LANGE N USMLE ROAD MAP BIOCHEMISTRY This page intentionally left blank LANGE N USMLE ROAD MAP BIOCHEMISTRY RICHARD G. MACDONALD Department of Biochemistry and Molecular Biology University of Nebraska Medical Center Omaha, Nebraska WILLIAM G. CHANEY Department of Biochemistry and Molecular Biology University of Nebraska Medical Center Omaha, Nebraska New York Chicago San Francisco Lisbon London Madrid Mexico City Milan New Delhi San Juan Seoul Singapore Sydney Toronto Copyright © 2007 by The McGraw-Hill Companies, Inc. All rights reserved. Manufactured in the United States of America. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher. 0-07-159319-5 The material in this eBook also appears in the print version of this title: 0-07-144205-7. 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If you’d like more information about this book, its author, or related books and websites, please click here. For more information about this title, click here C O N T E N T S Abbreviations x Acknowledgments xi 1 Physiologic Chemistry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 I. Water 1 II. Electrolytes 1 III. Acids and Bases 2 IV. pH 2 V. Buffers 3 VI. Amphipathic Molecules 6 Clinical Problems 6 Answers 8 2 Protein Structure and Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 I. Amino Acids 9 II.Charge Characteristics of Amino Acids and Proteins 10 III. Protein Structure 11 IV. Collagen 13 V. The Oxygen Binding Proteins—-Myoglobin and Hemoglobin 15 VI. Antibodies 19 Clinical Problems 19 Answers 21 3 The Physiologic Roles of Enzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 I. Enzyme-Catalyzed Reactions 23 II. Enzyme Classification 25 III. Catalysis of Reactions by Enzymes at Physiologic Temperature 26 IV. Mechanisms of Enzyme Catalysis 27 V. Kinetics of Enzyme-Catalyzed Reactions 29 VI. Enzyme Inhibitors 30 VII. Coenzymes and Cofactors 32 VIII. Allosteric Regulation of Enzymes 33 Clinical Problems 34 Answers 36 4 Cell Membranes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 I. Overview of Membrane Structure and Function 37 II. Membrane Components: Lipids 37 III. Organization of the Lipid Bilayer 39 IV. Membrane Components: Proteins 42 V. Membrane Components: Carbohydrates 42 VI. Transmembrane Transport 44 Clinical Problems 48 Answers 50 v N vi Contents 5 Metabolic Interrelationships and Regulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 I. Diet and Nutritional Needs 52 II. Regulation of Metabolic Pathways 54 III. Glucose Homeostasis 56 IV. Metabolism in the Fed State 58 V. Metabolism in the Fasting State 61 VI. Metabolism During Starvation 63 Clinical Problems 66 Answers 68 6 Carbohydrate Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 I. Digestion and Absorption of Dietary Carbohydrates 70 II. Glycolysis 70 III. Regeneration of NAD+ 73 IV. Pentose Phosphate Pathway 76 V. Key Enzymes Regulating Rate-Limiting Steps of Glucose Metabolism 78 VI. Glycogen Metabolism 78 VII. Gluconeogenesis 82 VIII. Metabolism of Galactose and Fructose 85 Clinical Problems 87 Answers 88 7 The TCA Cycle and Oxidative Phosphorylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 I. Overview of the Tricarboxylic Acid (TCA) Cycle 90 II. Biosynthesis of Acetyl CoA 90 III. Steps of the TCA Cycle 92 IV. Regulation of the TCA Cycle 94 V. Role of the TCA Cycle in Metabolic Reactions 94 VI. Synthesis of Oxaloacetate from Pyruvate 95 VII. The Electron Transport Chain 96 VIII. Energy Capture During Electron Transport 97 IX. Energy Yield of Oxidative Phosphorylation 97 X. Inhibitors of ATP Generation 97 Clinical Problems 99 Answers 101 8 Lipid Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 I. Digestion and Absorption of Dietary Fats 103 II. The Lipoproteins: Processing and Transport of Fats 104 III. Functions of Fatty Acids in Physiology 105 IV. Fatty Acid Synthesis 106 V. Fatty Acid Oxidation 109 VI. Metabolism of Ketone Bodies 113 VII. Cholesterol Metabolism 115 VIII. Uptake of Particles and Large Molecules by the Cell 117 Clinical Problems 118 Answers 120 9 Nitrogen Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 I. Digestion of Dietary Proteins 122 II. Metabolism of Ammonia 123 III. The Urea Cycle 124 IV. Catabolism of Amino Acids 126 N Contents vii V. Biosynthesis of Amino Acids 129 VI. Porphyrin Metabolism 131 Clinical Problems 135 Answers 137 10 Nucleic Acid Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 I. Structures and Functions of Nucleotides 139 II. Biosynthesis of Purines 139 III. Biosynthesis of Pyrimidines 142 IV. Degradation of Purine and Pyrimidine Nucleotides 146 V. Salvage Pathways 147 Clinical Problems 148 Answers 149 11 Nucleic Acid Structure and Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 I. Overview of Nucleic Acid Function 151 II. Structure of Chromosomal DNA 152 III. Replication 154 IV. Mutations and DNA Repair 158 V. RNA Structure 160 VI. Transcription 161 Clinical Problems 164 Answers 166 12 Gene Expression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 I. The Genetic Code 168 II. Steps in Translation 168 III. Post-translational Modification of Proteins 173 IV. Regulation of Gene Expression 176 V. Mutations 179 Clinical Problems 181 Answers 183 13 Human Genetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185 I. Overview of Mendelian Inheritance 185 II. Modes of Inheritance in Single-Gene Disorders 186 III. Major Concepts in Human Genetics 192 IV. Population Genetics: The Hardy-Weinberg Law 194 Clinical Problems 195 Answers 198 14 Cellular Signaling and Cancer Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 I. General Principles of Cellular Signaling 200 II. Signaling by G Protein-Coupled Receptors 201 III. Receptor Tyrosine Kinases 206 IV. The Nuclear Receptor Superfamily 207 V. Overview of Cancer Biology 210 VI. Oncogenes and Tumor Suppressor Genes 210 VII. Apoptosis 213 Clinical Problems 215 Answers 217 Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218 This page intentionally left blank