Fundamentals of Biochemistry: Life at the Molecular Level, 5th Edition [Rental Edition]

Preface xv

Acknowledgments xix

Part I Introduction

1 Introduction to the Chemistry of Life 1

1 The Origin of Life 2

2 Cellular Architecture 5

3 Thermodynamics 11

Box 1-1 Pathways of Discovery Lynn Margulis and the Theory of Endosymbiosis 10

Box 1-2 Perspectives in Biochemistry Biochemical Conventions 12

2 Water 23

1 Physical Properties of Water 24

2 Chemical Properties of Water 31

Box 2-1 Perspectives in Biochemistry the Consequences of Ocean Acidification 34

Box 2-2 Biochemistry in Health and Disease the Blood Buffering System 38

Part II Biomolecules

3 Nucleotides, Nucleic Acids, and Genetic Information 42

1 Nucleotides 43

2 Introduction to Nucleic Acid Structure 46

3 Overview of Nucleic Acid Function 50

4 Nucleic Acid Sequencing 53

5 Manipulating DNA 66

Box 3-1 Pathways to Discovery Francis Collins and the Gene for Cystic Fibrosis 61

Box 3-2 Perspectives in Biochemistry DNA Fingerprinting 73

Box 3-3 Perspectives in Biochemistry Ethical Aspects of Recombinant DNA Technology 75

4 Amino Acids 80

1 Amino Acid Structure 81

2 Stereochemistry 88

3 Amino Acid Derivatives 91

Box 4-1 Pathways to Discovery William C. Rose and the Discovery of Threonine 81

Box 4-2 Perspectives in Biochemistry The RS System 90

Box 4-3 Perspectives in Biochemistry Green Fluorescent Protein 93

5 Proteins: Primary Structure 97

1 Polypeptide Diversity 98

2 Protein Purification and Analysis 99

3 Protein Sequencing 110

4 Protein Evolution 119

Box 5-1 Pathways of Discovery Frederick Sanger and Protein Sequencing 112

6 Proteins: Three-Dimensional Structure 131

1 Secondary Structure 132

2 Tertiary Structure 145

3 Quaternary Structure and Symmetry 158

4 Protein Stability 160

5 Protein Folding 165

Box 6-1 Pathways of Discovery Linus Pauling and Structural Biochemistry 136

Box 6-2 Biochemistry in Health and Disease Collagen Diseases 143

Box 6-3 Perspectives in Biochemistry Thermostable Proteins 162

Box 6-4 Perspectives in Biochemistry Protein Structure Prediction and Protein Design 167

7 Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies 180

1 Oxygen Binding to Myoglobin and Hemoglobin 181

2 Muscle Contraction 200

3 Antibodies 212

Box 7-1 Perspectives in Biochemistry Other Oxygen-Transport Proteins 185

Box 7-2 Pathways of Discovery Max Perutz and the Structure and Function of Hemoglobin 186

Box 7-3 Biochemistry in Health and Disease High-Altitude Adaptation 195

Box 7-4 Pathways of Discovery Hugh Huxley and the Sliding Filament Model 203

Box 7-5 Perspectives in Biochemistry Monoclonal Antibodies 216

8 Carbohydrates 221

1 Monosaccharides 222

2 Polysaccharides 228

3 Glycoproteins 234

Box 8-1 Biochemistry in Health and Disease Lactose Intolerance 228

Box 8-2 Perspectives in Biochemistry Artificial Sweeteners 229

Box 8-3 Biochemistry in Health and Disease Peptidoglycan-Specific Antibiotics 238

9 Lipids and Biological Membranes 245

1 Lipid Classification 246

2 Lipid Bilayers 259

3 Membrane Proteins 262

4 Membrane Structure and Assembly 269

Box 9-1 Biochemistry in Health and Disease Lung Surfactant 251

Box 9-2 Pathways of Discovery Richard Henderson and the Structure of Bacteriorhodopsin 265

Box 9-3 Biochemistry in Health and Disease Tetanus and Botulinum Toxins Specifically Cleave SNAREs 286

10 Membrane Transport 293

1 Thermodynamics of Transport 294

2 Passive-Mediated Transport 295

3 Active Transport 309

Box 10-1 Perspectives in Biochemistry Gap Junctions 306

Box 10-2 Perspectives in Biochemistry Differentiating Mediated and Nonmediated Transport 308

Box 10-3 Biochemistry in Health and Disease The Action of Cardiac Glycosides 312

Part III Enzymes

11 Enzymatic Catalysis 322

1 General Properties of Enzymes 323

2 Activation Energy and the Reaction Coordinate 327

3 Catalytic Mechanisms 330

4 Lysozyme 339

5 Serine Proteases 345

Box 11-1 Perspectives in Biochemistry Drawing Reaction Mechanisms 331

Box 11-2 Perspectives in Biochemistry Effects of pH on Enzyme Activity 332

Box 11-3 Biochemistry in Health and Disease Nerve Poisons 346

Box 11-4 Biochemistry in Health and Disease the Blood Coagulation Cascade 356

12 Enzyme Kinetics, Inhibition, and Control 361

1 Reaction Kinetics 362

2 Enzyme Inhibition 374

3 Control of Enzyme Activity 382

4 Drug Design 391

Box 12-1 Pathways of Discovery J.B.S. Haldane and Enzyme Action 366

Box 12-2 Perspectives in Biochemistry Kinetics and Transition State Theory 369

Box 12-3 Biochemistry in Health and Disease HIV Enzyme Inhibitors 376

13 Biochemical Signaling 402

1 Hormones 403

2 Receptor Tyrosine Kinases 408

3 Heterotrimeric G Proteins 423

4 The Phosphoinositide Pathway 432

Box 13-1 Pathways of Discovery Rosalyn Yalow and the Radioimmunoassay (RIA) 404

Box 13-2 Perspectives in Biochemistry Receptor–Ligand Binding Can Be Quantitated 410

Box 13-3 Biochemistry in Health and Disease Oncogenes and Cancer 416

Box 13-4 Biochemistry in Health and Disease Drugs and Toxins That Affect Cell Signaling 431

Part IV Metabolism

14 Introduction to Metabolism 442

1 Overview of Metabolism 443

2 “High-Energy” Compounds 452

3 Oxidation–Reduction Reactions 462

4 Experimental Approaches to the Study of Metabolism 468

Box 14-1 Perspectives in Biochemistry Oxidation States of Carbon 447

Box 14-2 Pathways of Discovery Fritz Lipmann and “High-Energy” Compounds 453

Box 14-3 Perspectives in Biochemistry ATP and ΔG 455

15 Glucose Catabolism 478

1 Overview of Glycolysis 479

2 The Reactions of Glycolysis 481

3 Fermentation: The Anaerobic Fate of Pyruvate 497

4 Regulation of Glycolysis 502

5 Metabolism of Hexoses Other than Glucose 508

6 The Pentose Phosphate Pathway 512

Box 15-1 Pathways of Discovery Otto Warburg and Studies of Metabolism 479

Box 15-2 Perspectives in Biochemistry Synthesis of 2,3-Bisphosphoglycerate in Erythrocytes and Its Effect on the Oxygen Carrying Capacity of the Blood 494

Box 15-3 Perspectives in Biochemistry Glycolytic ATP Production in Muscle 502

Box 15-4 Biochemistry in Health and Disease Glucose-6-Phosphate Dehydrogenase Deficiency 518

16 Glycogen Metabolism and Gluconeogenesis 523

1 Glycogen Breakdown 524

2 Glycogen Synthesis 532

3 Control of Glycogen Metabolism 536

4 Gluconeogenesis 544

5 Other Carbohydrate Biosynthetic Pathways 551

Box 16-1 Pathways of Discovery Carl and Gerty Cori and Glucose Metabolism 526

Box 16-2 Biochemistry in Health and Disease Glycogen Storage Diseases 530

Box 16-3 Perspectives in Biochemistry Optimizing Glycogen Structure 537

Box 16-4 Perspectives in Biochemistry Lactose Synthesis 552

17 Citric Acid Cycle 558

1 Overview of the Citric Acid Cycle 559

2 Synthesis of Acetyl-Coenzyme A 562

3 Enzymes of the Citric Acid Cycle 568

4 Regulation of the Citric Acid Cycle 575

5 Reactions Related to the Citric Acid Cycle 579

Box 17-1 Pathways of Discovery Hans Krebs and the Citric Acid Cycle 561

Box 17-2 Biochemistry in Health and Disease Arsenic Poisoning 568

Box 17-3 Perspectives in Biochemistry Evolution of the Citric Acid Cycle 582

18 Electron Transport and Oxidative Phosphorylation 588

1 The Mitochondrion 589

2 Electron Transport 593

3 Oxidative Phosphorylation 609

4 Control of Oxidative Metabolism 620

Box 18-1 Perspectives in Biochemistry Cytochromes are Electron-Transport Heme Proteins 602

Box 18-2 Pathways of Discovery Peter Mitchell and the Chemiosmotic Theory 611

Box 18-3 Perspectives in Biochemistry Bacterial Electron Transport and Oxidative Phosphorylation 612

Box 18-4 Perspectives in Biochemistry Uncoupling in Brown Adipose Tissue Generates Heat 621

Box 18-5 Biochemistry in Health and Disease Oxygen Deprivation in Heart Attack and Stroke 625

19 Photosynthesis 630

1 Chloroplasts 631

2 The Light Reactions 635

3 The Dark Reactions 651

Box 19-1 Perspectives in Biochemistry Segregation of PSI and PSII 649

20 Lipid Metabolism 664

1 Lipid Digestion, Absorption, and Transport 664

2 Fatty Acid Oxidation 671

3 Ketone Bodies 685

4 Fatty Acid Biosynthesis 686

5 Regulation of Fatty Acid Metabolism 697

6 Synthesis of Other Lipids 700

7 Cholesterol Metabolism 706

Box 20-1 Biochemistry in Health and Disease Vitamin B12 Deficiency 680

Box 20-2 Pathways of Discovery Dorothy Crowfoot Hodgkin and the Structure of Vitamin B12 680

Box 20-3 Perspectives in Biochemistry Polyketide Synthesis 694

Box 20-4 Biochemistry in Health and Disease Sphingolipid Degradation and Lipid Storage Diseases 706

21 Amino Acid Metabolism 718

1 Protein Degradation 719

2 Amino Acid Deamination 724

3 The Urea Cycle 728

4 Breakdown of Amino Acids 733

5 Amino Acid Biosynthesis 746

6 Other Products of Amino Acid Metabolism 758

7 Nitrogen Fixation 764

Box 21-1 Biochemistry in Health and Disease Homocysteine, a Marker of Disease 740

Box 21-2 Biochemistry in Health and Disease Phenylketonuria and Alcaptonuria Result from Defects in Phenylalanine Degradation 746

Box 21-3 Biochemistry in Health and Disease the Porphyrias 760

22 Mammalian Fuel Metabolism: Integration and Regulation 773

1 Organ Specialization 774

2 Hormonal Control of Fuel Metabolism 781

3 Metabolic Homeostasis: The Regulation of Energy Metabolism, Appetite, and Body Weight 786

4 Disturbances in Fuel Metabolism 790

Box 22-1 Biochemistry in Health and Disease The Intestinal Microbiome 777

Box 22-2 Pathways of Discovery Frederick Banting and Charles Best and the Discovery of Insulin 794

Part V Gene Expression and Replication

23 Nucleotide Metabolism 802

1 Synthesis of Purine Ribonucleotides 802

2 Synthesis of Pyrimidine Ribonucleotides 809

3 Formation of Deoxyribonucleotides 812

4 Nucleotide Degradation 820

Box 23-1 Biochemistry in Health and Disease Inhibition of Thymidylate Synthesis in Cancer Therapy 821

Box 23-2 Pathways of Discovery Gertrude Elion and Purine Derivatives 826

24 Nucleic Acid Structure 831

1 The DNA Helix 832

2 Forces Stabilizing Nucleic Acid Structures 848

3 Fractionation of Nucleic Acids 856

4 DNA–Protein Interactions 859

5 Eukaryotic Chromosome Structure 868

Box 24-1 Pathways of Discovery Rosalind Franklin and the Structure of DNA 833

Box 24-2 Biochemistry in Health and Disease Inhibitors of Topoisomerases as Antibiotics and Anticancer Chemotherapeutic Agents 848

Box 24-3 Perspectives in Biochemistry The RNA World 854

25 DNA Replication, Repair, and Recombination 879

1 Overview of DNA Replication 880

2 Prokaryotic DNA Replication 882

3 Eukaryotic DNA Replication 898

4 DNA Damage 904

5 DNA Repair 909

6 Recombination 916

Box 25-1 Pathways of Discovery Arthur Kornberg and DNA Polymerase I 883

Box 25-2 Perspectives in Biochemistry Reverse Transcriptase 900

Box 25-3 Biochemistry in Health and Disease Telomerase, Aging, and Cancer 905

Box 25-4 Perspectives in Biochemistry DNA Methylation 908

Box 25-5 Perspectives in Biochemistry Why Doesn’t DNA Contain Uracil? 911

26 Transcription and RNA Processing 938

1 Prokaryotic RNA Transcription 939

2 Transcription in Eukaryotes 948

3 Posttranscriptional Processing 961

Box 26-1 Perspectives in Biochemistry Collisions between DNA Polymerase and RNA Polymerase 945

Box 26-2 Biochemistry in Health and Disease Inhibitors of Transcription 950

Box 26-3 Pathways of Discovery Richard Roberts and Phillip Sharp and the Discovery of Introns 964

27 Protein Synthesis 982

1 The Genetic Code 983

2 Transfer RNA and Its Aminoacylation 988

3 Ribosomes 996

4 Translation 1004

5 Posttranslational Processing 1024

Box 27-1 Perspectives in Biochemistry Evolution of the Genetic Code 986

Box 27-2 Perspectives in Biochemistry Expanding the Genetic Code 996

Box 27-3 Biochemistry in Health and Disease the Effects of Antibiotics on Protein Synthesis 1020

28 Regulation of Gene Expression 1033

1 Genome Organization 1034

2 Regulation of Prokaryotic Gene Expression 1043

3 Regulation of Eukaryotic Gene Expression 1052

4 The Cell Cycle, Cancer, Apoptosis, and Development 1080

Box 28-1 Biochemistry in Health and Disease Trinucleotide Repeat Diseases 1040

Box 28-2 Perspectives in Biochemistry X Chromosome Inactivation 1053

Box 28-3 Perspectives in Biochemistry Nonsense-Mediated Decay 1070

Glossary G-1

Index I-1

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