Biochemistry

Front Cover......Page 1
Title Page......Page 2
Copyright......Page 3
Table of Contents......Page 7
1.1 What Are the Basic Themes for This Text?......Page 26
1.2 What Is the Chemical Nature of Important Biomolecules?......Page 27
The Earth and Its Age......Page 30
Biomolecules......Page 32
Biochemical Connections: Structure and Function of Biomolecules......Page 33
Molecules to Cells......Page 35
1.4 How Do Prokaryotes and Eukaryotes Differ in Levels of Organization?......Page 39
1.5 What Are the Main Structural Features of Prokaryotic Cells?......Page 40
Important Organelles......Page 41
Other Organelles and Cellular Constituents......Page 44
1.7 How Do We Classify Organisms: Five Kingdoms or Three Domains?......Page 46
Biochemical Connections: Extremophiles: The Toast of the Biotechnology Industry......Page 48
1.8 Is There Common Ground for All Cells?......Page 49
1.9 How Do Cells Use Energy?......Page 51
1.10 What Is the Connection between Energy and Change?......Page 52
1.12 What Is the Connection between Thermodynamics and Life?......Page 53
Biochemical Connections: Entropy and Probability......Page 54
Critical Questions to Review......Page 55
Annotated Bibliography......Page 58
2.1 What Makes Water a Polar Molecule?......Page 59
Solvent Properties of Water......Page 60
2.2 What Is a Hydrogen Bond?......Page 63
Biologically Important Hydrogen Bonds Other Than to Water Molecules......Page 66
2.3 What Are Acids and Bases?......Page 67
2.4 What Is pH, and What Does It Have to Do with the Properties of Water?......Page 68
Monitoring Acidity......Page 69
2.5 What Are Titration Curves?......Page 71
2.6 What Are Buffers, and Why Are They Important?......Page 73
Biochemical Connections: Buffer Selection......Page 77
Buffer Systems of Physiological Importance......Page 78
Biochemical Connections: Some Physiological Consequences of Blood Buffering......Page 79
Critical Questions to Review......Page 80
Annotated Bibliography......Page 82
3.1 What Are Amino Acids, and What Is Their Three-Dimensional Structure?......Page 83
Group 1—Amino Acids with Nonpolar Side Chains......Page 84
Group 2—Amino Acids with Electrically Neutral Polar Side Chains......Page 87
Group 4—Amino Acids with Basic Side Chains......Page 88
Biochemical Connections: Amino Acids and Neurotransmitters......Page 89
3.3 Do Amino Acids Have Specific Acid–Base Properties?......Page 90
3.4 What Is the Peptide Bond?......Page 93
Biochemical Connections: Amino Acid Functions Other Than in Peptides......Page 95
3.5 Are Small Peptides Physiologically Active?......Page 97
Biochemical Connections: Aspartame, the Sweet Peptide......Page 98
Biochemical Connections: Phenylketonuria and Inborn Errors of Metabolism......Page 100
Biochemical Connections: Peptide Hormones......Page 101
Critical Questions to Review......Page 102
Annotated Bibliography......Page 103
Levels of Structure in Proteins......Page 105
4.3 What Is the Secondary Structure of Proteins?......Page 106
Biochemical Connections: Complete Proteins and Nutrition......Page 107
The α-Helix......Page 108
Irregularities in Regular Structures......Page 110
Supersecondary Structures and Domains......Page 111
The Collagen Triple Helix......Page 115
Two Types of Protein Conformations: Fibrous and Globular......Page 116
4.4 What Can We Say about the Thermodynamics of Protein Folding?......Page 117
Hydrophobic Interactions: A Case Study in Thermodynamics......Page 118
4.5 What Is the Tertiary Structure of Proteins?......Page 120
Myoglobin: An Example of Protein Structure......Page 122
Denaturation and Refolding......Page 124
4.6 Can We Predict Protein Folding from Sequence?......Page 126
Protein-Folding Chaperones......Page 127
Biochemical Connections: Prions......Page 128
Hemoglobin......Page 129
Conformational Changes That Accompany Hemoglobin Function......Page 130
Critical Questions to Review......Page 135
Annotated Bibliography......Page 137
Isolation of Proteins from Cells......Page 138
5.2 What Is Column Chromatography?......Page 141
5.3 What Is Electrophoresis?......Page 146
5.4 How Do We Determine the Primary Structure of a Protein?......Page 147
Cleavage of the Protein into Peptides......Page 149
Sequencing of Peptides: The Edman Method......Page 151
Critical Questions to Review......Page 153
Annotated Bibliography......Page 155
6.2 What Is the Difference between the Kinetic and the Thermodynamic Aspects of Reactions?......Page 156
Biochemical Connections: Enzymes as Markers for Disease......Page 158
6.3 How Can We Describe Enzyme Kinetics in Mathematical Terms?......Page 159
6.4 How Do Substrates Bind to Enzymes?......Page 160
6.5 What Are Some Examples of Enzyme-Catalyzed Reactions?......Page 162
6.6 What Is the Michaelis–Menten Approach to Enzyme Kinetics?......Page 164
Linearizing the Michaelis–Menten Equation......Page 167
Significance of K[sub(M)] and V[sub(max)]......Page 169
Kinetics of Competitive Inhibition......Page 171
Biochemical Connections: Practical Information from Kinetic Data......Page 172
Kinetics of Noncompetitive Inhibition......Page 174
Biochemical Connections: Enzyme Inhibition in the Treatment of AIDS......Page 176
Critical Questions to Review......Page 177
Annotated Bibliography......Page 179
7.1 Does the Michaelis–Menten Model Describe the Behavior of Allosteric Enzymes?......Page 181
Control Mechanisms That Affect Allosteric Enzymes......Page 182
The Concerted Model for Allosteric Behavior......Page 185
The Sequential Model for Allosteric Behavior......Page 188
7.3 How Does Phosphorylation of Specific Residues Regulate Enzyme Activity?......Page 189
7.4 What Are Zymogens, and How Do They Control Enzyme Activity?......Page 191
7.5 How Do Active-Site Events of an Enzyme Affect the Reaction Mechanism?......Page 192
Determining the Essential Amino Acid Residues......Page 193
The Architecture of the Active Site......Page 194
The Mechanism of Chymotrypsin Action......Page 195
7.6 What Types of Chemical Reactions Are Involved in Enzyme Mechanisms?......Page 197
Biochemical Connections: Enzymes Catalyze Familiar Reactions of Organic Chemistry......Page 198
7.7 What Is the Connection between the Active Site and Transition States?......Page 201
7.8 What Are Coenzymes?......Page 203
Biochemical Connections: Catalytic Antibodies against Cocaine......Page 204
Critical Questions to Review......Page 206
Annotated Bibliography......Page 208
Fatty Acids......Page 209
Triacylglycerols......Page 211
Phosphoacylglycerols (Phospholipids)......Page 212
Steroids......Page 214
Biochemical Connections: Myelin and Multiple Sclerosis......Page 215
8.3 What Is the Nature of Biological Membranes?......Page 216
Lipid Bilayers......Page 217
Biochemical Connections: Butter Versus Margarine—Which Is Healthier?......Page 220
8.4 What Are Some Common Types of Membrane Proteins?......Page 221
8.5 What Is the Fluid-Mosaic Model of Membrane Structure?......Page 222
Biochemical Connections: Membranes in Medicine......Page 223
Membrane Transport......Page 224
Membrane Receptors......Page 227
Vitamin A......Page 228
Vitamin D......Page 230
Vitamin E......Page 231
Biochemical Connections: The Chemistry of Vision......Page 232
Vitamin K......Page 233
8.8 What Are Prostaglandins and Leukotrienes, and What Do They Have to Do with Lipids?......Page 234
Summary......Page 237
Critical Questions to Review......Page 238
Annotated Bibliography......Page 239
9.1 What Are the Levels of Structure in Nucleic Acids?......Page 240
9.2 What Is the Covalent Structure of Polynucleotides?......Page 241
Secondary Structure of DNA: The Double Helix......Page 245
Conformational Variations in DNA......Page 247
Tertiary Structure of DNA: Supercoiling......Page 250
Supercoiling in Prokaryotic DNA......Page 251
9.4 How Does the Denaturation of DNA Take Place?......Page 253
Biochemical Connections: The Human Genome Project: Prospects and Possibilities......Page 255
9.5 What Are the Principal Kinds of RNA and Their Structures?......Page 256
Transfer RNA......Page 258
Ribosomal RNA......Page 259
Small Nuclear RNA......Page 261
Critical Questions to Review......Page 262
Annotated Bibliography......Page 264
10.1 What Is the Flow of Genetic Information in the Cell?......Page 265
10.2 What Are the General Considerations in the Replication of DNA?......Page 266
Semiconservative Replication......Page 267
Bidirectional Replication......Page 268
DNA Polymerase from E. coli......Page 269
The Primase Reaction......Page 273
Synthesis and Linking of New DNA Strands......Page 274
10.5 How Do Proofreading and Repair Take Place?......Page 275
Biochemical Connections: Why Does DNA Contain Thymine and Not Uracil?......Page 276
10.6 How Is DNA Replicated in Eukaryotes?......Page 280
Eukaryotic DNA Polymerases......Page 281
Biochemical Connections: Telomerase and Cancer......Page 283
The Eukaryotic Replication Fork......Page 285
Summary......Page 286
Critical Questions to Review......Page 287
Annotated Bibliography......Page 288
RNA Polymerase in Escherichia coli......Page 289
Promoter Structure......Page 291
Chain Elongation......Page 292
Chain Termination......Page 293
Alternative σ Factors......Page 295
Enhancers......Page 296
Operons......Page 297
Transcription Attenuation......Page 300
Structure of RNA Polymerase II......Page 303
Pol II Promoters......Page 304
Initiation of Transcription......Page 305
11.4 How Is Transcription Regulated in Eukaryotes?......Page 308
Biochemical Connections: TFIIH—Making the Most Out of the Genome......Page 309
Response Elements......Page 310
Helix–Turn–Helix Motifs......Page 313
Basic-Region Leucine Zipper Motif......Page 315
Transfer RNA and Ribosomal RNA......Page 316
Messenger RNA......Page 318
The Splicing Reaction: Lariats and Snurps......Page 319
Alternative RNA Splicing......Page 321
11.7 How Does RNA Act as an Enzyme?......Page 322
Critical Questions to Review......Page 323
Annotated Bibliography......Page 324
12.1 What Is the Overall Process of Translating the Genetic Message?......Page 326
12.2 What Is the Genetic Code?......Page 327
Codon–Anticodon Pairing and Wobble......Page 329
12.3 What Is the Role of Aminoacyl-tRNA Synthetases in Amino Acid Activation?......Page 332
Chain Initiation......Page 334
Chain Elongation......Page 336
Chain Termination......Page 340
Biochemical Connections: The 21st Amino Acid?......Page 342
Polysomes......Page 343
Chain Initiation......Page 345
Chain Elongation......Page 346
Chain Termination......Page 347
12.6 How Does Posttranslational Modification of Proteins Take Place?......Page 348
Biochemical Connections: Molecular Chaperones: Preventing Unsuitable Associations......Page 349
12.7 How Are Proteins Degraded?......Page 350
Biochemical Connections: How Do We Adapt to High Altitude?......Page 351
Summary......Page 352
Critical Questions to Review......Page 353
Annotated Bibliography......Page 354
Separation Techniques......Page 355
Detection Methods......Page 356
13.2 What Makes Restriction Endonucleases an Important Tool for DNA Research?......Page 357
Many Restriction Endonucleases Produce "Sticky Ends"......Page 358
Using "Sticky Ends" to Construct Recombinant DNA......Page 359
Biochemical Connections: Restriction Endonucleases: "Molecular Scissors"......Page 360
DNA Recombination Occurs in Nature......Page 367
Biochemical Connections: Genetic Engineering in Agriculture......Page 368
Bacteria as "Protein Factories"......Page 369
Protein Expression Vectors......Page 370
Genetic Engineering in Eukaryotes......Page 372
Biochemical Connections: Fusion Proteins and Fast Purifications......Page 373
13.5 What Are DNA Libraries?......Page 374
Finding an Individual Clone in a DNA Library......Page 376
13.6 What Is the Polymerase Chain Reaction?......Page 377
Biochemical Connections: Forensic Uses of DNA Testing......Page 379
13.7 What Is Site-Directed Mutagenesis?......Page 380
13.8 What Is DNA Fingerprinting?......Page 382
Restriction-Fragment Length Polymorphisms: A Powerful Method for Forensic Analysis......Page 383
13.9 How Can We Study DNA-Protein Interactions?......Page 384
13.10 What Are Some Methods for Studying Transcription?......Page 386
Biochemical Connections: DNA Chips—Robotic Technology Meets Biochemistry......Page 388
Biochemical Connections: RNA Interference—The Newest Way to Study Genes......Page 389
13.11 How Do We Determine the Base Sequences of Nucleic Acids?......Page 390
13.12 How Can We Use Bioinformatics to Study Genomics and Proteomics?......Page 391
Critical Questions to Review......Page 394
Annotated Bibliography......Page 396
14.1 What Are Viruses?......Page 397
Families of Viruses......Page 398
Virus Life Cycles......Page 399
Biochemical Connections: Influenza—The Virus That Won't Go Away......Page 403
14.2 What Virus Causes Severe Acute Respiratory Syndrome (SARS)?......Page 404
14.3 What Is Unique about Retroviruses?......Page 405
14.4 How Are Viruses Used in Gene Therapy?......Page 406
14.5 How Does the Immune System Defend the Body?......Page 409
Innate Immunity—The Front Lines of Defense......Page 410
T-Cell Functions......Page 412
T-Cell Memory......Page 415
The Immune System: Molecular Aspects......Page 416
Biochemical Connections: A Carbohydrate-Based Anticancer Vaccine......Page 418
Distinguishing Self from Nonself......Page 419
14.6 How Does Human Immunodeficiency Virus Cause AIDS?......Page 421
The Search for a Vaccine......Page 423
Antibodies Get a Second Chance......Page 425
History of Stem-Cell Research......Page 426
Stem Cells Offer Hope......Page 427
The Mark of a Cancer Cell......Page 428
Oncogenes......Page 429
Tumor Suppressors......Page 431
Biochemical Connections: If It Isn't One Thing, It's Another......Page 432
Biochemical Connections: Viruses Helping Cure Cancer......Page 433
Summary......Page 435
Critical Questions to Review......Page 436
Annotated Bibliography......Page 437
15.1 What Are Standard States for Free-Energy Changes?......Page 439
15.2 What Is a Modified Standard State for Biochemical Applications?......Page 440
Biochemical Connections: Biochemical Thermodynamics......Page 441
15.3 What Is Metabolism?......Page 442
15.4 How Are Oxidation and Reduction Involved in Metabolism?......Page 443
15.5 How Are Coenzymes Used in Biologically Important Oxidation–Reduction Reactions?......Page 445
15.6 How Are Production and Use of Energy Coupled?......Page 447
15.7 How Is Coenzyme A Involved in Activation of Metabolic Pathways?......Page 452
Summary......Page 455
Critical Questions to Review......Page 456
Annotated Bibliography......Page 458
16.1 What Are the Structures and the Stereochemistry of Monosaccharides?......Page 459
Cyclic Structures: Anomers......Page 462
Oxidation–Reduction Reactions......Page 465
Esterification Reactions......Page 467
The Formation of Glycosides......Page 468
Other Derivatives of Sugars......Page 471
Biochemical Connections: Glycosides, Fruits, and Flowers......Page 472
16.3 What Are Some Important Oligosaccharides?......Page 473
16.4 What Are the Structures and Functions of Polysaccharides?......Page 474
Biochemical Connections: Lactose Intolerance......Page 475
The Forms of Starch......Page 476
Glycogen......Page 478
Biochemical Connections: Dietary Fiber......Page 479
The Role of Polysaccharides in the Structure of Cell Walls......Page 480
16.5 What Are Glycoproteins?......Page 483
Biochemical Connections: Glycoproteins and Blood Transfusions......Page 484
Critical Questions to Review......Page 485
Annotated Bibliography......Page 487
17.1 What Is the Overall Pathway in Glycolysis?......Page 488
A Summary of the Reactions of Glycolysis......Page 489
Biochemical Connections: Louis Pasteur......Page 491
17.2 How Is the 6-Carbon Glucose Converted to the 3-Carbon Glyceraldehyde-3-Phosphate?......Page 492
17.3 How Is Glyceraldehyde-3-Phosphate Converted to Pyruvate?......Page 497
Control Points in the Glycolytic Pathway......Page 503
The Conversion of Pyruvate to Lactate in Muscle......Page 504
Biochemical Connections: Anaerobic Metabolism and Tooth Decay......Page 506
17.5 How Much Energy Can Be Produced by Glycolysis?......Page 508
Summary......Page 509
Critical Questions to Review......Page 510
Annotated Bibliography......Page 511
Breakdown of Glycogen......Page 512
Formation of Glycogen from Glucose......Page 514
Control of Glycogen Metabolism: A Case Study in Control Mechanisms......Page 516
Biochemical Connections: Glycogen Loading......Page 518
Oxaloacetate Is an Intermediate in the Production of Phosphoenolpyruvate in Gluconeogenesis......Page 520
The Role of Sugar Phosphates in Gluconeogenesis......Page 523
Control of Phosphofructokinase and Fructose-1,6-bisphosphatase......Page 524
Control of Hexokinase......Page 528
Nonoxidative Reactions of the Pentose Phosphate Pathway......Page 529
Control of the Pentose Phosphate Pathway......Page 531
Biochemical Connections: The Pentose Phosphate Pathway and Hemolytic Anemia......Page 533
Critical Questions to Review......Page 534
Annotated Bibliography......Page 535
19.1 What Role Does the Citric Acid Cycle Play in Metabolism?......Page 536
19.2 What Is the Overall Pathway of the Citric Acid Cycle?......Page 537
19.3 How Is Pyruvate Converted to Acetyl-CoA?......Page 540
19.4 What Are the Individual Reactions of the Citric Acid Cycle?......Page 543
Biochemical Connections: Plant Poisons and the Citric Acid Cycle......Page 545
19.5 What Are the Energetics of the Citric Acid Cycle, and How Is It Controlled?......Page 550
Control of Pyruvate Dehydrogenase......Page 551
Control of the Citric Acid Cycle Proper......Page 552
19.6 What Is the Glyoxylate Cycle?......Page 553
19.7 What Role Does the Citric Acid Cycle Play in Catabolism?......Page 554
19.8 What Role Does the Citric Acid Cycle Play in Anabolism?......Page 556
Lipid Anabolism......Page 557
Biochemical Connections: Acetyl-CoA......Page 559
Biochemical Connections: Why Is It So Hard to Lose Weight?......Page 561
Critical Questions to Review......Page 562
Annotated Bibliography......Page 564
20.1 What Role Does Electron Transport Play in Metabolism?......Page 565
20.2 What Are the Reduction Potentials for the Electron Transport Chain?......Page 567
20.3 How Are the Electron Transport Complexes Organized?......Page 569
Cytochromes and Other Iron-Containing Proteins of Electron Transport......Page 575
20.4 What Is the Connection between Electron Transport and Phosphorylation?......Page 577
Chemiosmotic Coupling......Page 579
20.6 How Are Respiratory Inhibitors Used to Study Electron Transport?......Page 582
Biochemical Connections: Brown Adipose Tissue: A Case of Useful Inefficiency......Page 583
20.7 What Are Shuttle Mechanisms?......Page 586
20.8 What Is the ATP Yield from Complete Oxidation of Glucose?......Page 587
Biochemical Connections: Sports and Metabolism......Page 588
Critical Questions to Review......Page 590
Annotated Bibliography......Page 592
21.2 How Are Lipids Catabolized?......Page 593
21.3 What Is the Energy Yield from the Oxidation of Fatty Acids?......Page 598
21.4 How Are Unsaturated Fatty Acids and Odd-Carbon Fatty Acids Catabolized?......Page 601
21.5 What Are Ketone Bodies?......Page 602
Biochemical Connections: Ketone Bodies and Effective Weight Loss......Page 604
21.6 How Are Fatty Acids Produced?......Page 605
21.7 How Are Acylglycerols and Compound Lipids Produced?......Page 611
Phosphoacylglycerols......Page 612
Sphingolipids......Page 614
Biochemical Connections: Tay–Sachs Disease......Page 616
21.8 How Is Cholesterol Produced?......Page 617
Cholesterol Is a Precursor of Other Steroids......Page 622
The Role of Cholesterol in Heart Disease......Page 624
Summary......Page 626
Critical Questions to Review......Page 627
Annotated Bibliography......Page 628
22.1 Where Does Photosynthesis Take Place in the Cell?......Page 629
22.2 How Are Photosystems I and II Involved in the Light Reactions of Photosynthesis?......Page 633
Photosystem II:Water Is Split to Produce Oxygen......Page 634
Cyclic Electron Transport in Photosystem I......Page 637
Structure of a Photosystem......Page 638
22.3 How Does Photosynthesis Produce ATP?......Page 640
Biochemical Connections: Some Herbicides Inhibit Photosynthesis......Page 641
22.4 What Are the Evolutionary Implications of Photosynthesis with and without Oxygen?......Page 642
22.5 How Do the Dark Reactions of Photosynthesis Fix CO[sub(2)] into Glucose?......Page 644
Regeneration of Ribulose-1,5-Bisphosphate......Page 646
22.6 How Is CO[sub(2)] Fixed in Tropical Plants?......Page 648
Critical Questions to Review......Page 651
Annotated Bibliography......Page 653
23.1 What Processes Constitute Nitrogen Metabolism?......Page 654
Biochemical Connections: Nitrogen Fertilizers......Page 656
23.3 What Role Does Feedback Inhibition Play in Nitrogen Metabolism?......Page 658
General Features......Page 659
Transamination Reactions: The Role of Glutamate and Pyridoxal Phosphate......Page 660
One-Carbon Transfers and the Serine Family......Page 663
Disposition of the Carbon Skeletons......Page 668
The Urea Cycle......Page 669
Biochemical Connections: Water and the Disposal of Nitrogen Wastes......Page 671
Anabolism of Inosine Monophosphate......Page 673
The Conversion of IMP to AMP and GMP......Page 674
23.8 How Are Purines Catabolized?......Page 676
Biochemical Connections: Lesch–Nyhan Syndrome......Page 678
The Anabolism of Pyrimidine Nucleotides......Page 679
Pyrimidine Catabolism......Page 681
23.10 How Are Ribonucleotides Converted to Deoxyribonucleotides?......Page 682
23.11 How Is dUDP Converted to dTTP?......Page 683
Critical Questions to Review......Page 684
Annotated Bibliography......Page 686
24.1 How Are the Metabolic Pathways Connected?......Page 687
Required Nutrients......Page 688
Biochemical Connections: Alcohol Consumption and Addiction......Page 689
Biochemical Connections: Iron: An Example of a Mineral Requirement......Page 692
Hormones......Page 695
Cyclic AMP and G Proteins......Page 699
Calcium Ion as a Second Messenger......Page 702
Receptor Tyrosine Kinases......Page 704
24.4 How Are Hormones Involved in the Control of Metabolism?......Page 705
Biochemical Connections: Insulin and Low-Carbohydrate Diets......Page 707
Insulin Affects Many Enzymes......Page 709
Diabetes......Page 710
Biochemical Connections: A Workout a Day Keeps Diabetes Away?......Page 711
Critical Questions to Review......Page 712
Annotated Bibliography......Page 714
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Answers to Questions......Page 726
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