Biochemistry (Sixth edition)

Front Cover......Page 1
Title Page......Page 5
Copyright......Page 6
Brief Contents......Page 9
Contents......Page 10
1.1 Basic Themes......Page 23
1.2 Chemical Foundations of Biochemistry......Page 25
The Earth and Its Age......Page 27
Biochemical Connections: Why Structural Formulas Are So Important......Page 28
Biomolecules......Page 29
Molecules to Cells......Page 33
1.4 The Biggest Biological Distinction—Prokaryotes and Eukaryotes......Page 36
1.6 Eukaryotic Cells......Page 38
1.7 Five Kingdoms, Three Domains......Page 44
1.8 Common Ground for All Cells......Page 47
1.9 Biochemical Energetics......Page 49
1.10 Energy and Change......Page 51
1.11 Spontaneity in Biochemical Reactions......Page 52
1.12 Life and Thermodynamics......Page 53
Biochemical Connections: Predicting Reactions......Page 54
Summary......Page 55
Review Exercises......Page 56
Annotated Bibliography......Page 58
2.1 Water and Polarity......Page 59
Solvent Properties of Water......Page 60
2.2 Hydrogen Bonds......Page 64
Other Biologically Important Hydrogen Bonds......Page 67
Biochemical Connections: How Basic Chemistry Affects Life: The Importance of the Hydrogen Bond......Page 68
2.3 Acids, Bases, and pH......Page 69
2.4 Titration Curves......Page 73
2.5 Buffers......Page 75
Biochemical Connections: Buffer Selection......Page 81
Biochemical Connections: Some Physiological Consequences of Blood Buffering......Page 82
Summary......Page 83
Review Exercises......Page 84
Annotated Bibliography......Page 86
3.1 Amino Acids Exist in a Three-Dimensional World......Page 87
3.2 Individual Amino Acids: Their Structures and Properties......Page 88
Uncommon Amino Acids......Page 92
Biochemical Connections: Amino Acids to Calm Down and Pep Up......Page 94
3.3 Amino Acids Can Act as Both Acids and Bases......Page 95
3.4 The Peptide Bond......Page 99
Biochemical Connections: Amino Acids Go Many Different Places......Page 101
Biochemical Connections: Aspartame, the Sweet Peptide......Page 102
Biochemical Connections: Phenylketonuria—Little Molecules Have Big Effects......Page 104
Biochemical Connections: Peptide Hormones—More Small Molecules with Big Effects......Page 105
Review Exercises......Page 106
Annotated Bibliography......Page 108
4.1 Protein Structure and Function......Page 109
4.2 Primary Structure of Proteins......Page 110
Periodic Structures in Protein Backbones......Page 111
Biochemical Connections: Complete Proteins and Nutrition......Page 112
The Collagen Triple Helix......Page 115
Two Types of Protein Conformations: Fibrous and Globular......Page 119
4.4 Tertiary Structure of Proteins......Page 120
Forces Involved in Tertiary Structures......Page 121
Myoglobin: An Example of Protein Structure......Page 124
Denaturation and Refolding......Page 126
Hemoglobin......Page 128
Conformational Changes That Accompany Hemoglobin Function......Page 130
4.6 Protein Folding Dynamics......Page 134
Hydrophobic Interactions: A Case Study in Thermodynamics......Page 136
Protein-Folding Chaperones......Page 138
Biochemical Connections: Prions and Disease......Page 140
Summary......Page 141
Review Exercises......Page 142
Annotated Bibliography......Page 143
5.1 Extracting Pure Proteins from Cells......Page 145
5.2 Column Chromatography......Page 146
5.3 Electrophoresis......Page 151
5.4 Determining the Primary Structure of a Protein......Page 154
Cleavage of the Protein into Peptides......Page 155
Sequencing of Peptides: The Edman Method......Page 156
Summary......Page 161
Review Exercises......Page 162
Annotated Bibliography......Page 164
6.2 Kinetics versus Thermodynamics......Page 165
Biochemical Connections: Enzymes as Markers for Disease......Page 167
6.3 Enzyme Kinetic Equations......Page 168
6.4 Enzyme–Substrate Binding......Page 170
6.5 Examples of Enzyme-Catalyzed Reactions......Page 172
6.6 The Michaelis–Menten Approach to Enzyme Kinetics......Page 174
6.7 Enzyme Inhibition......Page 181
Biochemical Connections: Practical Information from Kinetic Data......Page 182
Biochemical Connections: Enzyme Inhibition in the Treatment of AIDS......Page 187
Review Exercises......Page 188
Annotated Bibliography......Page 191
7.1 The Behavior of Allosteric Enzymes......Page 193
7.2 The Concerted and Sequential Models for Allosteric Enzymes......Page 197
7.3 Control of Enzyme Activity by Phosphorylation......Page 201
7.4 Zymogens......Page 204
7.5 The Nature of the Active Site......Page 205
7.6 Chemical Reactions Involved in Enzyme Mechanisms......Page 210
Biochemical Connections: Enzymes Catalyze Familiar Reactions of Organic Chemistry......Page 212
7.7 The Active Site and Transition States......Page 214
Biochemical Connections: Families of Enzymes: Proteases......Page 215
7.8 Coenzymes......Page 216
Biochemical Connections: Catalytic Antibodies against Cocaine......Page 218
Summary......Page 220
Review Exercises......Page 221
Annotated Bibliography......Page 222
8.2 The Chemical Natures of the Lipid Types......Page 223
8.3 Biological Membranes......Page 230
Biochemical Connections: Butter versus Margarine—Which Is Healthier?......Page 234
8.4 The Kinds of Membrane Proteins......Page 235
8.5 The Fluid-Mosaic Model of Membrane Structure......Page 237
8.6 The Functions of Membranes......Page 238
Biochemical Connections: Lipid Droplets Are Not Just Great Balls of Fat......Page 243
Vitamin D......Page 244
Biochemical Connections: Vision Has Great Chemistry......Page 247
Vitamin K......Page 248
8.8 Prostaglandins and Leukotrienes......Page 250
Biochemical Connections: Why Should We Eat More Salmon?......Page 252
Summary......Page 253
Review Exercises......Page 254
Annotated Bibliography......Page 255
9.2 The Covalent Structure of Polynucleotides......Page 257
Biochemical Connections: The DNA Family Tree......Page 262
9.3 The Structure of DNA......Page 263
Biochemical Connections: What Makes a Triple Helix Useful in Drug Design?......Page 269
9.4 Denaturation of DNA......Page 271
9.5 The Principal Kinds of RNA and Their Structures......Page 272
Biochemical Connections: The Human Genome Project: Treasure or Pandora’s Box?......Page 273
Biochemical Connections: Why Identical Twins Are Not Identical......Page 279
Summary......Page 280
Review Exercises......Page 281
Annotated Bibliography......Page 282
10.1 The Flow of Genetic Information in the Cell......Page 283
Semiconservative Replication......Page 284
Semidiscontinuous DNA Replication......Page 287
DNA Polymerase from E. coli......Page 289
Supercoiling and Replication......Page 292
The Primase Reaction......Page 293
Synthesis and Linking of New DNA Strands......Page 294
10.5 Proofreading and Repair......Page 295
Biochemical Connections: Why Does DNA Contain Thymine and Not Uracil?......Page 298
10.6 Eukaryotic DNA Replication......Page 300
Biochemical Connections: The SOS Response in E. coli......Page 301
Eukaryotic DNA Polymerases......Page 303
The Eukaryotic Replication Fork......Page 304
Review Exercises......Page 307
Annotated Bibliography......Page 308
11.1 Overview of Transcription......Page 309
RNA Polymerase in Escherichia coli......Page 310
Promoter Structure......Page 311
Chain Initiation......Page 312
Chain Elongation......Page 313
Chain Termination......Page 315
Enhancers......Page 317
Operons......Page 318
Transcription Attenuation......Page 322
11.4 Transcription in Eukaryotes......Page 325
Structure of RNA Polymerase II......Page 326
Pol II Promoters......Page 327
Initiation of Transcription......Page 328
Elongation and Termination......Page 329
Enhancers and Silencers......Page 331
Biochemical Connections: TFIIH—Making the Most Out of the Genome......Page 332
Response Elements......Page 333
RNA Interference......Page 336
Helix–Turn–Helix Motifs......Page 337
Basic-Region Leucine Zipper Motif......Page 339
Transcription-Activation Domains......Page 340
Messenger RNA......Page 341
The Splicing Reaction: Lariats and Snurps......Page 344
Biochemical Connections: Lupus: An Autoimmune Disease Involving RNA Processing......Page 345
11.8 Ribozymes......Page 346
Biochemical Connections: Proofreading in Transcription? RNA Fills In Another Missing Piece......Page 348
Summary......Page 349
Review Exercises......Page 350
Annotated Bibliography......Page 351
12.1 Translating the Genetic Message......Page 353
12.2 The Genetic Code......Page 354
Codon–Anticodon Pairing and Wobble......Page 356
12.3 Amino Acid Activation......Page 360
Ribosomal Architecture......Page 362
Chain Initiation......Page 363
Chain Elongation......Page 365
Chain Termination......Page 367
The Ribosome Is a Ribozyme......Page 368
Biochemical Connections: The 21st Amino Acid?......Page 370
Polysomes......Page 371
Chain Initiation......Page 373
Chain Termination......Page 375
12.6 Posttranslational Modification of Proteins......Page 376
12.7 Protein Degradation......Page 377
Biochemical Connections: Chaperones: Preventing Unsuitable Associations......Page 378
Biochemical Connections: Silent Mutations Are Not Always Silent......Page 379
Biochemical Connections: How Do We Adapt to High Altitude?......Page 381
Review Exercises......Page 382
Annotated Bibliography......Page 384
Separation Techniques......Page 385
Detection Methods......Page 386
13.2 Restriction Endonucleases......Page 387
Many Restriction Endonucleases Produce “Sticky Ends”......Page 388
Using “Sticky Ends” to Construct Recombinant DNA......Page 390
13.4 Genetic Engineering......Page 397
Bacteria as “Protein Factories”......Page 398
Biochemical Connections: Genetic Engineering in Agriculture......Page 399
Protein Expression Vectors......Page 400
Genetic Engineering in Eukaryotes......Page 401
Biochemical Connections: Human Proteins through Genetic Recombination Techniques......Page 403
13.5 DNA Libraries......Page 404
Biochemical Connections: Fusion Proteins and Fast Purifications......Page 405
Finding an Individual Clone in a DNA Library......Page 406
13.6 The Polymerase Chain Reaction......Page 408
13.7 DNA Fingerprinting......Page 410
Biochemical Connections: CSI: Biochemistry—Forensic Uses of DNA Testing......Page 411
Restriction-Fragment Length Polymorphisms: A Powerful Method for Forensic Analysis......Page 413
13.8 Sequencing DNA......Page 415
Biochemical Connections: RNA Interference—The Newest Way to Study Genes......Page 416
13.9 Genomics and Proteomics......Page 418
The Power of Microarrays—Robotic Technology Meets Biochemistry......Page 419
Protein Arrays......Page 420
Summary......Page 422
Review Exercises......Page 423
Annotated Bibliography......Page 425
Families of Viruses......Page 427
Virus Life Cycles......Page 428
14.2 Retroviruses......Page 432
14.3 The Immune System......Page 434
Innate Immunity—The Front Lines of Defense......Page 436
T-Cell Functions......Page 438
T-Cell Memory......Page 441
The Immune System: Molecular Aspects......Page 443
Distinguishing Self from Nonself......Page 444
Biochemical Connections: Viral RNAs Outwit the Immune System......Page 446
14.4 Cancer......Page 447
Oncogenes......Page 449
Tumor Suppressors......Page 451
Viruses and Cancer......Page 452
Viruses Helping Cure Cancer......Page 453
Biochemical Connections: Attacking the Symptoms instead of the Disease?......Page 456
Summary......Page 457
Review Exercises......Page 458
Annotated Bibliography......Page 459
15.1 Standard States for Free-Energy Changes......Page 461
15.2 A Modified Standard State for Biochemical Applications......Page 462
Biochemical Connections: Living Things Need Energy—How Do They Use It?......Page 463
15.3 The Nature of Metabolism......Page 464
Biochemical Connections: Living Things Are Unique Thermodynamic Systems......Page 465
15.4 The Role of Oxidation and Reduction in Metabolism......Page 466
15.5 Coenzymes in Biologically Important Oxidation–Reduction Reactions......Page 467
15.6 Coupling of Production and Use of Energy......Page 470
15.7 Coenzyme A in Activation of Metabolic Pathways......Page 475
Review Exercises......Page 479
Annotated Bibliography......Page 482
16.1 Sugars: Their Structures and Stereochemistry......Page 483
16.2 Reactions of Monosaccharides......Page 491
Biochemical Connections: Vitamin C Is Related to Sugars......Page 493
16.3 Some Important Oligosaccharides......Page 497
Biochemical Connections: Fruits, Flowers, Striking Colors, and Medicinal Uses Too......Page 498
16.4 Structures and Functions of Polysaccharides......Page 500
Biochemical Connections: Why Is Dietary Fiber So Good for You?......Page 505
16.5 Glycoproteins......Page 508
Summary......Page 510
Review Exercises......Page 511
Annotated Bibliography......Page 513
17.1 The Overall Pathway of Glycolysis......Page 515
Biochemical Connections: Biofuels from Fermentation......Page 518
17.2 Conversion of Six-Carbon Glucose to Three-Carbon Glyceraldehyde-3-Phosphate......Page 519
17.3 Glyceraldehyde-3-Phosphate Is Converted to Pyruvate......Page 524
17.4 Anaerobic Metabolism of Pyruvate......Page 532
Biochemical Connections: What Is the Connection between Anaerobic Metabolism and Dental Plaque?......Page 535
Biochemical Connections: Fetal Alcohol Syndrome......Page 536
17.5 Energy Production in Glycolysis......Page 537
Summary......Page 538
Review Exercises......Page 539
Annotated Bibliography......Page 540
18.1 How Glycogen Is Produced and Degraded......Page 541
Biochemical Connections: Why Do Athletes Go In for Glycogen Loading?......Page 548
18.2 Gluconeogenesis Produces Glucose from Pyruvate......Page 549
18.3 Control of Carbohydrate Metabolism......Page 553
18.4 Glucose Is Sometimes Diverted through the Pentose Phosphate Pathway......Page 558
Biochemical Connections: The Pentose Phosphate Pathway and Hemolytic Anemia......Page 562
Summary......Page 563
Review Exercises......Page 564
Annotated Bibliography......Page 565
19.1 The Central Role of the Citric Acid Cycle in Metabolism......Page 567
19.2 The Overall Pathway of the Citric Acid Cycle......Page 568
19.3 How Pyruvate Is Converted to Acetyl-CoA......Page 571
19.4 The Individual Reactions of the Citric Acid Cycle......Page 574
Biochemical Connections: Plant Poisons and the Citric Acid Cycle......Page 577
19.5 Energetics and Control of the Citric Acid Cycle......Page 582
19.6 The Glyoxylate Cycle: A Related Pathway......Page 584
19.7 The Citric Acid Cycle in Catabolism......Page 586
19.8 The Citric Acid Cycle in Anabolism......Page 587
Biochemical Connections: Why Can’t Animals Use All the Same Energy Sources as Plants and Bacteria?......Page 591
Summary......Page 593
Biochemical Connections: Why Is It So Hard to Lose Weight?......Page 594
Review Exercises......Page 596
Annotated Bibliography......Page 597
20.1 The Role of Electron Transport in Metabolism......Page 599
20.2 Reduction Potentials in the Electron Transport Chain......Page 600
20.3 Organization of Electron Transport Complexes......Page 603
20.4 The Connection between Electron Transport and Phosphorylation......Page 610
20.5 The Mechanism of Coupling in Oxidative Phosphorylation......Page 613
20.6 Respiratory Inhibitors Can Be Used to Study Electron Transport......Page 616
Biochemical Connections: What Does Brown Adipose Tissue Have to Do with Obesity?......Page 619
20.8 The ATP Yield from Complete Oxidation of Glucose......Page 621
Biochemical Connections: Sports and Metabolism......Page 622
Summary......Page 623
Biochemical Connections: The Darker Side of Sports......Page 624
Review Exercises......Page 626
Annotated Bibliography......Page 628
21.2 Catabolism of Lipids......Page 629
21.3 The Energy Yield from the Oxidation of Fatty Acids......Page 634
21.4 Catabolism of Unsaturated Fatty Acids and Odd-Carbon Fatty Acids......Page 636
21.5 Ketone Bodies......Page 638
21.6 Fatty-Acid Biosynthesis......Page 640
Biochemical Connections: Ketone Bodies and Effective Weight Loss......Page 641
Biochemical Connections: A Gene for Obesity......Page 648
Triacylglycerols......Page 649
Biochemical Connections: Acetyl-CoA Carboxylase—A New Target in the Fight against Obesity?......Page 650
21.8 Cholesterol Biosynthesis......Page 653
Biochemical Connections: Atherosclerosis......Page 662
Summary......Page 663
Review Exercises......Page 664
Annotated Bibliography......Page 666
22.1 Chloroplasts Are the Site of Photosynthesis......Page 667
22.2 Photosystems I and II and the Light Reactions of Photosynthesis......Page 671
Cyclic Electron Transport in Photosystem I......Page 675
22.3 Photosynthesis and ATP Production......Page 678
22.4 Evolutionary Implications of Photosynthesis with and without Oxygen......Page 680
22.5 Dark Reactions of Photosynthesis Fix CO[sup(2)]......Page 682
Biochemical Connections: Chloroplast Genes......Page 686
Summary......Page 690
Review Exercises......Page 691
Annotated Bibliography......Page 692
23.1 Nitrogen Metabolism: An Overview......Page 693
23.2 Nitrogen Fixation......Page 694
Biochemical Connections: Why Is the Nitrogen Content of Fertilizers So Important?......Page 695
23.3 Feedback Inhibition in Nitrogen Metabolism......Page 696
23.4 Amino Acid Biosynthesis......Page 698
23.6 Amino Acid Catabolism......Page 707
Excretion of Excess Nitrogen......Page 708
Biochemical Connections: Water and the Disposal of Nitrogen Wastes......Page 709
Anabolism of Inosine Monophosphate......Page 713
23.8 Purine Catabolism......Page 716
Biochemical Connections: Lesch–Nyhan Syndrome......Page 718
The Anabolism of Pyrimidine Nucleotides......Page 719
23.10 Conversion of Ribonucleotides to Deoxyribonucleotides......Page 722
23.11 Conversion of dUTP to dTTP......Page 723
Summary......Page 725
Review Exercises......Page 726
Annotated Bibliography......Page 727
24.1 Connections between Metabolic Pathways......Page 729
24.2 Biochemistry and Nutrition......Page 730
Biochemical Connections: Alcohol Consumption and Addiction......Page 731
The Food Pyramid......Page 734
Hormones......Page 738
Cyclic AMP and G Proteins......Page 742
Calcium Ion as a Second Messenger......Page 744
Receptor Tyrosine Kinases......Page 746
24.4 Hormones and the Control of Metabolism......Page 747
24.5 Insulin and Its Effects......Page 750
Insulin’s Effect on Glucose Uptake......Page 751
Insulin Affects Many Enzymes......Page 752
Insulin and Sports......Page 753
Biochemical Connections: A Workout a Day Keeps Diabetes Away?......Page 754
Biochemical Connections: The Search for Longevity......Page 755
Review Exercises......Page 756
Annotated Bibliography......Page 758
Doping in Sports: Good Science Gone Bad......Page 759
Bird Flu: The Next Pandemic?......Page 762
Single Nucleotide Polymorphisms: Changing One Base Can Make a Big Difference......Page 764
HPV Vaccines: Waging the War on Cervical Cancer......Page 767
Stem Cells: Hope or Hype?......Page 769
Biochemistry: Hide and Seek: Finding a Cure for HIV......Page 771
Glossary......Page 774
Answers to Questions......Page 780
Index......Page 823