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MetabolismNotesOneSided

MetabolismNotesOneSided - Chem 333 Metabolism Lecture Notes...

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Chem 333: Metabolism Lecture Notes Michael Palmer, Department of Chemistry, University of Waterloo, Canada Third edition, 2008
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Contents About these notes ...................................................................................................... vi Chapter 1 . Introduction ............................................................................................... 1 1.1. Why study metabolism? ................................................................................... 1 1.2. What is this class all about? ................................................................................ 1 1.3. Metabolic diversity ......................................................................................... 2 1.4. Major types of foodstuffs .................................................................................. 2 1.5. The digestive tract ......................................................................................... 4 1.5.1. The stomach ..................................................................................... 4 1.5.2. The pancreas ..................................................................................... 5 1.5.3. The liver .......................................................................................... 5 1.5.4. The small intestine ............................................................................... 6 1.5.5. The lower small intestine and the large intestine ................................................ 7 1.5.6. The portal circulation ............................................................................ 7 1.6. What’s next? ............................................................................................... 7 Chapter 2 . Refresher .................................................................................................. 10 2.1. How enzymes work: Active sites and catalytic mechanisms ............................................. 10 2.2. Classification of Enzymes: Types of enzymatic reactions ................................................ 11 2.3. Energetics of enzyme-catalyzed reactions ................................................................. 11 2.3.1. A simile .......................................................................................... 11 2.4. The role of ATP in enzyme-catalyzed reactions ........................................................... 12 2.5. Regulation of enzyme activity ............................................................................. 12 Chapter 3 . Glycolysis .................................................................................................. 16 3.1. Overview of glucose metabolism .......................................................................... 16 3.2. The place of glycolysis in glucose degradation ........................................................... 16 3.3. Reactions in glycolysis ..................................................................................... 16 3.4. Mechanisms of enzyme catalysis in glycolysis ............................................................ 17 3.4.1. Hexokinase ....................................................................................... 17 3.4.2. Phosphohexose isomerase ....................................................................... 18 3.4.3. Glyceraldehyde-3-phosphate dehydrogenase ................................................... 18 3.4.4. Pyruvate Kinase .................................................................................. 19 3.5. Energy-rich functional groups in substrates of glycolysis ................................................ 20 3.6. Function of glycolysis under anaerobic conditions ....................................................... 21 3.7. Transport and utilization of glucose in the liver and in peripheral cells .................................. 22 Chapter 4 . Catabolism of sugars other than glucose ............................................................... 24 4.1. Metabolism of sucrose and fructose ....................................................................... 24 4.1.1. Genetic defects in fructose assimilation ......................................................... 24 4.2. Metabolism of lactose and galactose ...................................................................... 25 4.2.1. Genetic defects in lactose metabolism .......................................................... 25
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4.3. The polyol pathway ........................................................................................ 26 Chapter 5 . Pyruvate dehydrogenase and the citric acid cycle ..................................................... 29 5.1. Pyruvate dehydrogenase ................................................................................... 29 5.1.1. Catalytic mechanisms in the pyruvate dehydrogenase reaction ................................. 30 5.1.2. Regulation of pyruvate dehydrogenase ......................................................... 31 5.2. The citric acid cycle ........................................................................................ 32 5.2.1. Reactions in the citric acid cycle ................................................................ 33 5.2.2. Regulation of the citric acid cycle ............................................................... 34 Chapter 6 . The respiratory chain .................................................................................... 36 6.1. ATP synthesis can be separated from electron transport .................................................. 36 6.2. The electron transport chain ............................................................................... 37 6.2.1. Redox cofactors in the electron transport chain ................................................. 37 6.2.2. The redox potential of a cofactor measures its affinity for electrons ........................... 38 6.2.3. Hydrogen and electron carriers .................................................................. 39 6.2.4. The ubiquinone cycle ............................................................................ 40 6.2.5. Cytochrome C oxidase (complex IV) ........................................................... 41 6.3. How is electron transport coupled to proton pumping? ................................................... 41 6.3.1. Stoichiometry of proton ejection ................................................................ 42 6.4. ATP synthesis .............................................................................................. 42 6.4.1. The proton-motive force ......................................................................... 43 6.4.2. ATP synthase ..................................................................................... 43 6.5. The ATP yield of oxidative glucose degradation .......................................................... 44 6.6. Auxiliary shuttle systems for the oxidation of cytosolic NADH .......................................... 45 6.7. Regulation of the respiratory chain ........................................................................ 46 Chapter 7 . Gluconeogenesis .......................................................................................... 49 7.1. Reactions in gluconeogenesis .............................................................................. 49 7.2. Glucogenic amino acids serve as carbon sources for gluconeogenesis ................................... 50 7.3. Regulation of gluconeogenesis ............................................................................ 51 7.3.1. The need to control futile cycling ............................................................... 51 7.3.2. ATP, ADP and AMP in the regulation of phosphofructokinase and fructose-1,6-bispho- sphatase .......................................................................................... 51 7.3.3. Hormonal control of phosphofructokinase and fructose-1,6-bisphosphatase .................. 52 7.4. Energetic cost of gluconeogenesis ......................................................................... 52 7.5. The Cori cycle .............................................................................................. 52 7.6. The glyoxylate cycle ....................................................................................... 53 7.7. Additional roles of gluconeogenetic enzymes
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