
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Cells are the units of all living systems |
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16 | (1) |
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What determines the size of cells? |
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16 | (1) |
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Classification of organisms |
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16 | (7) |
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17 | (1) |
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18 | (3) |
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Basic types of eukaryotic cells |
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21 | (2) |
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23 | (4) |
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25 | (1) |
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26 | (1) |
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26 | (1) |
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Chapter 3 Energy considerations in biochemistry |
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27 | (18) |
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Energy considerations determine whether a chemical reaction is possible in the cell |
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27 | (1) |
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Reversible and irreversible reactions and G values |
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28 | (1) |
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The importance of irreversible reactions in the strategy of metabolism |
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29 | (1) |
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What is the significance of irreversible reactions in a metabolic pathway? |
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29 | (1) |
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How are G values obtained? |
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29 | (1) |
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Standard free energy values and equilibrium constants |
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30 | (1) |
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The release and utilization of free energy from food |
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30 | (1) |
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ATP is the universal energy intermediate in all life |
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31 | (5) |
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What are the structural features of high-energy phosphate compounds? |
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31 | (2) |
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33 | (1) |
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What transports the--- around the cell? |
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33 | (1) |
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How does ATP drive chemical work? |
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34 | (1) |
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How does ATP drive other types of work? |
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35 | (1) |
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High-energy phosphoryl groups are transferred by enzymes known as kinases |
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35 | (1) |
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Energy considerations in covalent and noncovalent bonds |
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36 | (2) |
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Noncovalent bonds are the basis of molecular recognition and self-assembly of life forms |
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36 | (1) |
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Noncovalent bonds are also important in the structures of individual protein molecules and other macromolecules |
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37 | (1) |
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Types of noncovalent bonds |
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37 | (1) |
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37 | (1) |
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37 | (1) |
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38 | (1) |
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38 | (1) |
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Appendix: Buffers and pKa values |
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38 | (7) |
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pKa values and their relationship to buffers |
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39 | (1) |
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40 | (1) |
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41 | (1) |
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41 | (4) |
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Part 2 Structure and function of proteins and membranes |
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Chapter 4 The structure of proteins |
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45 | (27) |
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Structures of the 20 amino acids used in protein synthesis |
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45 | (3) |
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The different levels of protein structure - primary, secondary, tertiary, and quaternary |
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48 | (7) |
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Primary structure of proteins |
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48 | (2) |
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Secondary structure of proteins |
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50 | (2) |
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Tertiary structure of proteins |
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52 | (3) |
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Quaternary structure of proteins |
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55 | (1) |
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Protein homologies and evolution |
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55 | (1) |
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56 | (1) |
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56 | (1) |
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56 | (1) |
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Conjugated proteins and post-translational modifications of proteins |
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56 | (1) |
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Extracellular matrix proteins |
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57 | (6) |
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57 | (2) |
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59 | (1) |
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Structure of proteoglycans |
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59 | (1) |
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Fibronectin and integrins connect the extracellular matrix to the interior of the cell |
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60 | (3) |
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Myoglobin and haemoglobin illustrate how protein structure is related to function |
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63 | (9) |
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63 | (1) |
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64 | (1) |
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Binding of oxygen to haemoglobin |
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64 | (1) |
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Theoretical models to explain protein allostery |
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65 | (1) |
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Mechanism of the allosteric change in haemoglobin |
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66 | (1) |
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The essential role of 2,3-bisphosphoglycerate (BPG) in haemoglobin function |
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66 | (2) |
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Effect of pH on oxygen binding to haemoglobin |
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68 | (1) |
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69 | (1) |
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70 | (1) |
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71 | (1) |
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Chapter 5 Methods in protein investigation |
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72 | (15) |
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72 | (5) |
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73 | (1) |
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SDS polyacrylamide gel electrophoresis (SDS-PAGE) |
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74 | (1) |
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Nondenaturing polyacrylamide gel electrophoresis |
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75 | (2) |
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The principles of mass spectrometry |
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77 | (1) |
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Mass spectrometers consist of three principal components |
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77 | (1) |
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Ionization methods for protein and peptide mass spectrometry |
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77 | (1) |
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78 | (1) |
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Types of mass spectrometers |
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78 | (1) |
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Applications of mass spectrometry |
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78 | (1) |
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Molecular weight determination of proteins |
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78 | (1) |
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Identification of proteins using mass spectrometry without sequencing |
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79 | (1) |
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Identification of proteins by limited sequencing and database searching |
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79 | (1) |
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Analysis of post-translational modification of proteins |
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79 | (1) |
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Methods of sequencing protein |
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79 | (2) |
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79 | (1) |
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Sequence prediction of proteins from gene DNA sequences |
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79 | (1) |
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Sequencing by mass spectrometry |
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80 | (1) |
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Determination of the three-dimensional structure of proteins |
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81 | (1) |
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81 | (1) |
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Nuclear magnetic resonance spectroscopy |
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81 | (1) |
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82 | (1) |
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An exercise in obtaining a 3-D structure from a protein database |
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82 | (1) |
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82 | (1) |
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Bioinformatics and databases |
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83 | (4) |
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85 | (1) |
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85 | (1) |
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85 | (2) |
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87 | (16) |
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87 | (3) |
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The nature of enzyme catalysis |
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88 | (1) |
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The induced-fit mechanism of enzyme catalysis |
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89 | (1) |
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90 | (4) |
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Hyperbolic kinetics of a `classical' enzyme |
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90 | (2) |
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92 | (2) |
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General properties of enzymes |
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94 | (2) |
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94 | (1) |
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94 | (1) |
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Enzyme cofactors and activators |
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94 | (1) |
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Covalent modification of enzymes |
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94 | (1) |
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95 | (1) |
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Effect of temperature on enzymes |
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95 | (1) |
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Effect of inhibitors on enzymes |
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95 | (1) |
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Competitive and noncompetitive inhibitors |
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95 | (1) |
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Mechanism of enzyme catalysis |
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96 | (7) |
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Mechanism of the chymotrypsin reaction |
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96 | (1) |
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The catalytic triad of the active site |
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97 | (1) |
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The reactions at the catalytic site of chymotrypsin |
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98 | (1) |
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What is the function of the aspartate residue of the catalytic triad? |
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98 | (1) |
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99 | (1) |
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A brief description of other types of protease |
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100 | (1) |
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101 | (1) |
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102 | (1) |
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102 | (1) |
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Chapter 7 The cell membrane and membrane proteins |
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103 | (24) |
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Basic lipid architecture of membranes |
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103 | (7) |
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The polar lipid constituents of cell membranes |
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103 | (2) |
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What are the polar groups attached to the phosphatidic acid? |
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105 | (2) |
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Membrane lipid nomenclature |
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107 | (1) |
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What is the advantage of having so many different types of membrane lipid? |
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107 | (1) |
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The fatty acid components of membrane lipids |
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108 | (1) |
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What is cholesterol doing in membranes? |
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108 | (1) |
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The self-sealing character of the lipid bilayer |
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109 | (1) |
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Permeability characteristics of the lipid bilayer |
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109 | (1) |
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Membrane proteins and membrane structure |
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110 | (1) |
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Structures of integral membrane proteins |
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111 | (2) |
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Anchoring of peripheral membrane proteins to membranes |
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112 | (1) |
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112 | (1) |
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113 | (14) |
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113 | (3) |
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Passive transport or facilitated diffusion |
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116 | (1) |
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116 | (1) |
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Mechanism of the selectivity of the potassium channel |
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117 | (1) |
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Nerve-impulse transmission |
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118 | (1) |
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How does acetylcholine binding to a membrane receptor result in a nerve impulse? |
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119 | (3) |
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Myelinated neurons permit more rapid nerve-impulse transmission |
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122 | (1) |
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Role of the cell membrane in maintaining the shape of the cell |
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123 | (2) |
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Cell-cell interactions - tight junctions, gap junctions, and cellular adhesive proteins |
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125 | (1) |
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125 | (1) |
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126 | (1) |
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126 | (1) |
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Chapter 8 Muscle contraction, the cytoskeleton, and molecular motors |
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127 | (20) |
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127 | (1) |
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A reminder of conformational changes in proteins |
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127 | (1) |
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Types of muscle cell and their energy supply |
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127 | (4) |
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Structure of skeletal striated muscle |
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128 | (2) |
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How does the myosin head convert the energy of ATP hydrolysis into mechanical force on the actin filament? |
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130 | (1) |
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Control of voluntary striated muscle |
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131 | (1) |
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How does Ca2+trigger contraction? |
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131 | (1) |
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Smooth muscle differs in structure and control from striated muscle |
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132 | (3) |
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Control of smooth muscle contractions |
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134 | (1) |
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135 | (1) |
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135 | (1) |
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The cytoskeleton is in a constant dynamic state |
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136 | (1) |
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The role of actin and myosin in nonmuscle cells |
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136 | (2) |
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Assembly and collapse of actin filaments |
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137 | (1) |
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The role of actin and myosin in cell movement |
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138 | (1) |
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The role of actin and myosin in intracellulartransport of vesicles |
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138 | (1) |
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Microtubules, cell movement, and intracellular transport |
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138 | (2) |
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140 | (7) |
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142 | (1) |
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142 | (1) |
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143 | (4) |
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Part 3 Metabolism and nutrition |
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Chapter 9 General principles of nutrition |
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147 | (9) |
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The requirement for energy and nutrients |
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147 | (5) |
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148 | (1) |
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148 | (1) |
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149 | (1) |
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149 | (3) |
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Guidelines for a healthy diet |
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152 | (1) |
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Regulation of food intake |
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152 | (4) |
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Hunger appetite and satiety |
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152 | (1) |
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Integration of hunger and satiety signals by the hypothalamus |
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153 | (1) |
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154 | (1) |
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155 | (1) |
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155 | (1) |
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Chapter 10 Food digestion, absorption, and distribution to the tissues |
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156 | (17) |
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156 | (1) |
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157 | (1) |
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Anatomy of the digestive tract |
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158 | (1) |
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What are the energy considerations in digestion and absorption? |
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158 | (1) |
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A major problem in digestion - why Doesn't the body digest itself? |
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158 | (1) |
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158 | (3) |
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HCI production in the stomach |
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159 | (1) |
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Pepsin, the proteotytic enzyme or the stomach |
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159 | (1) |
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Completion of protein digestion in the small intestine |
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159 | (1) |
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Activation of the pancreatic proenzymes |
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160 | (1) |
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Absorption of amino acids into the bloodstream |
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160 | (1) |
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Digestion of carbohydrates |
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161 | (2) |
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Structure of carbohydrates |
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161 | (1) |
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161 | (1) |
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162 | (1) |
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162 | (1) |
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Absorption of monosaccharides |
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163 | (1) |
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Digestion and absorption of fat |
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163 | (2) |
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Resynthesis of TAG in intestinal cells |
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164 | (1) |
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164 | (1) |
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Digestion of other components of food |
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165 | (1) |
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Storage of food components in the body |
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166 | (7) |
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How are the different food components stored in cells? |
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166 | (1) |
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Characteristics of different tissues in terms of energy metabolism |
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167 | (2) |
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Overall control of fuel distribution in the body by hormones |
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169 | (1) |
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169 | (1) |
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169 | (1) |
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Prolonged fasting and starvation |
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170 | (1) |
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The emergency situation - fight or flight |
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170 | (1) |
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170 | (1) |
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171 | (1) |
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171 | (2) |
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Chapter 11 Mechanisms of transport, storage, and mobilization of dietary components |
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173 | (18) |
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Glucose traffic in the body |
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173 | (7) |
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Mechanism of glycogen synthesis |
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173 | (2) |
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Breakdown of glycogen to release glucose into the blood |
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175 | (2) |
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Key issues in the interconversion of glucose and glycogen |
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177 | (1) |
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The liver has glucokinase and the other tissues, hexokinase |
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177 | (2) |
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What happens to other sugars absorbed from the intestine? |
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179 | (1) |
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Amino acid traffic in the body (in terms of fuel logistics) |
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180 | (1) |
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Fat and cholesterol movement in the body: an overview |
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181 | (1) |
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Utilization of cholesterol in the body |
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181 | (1) |
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Fat and cholesterol traffic in the body: lipoproteins |
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182 | (9) |
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182 | (1) |
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Lipoproteins involved in fat and cholesterol movement in the body |
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183 | (1) |
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Metabolism of chylomicrons |
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183 | (1) |
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Metabolism of VLDL: TAG and cholesterol transport from the liver |
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183 | (5) |
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Release of FFA from adipose cells |
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188 | (1) |
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How are FFA carried in the blood? |
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188 | (1) |
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189 | (1) |
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189 | (1) |
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190 | (1) |
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Chapter 12 Principles of energy release from food |
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191 | (11) |
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Overview of glucose metabolism |
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191 | (2) |
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Biological oxidation and hydrogen-transfer systems |
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191 | (2) |
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Energy release from glucose |
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193 | (4) |
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The main stages of glucose oxidation |
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193 | (1) |
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Stage 1 in the release of energy from glucose: glycolysis |
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193 | (1) |
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Stage 2 of glucose oxidation: the TCA cycle |
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194 | (2) |
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Stage 3 of glucose oxidation: electron transport to oxygen |
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196 | (1) |
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The electron transport chain - a hierarchy of electron carriers |
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196 | (1) |
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Energy release from oxidation of fat |
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197 | (2) |
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Energy release from oxidation of amino acids |
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199 | (1) |
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The interconvertibility of fuels |
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199 | (3) |
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200 | (1) |
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201 | (1) |
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Chapter 13 Glycolysis, the TCA cycle, and the electron transport system |
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202 | (28) |
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202 | (5) |
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202 | (1) |
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ATP is needed at the beginning of glycolysis |
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202 | (3) |
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Interconversion of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate |
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205 | (1) |
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Glyceraldehyde-3-phosphate dehydrogenase - an oxidation linked to ATP synthesis |
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205 | (1) |
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The final steps in glycolysis |
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206 | (1) |
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207 | (1) |
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The ATP balance sheet from glycolysis |
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207 | (1) |
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Transport of pyruvate into the mitochondria |
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207 | (1) |
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Conversion of pyruvate to acetyl-CoA - a preliminary step before the TCA cycle |
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207 | (2) |
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Components involved in the pyruvate dehydrogenase reaction |
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209 | (1) |
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209 | (6) |
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A simplified version of the TCA cycle |
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210 | (1) |
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Mechanisms of the TCA cycle reactions |
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210 | (2) |
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Generation of GTP coupled to splitting of succinyl-CoA |
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212 | (1) |
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What determines the direction of the TCA cycle? |
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213 | (1) |
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Stoichiometry of the cycle |
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214 | (1) |
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How is the concentration of TCA cycle intermediates maintained? |
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214 | (1) |
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Stage 3 the electron transport chain that conveys electrons from NADH and FADH2 to oxygen |
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215 | (15) |
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The electron transport chain |
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215 | (2) |
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Oxidative phosphorylation - the generation of ATP coupled to electron transport |
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217 | (2) |
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219 | (1) |
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ATP synthesis by ATP synthase is driven by the proton gradient |
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220 | (1) |
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Structure of ATP synthase |
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221 | (1) |
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The F1 unit and its role in the conversion of ADP+Pi to ATP |
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221 | (1) |
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Structure of the F0 unit and its role |
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222 | (1) |
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Mechanism by which proton flow causes rotation of F0 |
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223 | (2) |
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Transport of ADP into mitochondria and ATP out |
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225 | (1) |
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Reoxidation of cytosolic NADH from glycolysis by electron shuttle systems |
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225 | (1) |
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The balance sheet of ATP production by electron transport |
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226 | (1) |
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Yield of ATP from the oxidation of a molecule of glucose to CO2 and H2O |
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227 | (1) |
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Is ATP production the only use that is made of the potential energy in the proton-motive force? |
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227 | (1) |
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228 | (1) |
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229 | (1) |
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229 | (1) |
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Chapter 14 Energy release from fat |
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230 | (7) |
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Mechanism of acetyl-CoA formation from fatty acids |
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230 | (3) |
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`Activation' of fatty acids by formation of fatty acyl-CoA derivatives |
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230 | (1) |
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Transport of fatty acyl-CoA derivatives into mitochondria |
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231 | (1) |
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Conversion of fatty acyl-CoA into acetyl-CoA molecules inside the mitochondrion by β-oxidation |
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232 | (1) |
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Energy yield from fatty acid oxidation |
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232 | (1) |
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Oxidation of unsaturated fat |
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233 | (1) |
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Oxidation of odd-numbered carbon-chain fatty acids |
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233 | (1) |
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Ketogenesis in starvation and type 1 diabetes mellitis |
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234 | (3) |
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How is acetoacetate made from acetyl-CoA? |
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234 | (1) |
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Peroxisomal oxidation of fatty acids |
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235 | (1) |
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235 | (1) |
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235 | (1) |
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236 | (1) |
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236 | (1) |
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Chapter 15 An alternative pathway of glucose oxidation. The pentose phosphate pathway |
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237 | (6) |
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The pentose phosphate pathway has two main parts |
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237 | (6) |
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The oxidative part produces equal amounts of ribose-5-phosphate and NADPH |
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238 | (1) |
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Conversion of surplus ribose-5-phosphate into glucose-6-phosphate |
|
|
238 | (2) |
|
Conversion of glucose-6-phosphate into ribose-5-phosphate without NADPH generation |
|
|
240 | (1) |
|
Generation of NADPH without net production of ribose-5-phosphate |
|
|
240 | (1) |
|
Why is the pentose phosphate pathway so important in the erythrocyte? |
|
|
240 | (1) |
|
|
241 | (1) |
|
|
242 | (1) |
|
|
242 | (1) |
|
Chapter 16 Synthesis of glucose (gluconeogenesis) |
|
|
243 | (8) |
|
Mechanism of glucose synthesis from pyruvate |
|
|
243 | (1) |
|
What are the sources of pyruvate or oxaloacetate used by the liver for gluconeogenesis? |
|
|
244 | (2) |
|
Synthesis of glucose from glycerol |
|
|
246 | (1) |
|
Synthesis of glucose from propionate |
|
|
247 | (1) |
|
Effects of ethanol metabolism on gluconeogenesis |
|
|
247 | (1) |
|
Synthesis of glucose via the glyoxylate cycle in bacteria and plants |
|
|
248 | (1) |
|
|
249 | (1) |
|
|
250 | (1) |
|
|
250 | (1) |
|
Chapter 17 Synthesis of fat and related compounds |
|
|
251 | (14) |
|
Mechanism of fat synthesis |
|
|
251 | (5) |
|
General principles of the process |
|
|
251 | (1) |
|
Synthesis of malonyl-CoA is the first step |
|
|
251 | (1) |
|
The acyl carrier protein (ACP) and the β-ketoacyl synthase |
|
|
252 | (1) |
|
Mechanism of fatty acyl-CoA synthesis |
|
|
252 | (1) |
|
Organization of the process of fatty acid synthesis |
|
|
252 | (2) |
|
The reductive steps in fatty acid synthesis |
|
|
254 | (1) |
|
Fatty acid synthesis takes place in the cytosol |
|
|
254 | (2) |
|
Synthesis of unsaturated fatty acids |
|
|
256 | (1) |
|
Synthesis of TAG and membrane lipids from fatty acids |
|
|
256 | (1) |
|
Synthesis of new membrane lipid bilayer |
|
|
257 | (2) |
|
Synthesis of glycerophospholipids |
|
|
257 | (2) |
|
Synthesis of new membrane lipid bilayer |
|
|
259 | (1) |
|
Synthesis of prostaglandins and related compounds |
|
|
259 | (6) |
|
The prostaglandins and thromboxanes |
|
|
261 | (1) |
|
|
262 | (1) |
|
|
262 | (1) |
|
Conversion of cholesterol into steroid hormones |
|
|
262 | (1) |
|
|
263 | (1) |
|
|
263 | (1) |
|
|
263 | (2) |
|
Chapter 18 Nitrogen metabolism: amino acid metabolism |
|
|
265 | (16) |
|
Nitrogen balance of the body |
|
|
266 | (1) |
|
General metabolism of amino acids |
|
|
266 | (3) |
|
Aspects of amino acid metabolism |
|
|
266 | (1) |
|
Glutamate dehydrogenase has a central role in the deamination of amino acids |
|
|
267 | (2) |
|
What happens to the amino group after deamination? The urea cycle |
|
|
269 | (6) |
|
Mechanism of arginine synthesis |
|
|
270 | (1) |
|
Conversion of citrulline to arginine |
|
|
270 | (1) |
|
Transport of the amino nitrogen from extrahepatic tissues to the liver |
|
|
271 | (1) |
|
Diseases due to urea cycle deficiencies |
|
|
272 | (1) |
|
Alternatives to urea formation exist in different animals |
|
|
272 | (1) |
|
Fate of the oxo-acid or carbon skeletons of deaminated amino acids |
|
|
273 | (1) |
|
Genetic errors in amino acid metabolism cause diseases |
|
|
273 | (1) |
|
Methionine and transfer of methyl groups |
|
|
274 | (1) |
|
|
275 | (1) |
|
|
275 | (1) |
|
Synthesis of aspartic acid and alanine |
|
|
275 | (1) |
|
|
275 | (1) |
|
|
275 | (1) |
|
Haem and its synthesis from glycine |
|
|
275 | (6) |
|
|
276 | (1) |
|
Synthesis of adrenaline and noradrenaline |
|
|
277 | (2) |
|
|
279 | (1) |
|
|
280 | (1) |
|
|
280 | (1) |
|
Chapter 19 Nitrogen metabolism: nucleotide metabolism |
|
|
281 | (13) |
|
Structure and nomenclature of nucleotides |
|
|
281 | (2) |
|
The sugar component of nucleotides |
|
|
281 | (1) |
|
The base component of nucleotides |
|
|
282 | (1) |
|
Attachment of the bases in nucleotides |
|
|
282 | (1) |
|
Synthesis of purine and pyrimidine nucleotides |
|
|
283 | (7) |
|
|
283 | (4) |
|
The purine salvage pathway |
|
|
287 | (1) |
|
Formation of uric acid from purines |
|
|
287 | (1) |
|
Control of purine nucleotide synthesis |
|
|
288 | (1) |
|
Synthesis of pyrimidine nucleotides |
|
|
288 | (1) |
|
How are deoxyribonucleotides formed? |
|
|
289 | (1) |
|
Medical effects of folate deficiencies |
|
|
290 | (4) |
|
Thymidylate synthesis is targeted by anticancer agents such as methotrexate |
|
|
290 | (2) |
|
|
292 | (1) |
|
|
293 | (1) |
|
|
293 | (1) |
|
Chapter 20 Mechanisms of metabolic control and their applications to metabolic integration |
|
|
294 | (28) |
|
Why are controls necessary? |
|
|
294 | (1) |
|
The potential clanger of futile cycles in metabolism |
|
|
294 | (1) |
|
How are enzyme activities controlled? |
|
|
295 | (1) |
|
Metabolic control by varying the amounts of enzymes is relatively slow |
|
|
295 | (1) |
|
Metabolic control by regulation of the activities of enzymes in the cell can be very rapid |
|
|
296 | (1) |
|
Which enzymes in metabolic pathways are regulated? |
|
|
296 | (1) |
|
The nature of control enzymes |
|
|
296 | (1) |
|
Allosteric control of enzymes |
|
|
296 | (1) |
|
The mechanism of allosteric control of enzymes and its reversibility |
|
|
297 | (1) |
|
Allosteric control is a tremendously powerful metabolic concept |
|
|
297 | (1) |
|
Control of enzyme activity by phosphorylation |
|
|
297 | (1) |
|
Protein kinases and phosphatases are key players in control mechanisms |
|
|
297 | (1) |
|
Control by phosphorylation usually depends on chemical signals from other cells |
|
|
298 | (1) |
|
General aspects of the hormonal control of metabolism |
|
|
298 | (2) |
|
How do glucagon, adrenaline, and insulin work? |
|
|
298 | (1) |
|
What is a second messenger? |
|
|
299 | (1) |
|
The intracellular second messenger for glucagon and adrenaline is cyclic AMP |
|
|
299 | (1) |
|
Control of carbohydrate metabolism |
|
|
300 | (1) |
|
Control of glucose uptake into cells |
|
|
300 | (1) |
|
Control of glycogen metabolism |
|
|
301 | (9) |
|
Control of glycogen breakdown in muscle |
|
|
302 | (1) |
|
Mechanism of muscle phosphorylase activation by cAMP |
|
|
303 | (1) |
|
Control of glycogen breakdown in the liver |
|
|
304 | (1) |
|
Reversal of phosphorylase activation in muscle and liver |
|
|
304 | (1) |
|
The switchover from glycogen degradation to glycogen synthesis |
|
|
304 | (1) |
|
Mechanism of insulin activation of glycogen synthase |
|
|
304 | (1) |
|
Control of glycolysis and gluconeogenesis |
|
|
305 | (2) |
|
Muscle and liver PFK2 enzymes are different |
|
|
307 | (1) |
|
Fructose metabolism and its control differs from that of glucose |
|
|
308 | (1) |
|
Control of pyruvate dehydrogenase, the TCA cycle, and oxidative phosphorylation |
|
|
309 | (1) |
|
Controls of fatty acid oxidation and synthesis |
|
|
310 | (1) |
|
|
310 | (1) |
|
Degradation of acetyl-CoA carboxylase is another type of control of fat metabolism |
|
|
310 | (1) |
|
Hormonal controls on fat metabolism |
|
|
310 | (1) |
|
Responses to metabolic stress |
|
|
311 | (2) |
|
Response to low ATP concentrations by AMP-activated protein kinase |
|
|
311 | (1) |
|
Response of cells to oxygen deprivation |
|
|
312 | (1) |
|
Mechanism of the response to hypoxia |
|
|
312 | (1) |
|
Integration of metabolism: the fed and fasting state, and diabetes mellitus |
|
|
313 | (9) |
|
Metabolism in the fed state |
|
|
313 | (1) |
|
Metabolism in the fasting state |
|
|
314 | (1) |
|
Metabolism in prolonged starvation |
|
|
315 | (1) |
|
Metabolism in type 1 diabetes mellitus |
|
|
316 | (2) |
|
|
318 | (2) |
|
|
320 | (1) |
|
|
321 | (1) |
|
Chapter 21 Raising electrons of water back up the energy scale -- photosynthesis |
|
|
322 | (13) |
|
|
322 | (1) |
|
Site of photosynthesis-the chloroplast |
|
|
322 | (1) |
|
The light-dependent reactions of photosynthesis |
|
|
323 | (4) |
|
The photosynthetic apparatus and its organization in the thylakoid membrane |
|
|
323 | (1) |
|
How is light energy captured? |
|
|
324 | (1) |
|
Mechanism of light-dependent reduction of NADP+ |
|
|
325 | (1) |
|
|
325 | (1) |
|
|
326 | (1) |
|
|
326 | (1) |
|
The `dark reactions' of photosynthesis -- the Calvin cycle |
|
|
327 | (8) |
|
How is CO2 converted into carbohydrate? |
|
|
327 | (1) |
|
Rubisco has an apparent efficiency problem |
|
|
328 | (1) |
|
|
329 | (1) |
|
|
330 | (1) |
|
|
331 | (1) |
|
|
331 | (4) |
|
Part 4 Information storage and utilization |
|
|
|
|
335 | (17) |
|
|
335 | (1) |
|
The structures of DNA and RNA |
|
|
335 | (1) |
|
DNA is chemically a very simple molecule |
|
|
335 | (1) |
|
DNA and RNA are both nucleic acids |
|
|
336 | (1) |
|
The primary structure of DNA |
|
|
336 | (2) |
|
There are four different nucleotide bases in DNA |
|
|
336 | (1) |
|
Attachment of the bases to deoxyribose |
|
|
336 | (1) |
|
The physical properties of the polynucleotide components |
|
|
337 | (1) |
|
Structure of the polynucleotide of DNA |
|
|
337 | (1) |
|
Deoxyribose makes DNA more stable than RNA |
|
|
338 | (1) |
|
Thymine instead of uracil allows DNA repair |
|
|
338 | (1) |
|
|
338 | (5) |
|
Complementary base pairing |
|
|
339 | (3) |
|
DNA chains are antiparallel; what does this mean? |
|
|
342 | (1) |
|
|
343 | (1) |
|
|
343 | (1) |
|
|
343 | (1) |
|
|
343 | (1) |
|
The eukaryotic genome: chromosomes |
|
|
343 | (1) |
|
|
344 | (1) |
|
The structure of protein-coding genes |
|
|
344 | (1) |
|
|
344 | (1) |
|
Protein-coding regions of genes in eukaryotes are split up into different sections |
|
|
344 | (1) |
|
Gene duplication facilitates evolution of new genes |
|
|
345 | (1) |
|
Most of the human genome does not encode proteins |
|
|
345 | (2) |
|
Mobile genetic elements: transposons and retroviruses |
|
|
346 | (1) |
|
|
346 | (1) |
|
|
347 | (1) |
|
|
347 | (1) |
|
|
347 | (5) |
|
The prokaryotic genome is compacted in the cell |
|
|
347 | (1) |
|
How is eukaryotic DNA packed into a nucleus? |
|
|
347 | (1) |
|
The tightness of DNA packaging changes during the cell cycle |
|
|
348 | (1) |
|
The tightness of DNA packing can regulate gene activity |
|
|
349 | (1) |
|
|
349 | (1) |
|
|
350 | (1) |
|
|
350 | (2) |
|
Chapter 23 DNA synthesis, repair, and recombination |
|
|
352 | (23) |
|
Overall principle of DNA replication |
|
|
352 | (1) |
|
Control of initiation of DNA replication in E. coli |
|
|
353 | (1) |
|
Initiation and regulation of DNA replication in eukaryotes |
|
|
353 | (1) |
|
Unwinding the DNA double helix and supercoiling |
|
|
353 | (3) |
|
How are positive supercoils removed ahead of the replication fork? |
|
|
354 | (2) |
|
The basic enzymic reaction catalysed by DNA polymerases |
|
|
356 | (1) |
|
How does a new strand get started? |
|
|
357 | (1) |
|
The polarity problem in DNA replication |
|
|
357 | (1) |
|
Mechanism of Okazaki fragment synthesis |
|
|
358 | (3) |
|
Enzyme complex at the replication fork in E. coli |
|
|
358 | (2) |
|
Processing the Okazaki fragments |
|
|
360 | (1) |
|
The machinery in the eukaryotic replication fork |
|
|
361 | (1) |
|
Telomeres solve the problem of replicating the ends of eukaryotic chromosomes |
|
|
361 | (2) |
|
How is telomeric DNA synthesized? |
|
|
362 | (1) |
|
Telomeres stabilize the ends of linear chromosomes |
|
|
363 | (1) |
|
Telomere shortening correlates with ageing |
|
|
363 | (1) |
|
How is fidelity achieved in DNA replication? |
|
|
363 | (2) |
|
Exonucleolytic proofreading |
|
|
364 | (1) |
|
Methyl-directed mismatch repair |
|
|
364 | (1) |
|
Repair of DNA damage in E. coil |
|
|
365 | (2) |
|
DNA damage repair in eukaryotes |
|
|
367 | (1) |
|
|
367 | (3) |
|
Mechanism of homologous recombination |
|
|
369 | (1) |
|
Recombination in eukaryotes |
|
|
369 | (1) |
|
Replication of mitochondrial DNA |
|
|
370 | (1) |
|
DNA synthesis by reverse transcription in retroviruses |
|
|
371 | (4) |
|
|
372 | (1) |
|
|
373 | (1) |
|
|
373 | (2) |
|
Chapter 24 Gene transcription |
|
|
375 | (12) |
|
|
375 | (2) |
|
|
375 | (1) |
|
|
375 | (1) |
|
Some general properties of mRNA |
|
|
376 | (1) |
|
Some essential terminology |
|
|
377 | (1) |
|
Gene transcription in E. coli |
|
|
377 | (2) |
|
Phases of gene transcription |
|
|
377 | (2) |
|
The rate of gene transcription initiation in prokaryotes |
|
|
379 | (1) |
|
Control of transcription by different sigma factors |
|
|
379 | (1) |
|
Gene transcription in eukaryotic cells |
|
|
379 | (4) |
|
Eukaryotic RNA polymerases |
|
|
379 | (1) |
|
How is transcription initiated at eukaryotic promoters? |
|
|
380 | (1) |
|
Type II eukaryotic gene promoters |
|
|
380 | (1) |
|
Elongation of the transcript requires Pol II modification |
|
|
381 | (1) |
|
Capping the RNA transcribed by RNA polymerase II |
|
|
381 | (1) |
|
Split genes and RNA splicing |
|
|
382 | (1) |
|
Ribozymes and self-splicing of RNA |
|
|
383 | (2) |
|
Termination of transcription in eukaryotic cells: 3'polyadenylation |
|
|
384 | (1) |
|
|
384 | (1) |
|
Transcription of nonprotein-coding genes |
|
|
385 | (1) |
|
Gene transcription in mitochondria |
|
|
385 | (2) |
|
|
385 | (1) |
|
|
386 | (1) |
|
|
386 | (1) |
|
Chapter 25 Protein synthesis and controlled protein breakdown |
|
|
387 | (23) |
|
Essential basis of the process of protein synthesis |
|
|
387 | (1) |
|
|
388 | (1) |
|
A preliminary simplified look at the chemistry of peptide synthesis |
|
|
388 | (5) |
|
ATP and GTP hydrolysis in translation |
|
|
389 | (1) |
|
How are the codons translated? |
|
|
390 | (1) |
|
|
390 | (1) |
|
|
390 | (2) |
|
How are amino acids attached to tRNA molecules? |
|
|
392 | (1) |
|
|
393 | (1) |
|
Initiation of translation |
|
|
394 | (2) |
|
Initiation of translation in E. coli |
|
|
394 | (2) |
|
Initiation factors in E. coli |
|
|
396 | (1) |
|
Once initiation is achieved, elongation is the next step |
|
|
396 | (2) |
|
Elongation factors in E. coli |
|
|
396 | (1) |
|
Mechanism of elongation in E. coli |
|
|
396 | (2) |
|
How is accuracy of translation achieved? |
|
|
398 | (1) |
|
Mechanism of translocation on the E. coli ribosome |
|
|
398 | (1) |
|
Termination of protein synthesis in E. coli |
|
|
399 | (1) |
|
Physical structure of the ribosome |
|
|
399 | (1) |
|
|
400 | (1) |
|
Protein synthesis in eukaryotes |
|
|
400 | (2) |
|
Incorporation of selenocysteine into proteins |
|
|
402 | (1) |
|
Protein synthesis in mitochondria |
|
|
402 | (1) |
|
Folding up of the polypeptide chain |
|
|
402 | (1) |
|
Chaperones (heat shock proteins) |
|
|
403 | (1) |
|
Mechanism of action of molecular chaperones |
|
|
403 | (2) |
|
Enzymes involved in protein folding |
|
|
404 | (1) |
|
Protein folding and prion diseases |
|
|
405 | (1) |
|
Programmed destruction of protein by proteasomes |
|
|
405 | (5) |
|
|
405 | (1) |
|
The structure of proteasomes |
|
|
406 | (1) |
|
Proteins destined for destruction in proteasomes are marked by ubiquitination |
|
|
406 | (1) |
|
The role of proteasomes in the immune system |
|
|
407 | (1) |
|
|
407 | (1) |
|
|
408 | (1) |
|
|
409 | (1) |
|
Chapter 26 Control of gene expression |
|
|
410 | (23) |
|
|
410 | (1) |
|
Gene control in E. coli: the lac operon |
|
|
410 | (1) |
|
Structure of the E. coli lac operon |
|
|
411 | (1) |
|
Transcriptional regulation in eukaryotes |
|
|
412 | (2) |
|
A general overview of the differences in the initiation and control of gene transcription in prokaryotes and eukaryotes |
|
|
412 | (1) |
|
DNA elements involved in eukaryotic gene control |
|
|
413 | (1) |
|
DNA binding by transcription factors |
|
|
414 | (7) |
|
Most transcription factors themselves are regulated |
|
|
418 | (1) |
|
|
418 | (3) |
|
DNA methylation and epigenetic control |
|
|
421 | (1) |
|
Gene control after transcription is initiated: an overview |
|
|
422 | (1) |
|
Gene control post-transcription initiation in prokaryotes |
|
|
422 | (2) |
|
Attenuation in the E. coli trp operon |
|
|
422 | (1) |
|
|
423 | (1) |
|
mRNA stability and the control of gene expression |
|
|
424 | (1) |
|
Determinants of eukaryotic mRNA stability and their role in gene expression control |
|
|
424 | (1) |
|
Translational control mechanisms in eukaryotes |
|
|
425 | (2) |
|
Translational control in iron homeostasis and haem synthesis |
|
|
426 | (1) |
|
Regulation of globin synthesis |
|
|
426 | (1) |
|
Small RNAs and RNA interference |
|
|
427 | (6) |
|
Classes and production of small RNAs in eukaryotes |
|
|
427 | (1) |
|
Molecular mechanism of gene silencing by RNAi |
|
|
427 | (1) |
|
In vivo functions and importance of noncoding RNA |
|
|
428 | (2) |
|
The potential medical and practical importance of RNAi |
|
|
430 | (1) |
|
|
430 | (1) |
|
|
431 | (1) |
|
|
431 | (2) |
|
Chapter 27 Protein sorting and delivery |
|
|
433 | (17) |
|
A preliminary overview of the field |
|
|
433 | (2) |
|
Structure and function of the ER and Golgi apparatus |
|
|
434 | (1) |
|
The importance of the GTP/GDP switch mechanism in protein targeting |
|
|
435 | (1) |
|
Translocation of proteins through the ER membrane |
|
|
436 | (4) |
|
Synthesis of integral membrane proteins |
|
|
437 | (1) |
|
Folding of the polypeptides inside the ER |
|
|
438 | (1) |
|
Glycosylation of proteins in the ER lumen and Golgi apparatus |
|
|
439 | (1) |
|
|
439 | (1) |
|
Proteins to be returned to the ER |
|
|
439 | (1) |
|
Proteins to be secreted from the cell |
|
|
439 | (1) |
|
Proteins are sorted, packaged, and despatched from the ER and Golgi by vesicular transport |
|
|
440 | (1) |
|
Mechanism of COP-coated vesicle formation |
|
|
440 | (1) |
|
How does a vesicle find its target membrane? |
|
|
440 | (1) |
|
Clathrin-coated vesicles transport enzymes from the Golgi to form lysosomes |
|
|
441 | (1) |
|
Posttranslational transport of proteins into organelles |
|
|
441 | (3) |
|
Transport of proteins into mitochondria |
|
|
441 | (1) |
|
Mitochondrial matrix proteins are synthesized as preproteins |
|
|
441 | (2) |
|
Delivery of proteins to mitochondrial membranes and intermembrane space |
|
|
443 | (1) |
|
Nuclear-cytosolic traffic |
|
|
444 | (1) |
|
Why is there a nuclear membrane? |
|
|
444 | (1) |
|
|
444 | (2) |
|
Nuclear localization signals |
|
|
446 | (4) |
|
GTP/GDP exchange imparts directionality to nuclear-cytosolic transport |
|
|
446 | (1) |
|
Regulation of nuclear transport by cell signals and its role in gene control |
|
|
447 | (1) |
|
|
448 | (1) |
|
|
449 | (1) |
|
|
449 | (1) |
|
Chapter 28 Manipulating DNA and genes |
|
|
450 | (27) |
|
|
450 | (4) |
|
Some preliminary considerations |
|
|
450 | (1) |
|
Cutting DNA with restriction endonucleases |
|
|
451 | (1) |
|
|
451 | (1) |
|
Visualizing the separated pieces |
|
|
452 | (1) |
|
Detection of specific DNA fragments by nucleic acid hybridization probes |
|
|
452 | (1) |
|
|
453 | (1) |
|
Chemical synthesis of DNA |
|
|
454 | (1) |
|
|
454 | (2) |
|
The principle of DNA sequencing by the chain-termination method |
|
|
454 | (2) |
|
Amplification of DNA by the polymerase chain reaction |
|
|
456 | (2) |
|
Analysis of multiple gene expression in cells using DNA microarrays |
|
|
457 | (1) |
|
joining DNA to form recombinant molecules |
|
|
458 | (1) |
|
|
459 | (3) |
|
|
459 | (2) |
|
|
461 | (1) |
|
Cloning vectors for larger pieces of DNA |
|
|
462 | (1) |
|
Applications of recombinant DNA technology |
|
|
462 | (9) |
|
Working with RNA and cDNA |
|
|
462 | (1) |
|
Production of human proteins and proteins from other sources |
|
|
463 | (1) |
|
Expressing the cDNA in E. coli |
|
|
463 | (1) |
|
Site-directed mutagenesis |
|
|
464 | (1) |
|
|
464 | (2) |
|
Locating disease-producing genes |
|
|
466 | (1) |
|
|
467 | (1) |
|
The embryonic stem (ES) cell system |
|
|
467 | (1) |
|
|
468 | (2) |
|
Stem cells and potential therapy for human diseases |
|
|
470 | (1) |
|
|
470 | (1) |
|
|
471 | (1) |
|
DNA databases and genomics |
|
|
471 | (6) |
|
|
472 | (1) |
|
|
472 | (1) |
|
|
473 | (4) |
|
|
|
Chapter 29 Cell signalling |
|
|
477 | (30) |
|
|
477 | (2) |
|
Organization of this chapter |
|
|
479 | (1) |
|
What are the signalling molecules? |
|
|
479 | (2) |
|
|
479 | (1) |
|
|
479 | (1) |
|
Cytokines and growth factors |
|
|
480 | (1) |
|
Vitamin D and retinoic acid |
|
|
481 | (1) |
|
Responses mediated by intracellular receptors |
|
|
481 | (1) |
|
Responses mediated by receptors in the cell membrane |
|
|
482 | (3) |
|
There are three main types of membrane-bound receptors |
|
|
482 | (3) |
|
General concepts in cell signalling mechanisms |
|
|
485 | (1) |
|
|
485 | (1) |
|
Binding domains of signal transduction proteins |
|
|
485 | (1) |
|
|
486 | (1) |
|
Examples of signal transduction pathways |
|
|
486 | (1) |
|
Signal transduction pathways from tyrosine kinase receptors |
|
|
486 | (9) |
|
|
486 | (4) |
|
|
490 | (1) |
|
The phosphatidylinositide 3-kinase (PI 3-kinase) pathway and insulin signalling |
|
|
491 | (3) |
|
The JAK/STAT pathways: another type of tyrosine kinase-associated signalling system |
|
|
494 | (1) |
|
G-protein-coupled receptors and associated signal transduction pathways |
|
|
495 | (8) |
|
|
495 | (1) |
|
cAMP as second messenger: adrenaline signalling -- a G-protein pathway |
|
|
496 | (3) |
|
The phosphatidylinositol cascade: another example of a G-protein-coupled receptor that works via a different second messenger |
|
|
499 | (1) |
|
Other roles of calcium in regulation of cellular processes |
|
|
500 | (1) |
|
Vision: a process dependent on a G-protein-coupled receptor |
|
|
501 | (2) |
|
Signal transduction pathway using cGMP as a second messenger |
|
|
503 | (4) |
|
Membrane receptor-mediated pathways |
|
|
503 | (1) |
|
Nitric oxide signalling -- activation of a soluble cytoplasmic guanylate cyclase |
|
|
503 | (2) |
|
|
505 | (1) |
|
|
506 | (1) |
|
|
506 | (1) |
|
Chapter 30 The cell cycle, cell division and cell death |
|
|
507 | (11) |
|
The eukaryotic cell cycle |
|
|
507 | (1) |
|
The cell cycle is divided into separate phases |
|
|
507 | (1) |
|
The cell cycle phases are tightly controlled |
|
|
507 | (1) |
|
|
508 | (1) |
|
Cytokines and growth factor control in the cell cycle |
|
|
508 | (1) |
|
|
508 | (1) |
|
Cell cycle controls depend on the synthesis and destruction of cyclins |
|
|
508 | (1) |
|
Controls in G1 are complex |
|
|
509 | (1) |
|
|
510 | (1) |
|
How is DNA damage detected? |
|
|
510 | (1) |
|
|
510 | (1) |
|
|
510 | (1) |
|
|
510 | (1) |
|
|
511 | (2) |
|
|
511 | (1) |
|
|
511 | (2) |
|
|
513 | (1) |
|
What is the function of apoptosis? |
|
|
513 | (1) |
|
There are two main pathways that initiate apoptosis |
|
|
514 | (4) |
|
Caspase enzymes are the effectors of apoptosis |
|
|
514 | (1) |
|
Mechanism of an intrinsic pathway of apoptosis |
|
|
515 | (1) |
|
Regulation of the intrinsic pathway of apoptosis by Bcl-2 proteins |
|
|
515 | (1) |
|
Mechanism of the extrinsic pathway of apoptosis |
|
|
516 | (1) |
|
|
516 | (1) |
|
|
517 | (1) |
|
|
517 | (1) |
|
|
518 | (9) |
|
|
518 | (1) |
|
Cancer development involves a progression of mutations |
|
|
519 | (1) |
|
Development of colorectal cancer |
|
|
519 | (1) |
|
|
519 | (1) |
|
The types of genetic change involved in cancer |
|
|
520 | (1) |
|
|
521 | (1) |
|
How are oncogenes acquired? |
|
|
521 | (1) |
|
Retroviruses can activate or acquire cellular protooncogenes |
|
|
522 | (1) |
|
|
522 | (1) |
|
Mechanism of protection by the p53 gene |
|
|
523 | (1) |
|
Mechanism of protection by the retinoblastoma gene |
|
|
523 | (1) |
|
Molecular biology advances have potential for development of new cancer therapies |
|
|
523 | (4) |
|
|
524 | (1) |
|
|
524 | (1) |
|
|
524 | (3) |
|
Part 6 Protective mechanisms against disease |
|
|
|
Chapter 32 Special topics: blood clotting, xenobiotic metabolism, reactive oxygen species |
|
|
527 | (9) |
|
Blood clotting (thrombus formation) |
|
|
527 | (3) |
|
What signals the necessity for clot formation? |
|
|
528 | (1) |
|
How does thrombin cause thrombus formation? |
|
|
528 | (1) |
|
Keeping clotting in check |
|
|
528 | (1) |
|
Rat poison, blood clotting, and vitamin K |
|
|
529 | (1) |
|
Protection against ingested foreign chemicals (xenobiotics) |
|
|
530 | (2) |
|
|
530 | (1) |
|
Secondary modification -- addition of a polar group to products of the P450 attack |
|
|
531 | (1) |
|
Medical significance of P450s |
|
|
531 | (1) |
|
|
532 | (1) |
|
Protection against reactive oxygen species |
|
|
532 | (2) |
|
Formation of the superoxide anion and other reactive oxygen species |
|
|
532 | (1) |
|
Mopping up oxygen free radicals with vitamins C and E |
|
|
533 | (1) |
|
Enzymic destruction of superoxide by superoxide dismutase |
|
|
534 | (1) |
|
The glutathione peroxidase-glutathione reductase system |
|
|
534 | (2) |
|
|
534 | (1) |
|
|
535 | (1) |
|
|
535 | (1) |
|
Chapter 33 The immune system |
|
|
536 | (14) |
|
|
536 | (2) |
|
|
536 | (1) |
|
The adaptive immune response |
|
|
536 | (1) |
|
The problem of autoimmune reactions |
|
|
537 | (1) |
|
The cells involved in the immune system |
|
|
537 | (1) |
|
What does the adaptive immune response achieve? |
|
|
537 | (1) |
|
Where is the immune system located? |
|
|
537 | (1) |
|
Antibody-based or humoral immunity |
|
|
538 | (2) |
|
Structure of antibodies (immunoglobulins) |
|
|
538 | (1) |
|
What are the functions of antibodies? |
|
|
539 | (1) |
|
There are different classes of antibodies |
|
|
539 | (1) |
|
Generation of antibody diversity |
|
|
539 | (1) |
|
Activation of B cells to produce antibodies |
|
|
540 | (4) |
|
Deletion of potentially self-reacting B cells in the bone marrow |
|
|
541 | (1) |
|
The theory of clonal selection |
|
|
541 | (1) |
|
B cells must be activated before they can develop into antibody-secreting cells |
|
|
542 | (1) |
|
Affinity maturation of antibodies |
|
|
543 | (1) |
|
|
544 | (1) |
|
Cell-mediated immunity (cytotoxic T cells) |
|
|
544 | (2) |
|
Mechanism of action of cytotoxic T cells |
|
|
545 | (1) |
|
The role of the major histocompatibility complexes (MHCs) in the displaying of peptides on the cell surface |
|
|
545 | (1) |
|
CD proteins reinforce the selectivity of T cell receptors for the two classes of MHCs |
|
|
546 | (1) |
|
Why does the human immune system reject transplanted human cells? |
|
|
546 | (1) |
|
|
546 | (4) |
|
Humanized monoclonal antibodies |
|
|
547 | (1) |
|
|
548 | (1) |
|
|
549 | (1) |
|
|
549 | (1) |
Answers to problems |
|
550 | (27) |
Index of diseases and medically relevant topics |
|
577 | (1) |
Index |
|
578 | |