Essential Biochemistry

Preface xi Part 1 Foundations 1 The Chemical Basis of Life 1 1.1 What Is Biochemistry? 1 1.2 Biological Molecules 3 1.3 Energy and Metabolism 10 1.4 The Origin and Evolution of Life 14 2 Aqueous Chemistry 24 2.1 Water Molecules and Hydrogen Bonds 24 2.2 The Hydrophobic Effect 29 2.3 Acid–Base Chemistry 33 2.4 Tools and Techniques: Buffers 40 2.5 Clinical Connection: Acid–Base Balance in Humans 42 Part 2 Molecular Structure and Function 3 From Genes to Proteins 52 3.1 Nucleotides 52 3.2 Nucleic Acid Structure 56 3.3 The Central Dogma 61 3.4 Genomics 64 3.5 Tools and Techniques: Manipulating DNA 68 4 Protein Structure 85 4.1 Amino Acids, the Building Blocks of Proteins 86 4.2 Secondary Structure: The Conformation of the Peptide Group 94 4.3 Tertiary Structure and Protein Stability 97 4.4 Quaternary Structure 104 4.5 Clinical Connection: Protein Misfolding and Disease 105 4.6 Tools and Techniques: Analyzing Protein Structure 107 5 Protein Function 119 5.1 Myoglobin and Hemoglobin: Oxygen-Binding Proteins 120 5.2 Clinical Connection: Hemoglobin Variants 127 5.3 Structural Proteins 130 5.4 Motor Proteins 141 6 How Enzymes Work 154 6.1 What Is an Enzyme? 154 6.2 Chemical Catalytic Mechanisms 158 6.3 Unique Properties of Enzyme Catalysts 166 6.4 Chymotrypsin in Context 169 6.5 Clinical Connection: Blood Coagulation 173 7 Enzyme Kinetics and Inhibition 183 7.1 Introduction to Enzyme Kinetics 183 7.2 Derivation and Meaning of the Michaelis–Menten Equation 186 7.3 Enzyme Inhibition 194 7.4 Clinical Connection: Drug Development 204 8 Lipids and Membranes 215 8.1 Lipids 215 8.2 The Lipid Bilayer 222 8.3 Membrane Proteins 225 8.4 The Fluid Mosaic Model 228 9 Membrane Transport 235 9.1 The Thermodynamics of Membrane Transport 235 9.2 Passive Transport 240 9.3 Active Transport 245 9.4 Membrane Fusion 248 10 Signaling 260 10.1 General Features of Signaling Pathways 260 10.2 G Protein Signaling Pathways 265 10.3 Receptor Tyrosine Kinases 270 10.4 Lipid Hormone Signaling 274 11 Carbohydrates 283 11.1 Monosaccharides 283 11.2 Polysaccharides 287 11.3 Glycoproteins 291 Part 3 Metabolism 12 Metabolism and Bioenergetics 301 12.1 Food and Fuel 301 12.2 Metabolic Pathways 306 12.3 Free Energy Changes in Metabolic Reactions 314 13 Glucose Metabolism 329 13.1 Glycolysis 330 13.2 Gluconeogenesis 344 13.3 Glycogen Synthesis and Degradation 347 13.4 The Pentose Phosphate Pathway 350 13.5 Clinical Connection: Disorders of Carbohydrate Metabolism 353 14 The Citric Acid Cycle 362 14.1 The Pyruvate Dehydrogenase Reaction 362 14.2 The Eight Reactions of the Citric Acid Cycle 365 14.3 Thermodynamics of the Citric Acid Cycle 372 14.4 Anabolic and Catabolic Functions of the Citric Acid Cycle 375 15 Oxidative Phosphorylation 385 15.1 The Thermodynamics of Oxidation–Reduction Reactions 385 15.2 Mitochondrial Electron Transport 390 15.3 Chemiosmosis 399 15.4 ATP Synthase 401 16 Photosynthesis 411 16.1 Chloroplasts and Solar Energy 411 16.2 The Light Reactions 415 16.3 Carbon Fixation 422 17 Lipid Metabolism 432 17.1 Lipid Transport 432 17.2 Fatty Acid Oxidation 435 17.3 Fatty Acid Synthesis 443 17.4 Synthesis of Other Lipids 452 18 Nitrogen Metabolism 464 18.1 Nitrogen Fixation and Assimilation 464 18.2 Amino Acid Biosynthesis 469 18.3 Amino Acid Catabolism 476 18.4 Nitrogen Disposal: The Urea Cycle 480 18.5 Nucleotide Metabolism 485 19 Regulation of Mammalian Fuel Metabolism 497 19.1 Integration of Fuel Metabolism 498 19.2 Hormonal Control of Fuel Metabolism 501 19.3 Disorders of Fuel Metabolism 507 19.4 Clinical Connection: Cancer Metabolism 511 Part 4 Genetic Information 20 DNA Replication and Repair 519 20.1 The DNA Replication Machinery 519 20.2 Telomeres 528 20.3 DNA Damage and Repair 531 20.4 Clinical Connection: Cancer as a Genetic Disease 538 20.5 DNA Packaging 540 21 Transcription and RNA 551 21.1 Initiating Transcription 552 21.2 RNA Polymerase 562 21.3 RNA Processing 567 22 Protein Synthesis 580 22.1 tRNA and the Genetic Code 580 22.2 Ribosome Structure 586 22.3 Translation 589 22.4 Post-Translational Events 597 Glossary G-1 Odd-Numbered Solutions S-1 Index I-1