Essential Biochemistry

Charlott Pratt received her Ph.D. in biochemistry from Duke University. She did post-doctoral research at the University of North Carolina at Chapel Hill and has contributed to numerous primary research articles and reviews. She is presently in the Department of Chemistry at Seattle Pacific University. She is co-author with Donald Voet and Judith Voet of Fundamentals of Biochemistry, also published by Wiley. Kathleen Cornely received her Ph.D. in biochemistry from Cornell University. She has published numerous research articles and is presently Professor in the Department of Chemistry and Biochemistry at Providence College. She is a member of the Educational and Professional Development Committee of the American Society for Biochemistry and Molecular Biology and is on the editorial borad for the journal, Biochemistry and Molecular Biology Education.

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