Principles of Biochemistry, 5th Edition

Cover......Page 1
Title Page......Page 5
Copyright Page......Page 6
Acknowledgments......Page 33
Contents......Page 10
To the Student......Page 25
Preface......Page 27
About the Authors......Page 35
1 Introduction to Biochemistry......Page 37
1.1 Biochemistry Is a Modern Science......Page 38
1.2 The Chemical Elements of Life......Page 39
1.3 Many Important Macromolecules Are Polymers......Page 40
1.4 The Energetics of Life......Page 46
1.5 Biochemistry and Evolution......Page 51
1.7 Prokaryotic Cells: Structural Features......Page 53
1.8 Eukaryotic Cells: Structural Features......Page 54
1.9 A Picture of the Living Cell......Page 59
Appendix: The Special Terminology of Biochemistry......Page 62
Selected Readings......Page 63
2 Water......Page 64
2.1 The Water Molecule Is Polar......Page 65
2.2 Hydrogen Bonding in Water......Page 66
2.3 Water Is an Excellent Solvent......Page 68
2.4 Nonpolar Substances Are Insoluble in Water......Page 71
2.5 Noncovalent Interactions......Page 73
2.6 Water Is Nucleophilic......Page 75
2.7 Ionization of Water......Page 77
2.8 The pH Scale......Page 79
2.9 Acid Dissociation Constants of Weak Acids......Page 80
2.10 Buffered Solutions Resist Changes in pH......Page 86
Problems......Page 88
Selected Readings......Page 90
3 Amino Acids and the Primary Structures of Proteins......Page 91
3.1 General Structure of Amino Acids......Page 92
3.2 Structures of the 20 Common Amino Acids......Page 94
3.3 Other Amino Acids and Amino Acid Derivatives......Page 98
3.4 Ionization of Amino Acids......Page 99
3.5 Peptide Bonds Link Amino Acids in Proteins......Page 103
3.6 Protein Purification Techniques......Page 104
3.7 Analytical Techniques......Page 106
3.8 Amino Acid Composition of Proteins......Page 109
3.9 Determining the Sequence of Amino Acid Residues......Page 110
3.10 Protein Sequencing Strategies......Page 112
3.11 Comparisons of the Primary Structures of Proteins Reveal Evolutionary Relationships......Page 115
Problems......Page 118
Selected Readings......Page 120
4 Proteins: Three-Dimensional Structure and Function......Page 121
4.1 There Are Four Levels of Protein Structure......Page 123
4.2 Methods for Determining Protein Structure......Page 124
4.3 The Conformation of the Peptide Group......Page 127
4.4 The α
Helix......Page 130
4.5 β Strands and β
 Sheets......Page 133
4.6 Loops and Turns......Page 134
4.7 Tertiary Structure of Proteins......Page 135
4.8 Quaternary Structure......Page 139
4.9 Protein–Protein Interactions......Page 145
4.10 Protein Denaturation and Renaturation......Page 146
4.11 Protein Folding and Stability......Page 150
4.12 Collagen, a Fibrous Protein......Page 155
4.13 Structure of Myoglobin and Hemoglobin......Page 158
4.14 Oxygen Binding to Myoglobin and Hemoglobin......Page 159
4.15 Antibodies Bind Specific Antigens......Page 165
Summary......Page 166
Problems......Page 167
Selected Readings......Page 169
5 Properties of Enzymes......Page 170
5.1 The Six Classes of Enzymes......Page 172
5.2 Kinetic Experiments Reveal Enzyme Properties......Page 174
5.3 The Michaelis-Menten Equation......Page 176
5.4 Kinetic Constants Indicate Enzyme Activity and Catalytic Proficiency......Page 180
5.5 Measurement of K[sub(m)] and V[sub(max)]......Page 181
5.6 Kinetics of Multisubstrate Reactions......Page 183
5.7 Reversible Enzyme Inhibition......Page 184
5.8 Irreversible Enzyme Inhibition......Page 188
5.9 Regulation of Enzyme Activity......Page 189
5.10 Multienzyme Complexes and Multifunctional Enzymes......Page 194
Problems......Page 195
Selected Readings......Page 197
6.1 The Terminology of Mechanistic Chemistry......Page 198
6.2 Catalysts Stabilize Transition States......Page 200
6.3 Chemical Modes of Enzymatic Catalysis......Page 202
6.4 Diffusion-Controlled Reactions......Page 207
6.5 Modes of Enzymatic Catalysis......Page 211
6.6 Serine Proteases......Page 219
6.7 Lysozyme......Page 223
6.8 Arginine Kinase......Page 226
Summary......Page 228
Problems......Page 229
Selected Readings......Page 230
7 Coenzymes and Vitamins......Page 232
7.2 Coenzyme Classification......Page 233
7.3 ATP and Other Nucleotide Cosubstrates......Page 234
7.4 NAD+ and NADP+
......Page 236
7.6 Coenzyme A and Acyl Carrier Protein......Page 240
7.7 Thiamine Diphosphate......Page 242
7.8 Pyridoxal Phosphate......Page 243
7.9 Vitamin C......Page 245
7.10 Biotin......Page 247
7.11 Tetrahydrofolate......Page 249
7.12 Cobalamin......Page 251
7.13 Lipoamide......Page 252
7.14 Lipid Vitamins......Page 253
7.15 Ubiquinone......Page 255
7.17 Cytochromes......Page 257
Summary......Page 259
Problems......Page 260
Selected Readings......Page 262
8 Carbohydrates......Page 263
8.1 Most Monosaccharides Are Chiral Compounds......Page 264
8.2 Cyclization of Aldoses and Ketoses......Page 266
8.3 Conformations of Monosaccharides......Page 270
8.4 Derivatives of Monosaccharides......Page 271
8.5 Disaccharides and Other Glycosides......Page 272
8.6 Polysaccharides......Page 276
8.7 Glycoconjugates......Page 280
Summary......Page 288
Problems......Page 289
Selected Readings......Page 290
9.1 Structural and Functional Diversity of Lipids......Page 292
9.2 Fatty Acids......Page 293
9.3 Triacylglycerols......Page 297
9.4 Glycerophospholipids......Page 298
9.5 Sphingolipids......Page 299
9.6 Steroids......Page 302
9.7 Other Biologically Important Lipids......Page 304
9.8 Biological Membranes......Page 305
9.9 Membranes Are Dynamic Structures......Page 311
9.10 Membrane Transport......Page 313
9.11 Transduction of Extracellular Signals......Page 319
Summary......Page 327
Problems......Page 328
Selected Readings......Page 329
10.1 Metabolism Is a Network of Reactions......Page 330
10.2 Metabolic Pathways......Page 333
10.3 Major Pathways in Cells......Page 338
10.4 Compartmentation and Interorgan Metabolism......Page 340
10.5 Actual Gibbs Free Energy Change, Not Standard Free Energy Change, Determines the Direction of Metabolic Reactions......Page 342
10.6 The Free Energy of ATP Hydrolysis......Page 344
10.7 The Metabolic Roles of ATP......Page 347
10.9 Reduced Coenzymes Conserve Energy from Biological Oxidations......Page 352
10.10 Experimental Methods for Studying Metabolism......Page 357
Summary......Page 358
Problems......Page 359
Selected Readings......Page 360
11 Glycolysis......Page 361
11.2 The Ten Steps of Glycolysis......Page 362
11.3 The Fate of Pryuvate......Page 374
11.4 Free Energy Changes in Glycolysis......Page 377
11.5 Regulation of Glycolysis......Page 379
11.6 Other Sugars Can Enter Glycolysis......Page 383
11.7 The Entner–Doudoroff Pathway in Bacteria......Page 387
Summary......Page 388
Problems......Page 389
Selected Readings......Page 390
12 Gluconeogenesis, the Pentose Phosphate Pathway, and Glycogen Metabolism......Page 391
12.1 Gluconeogenesis......Page 392
12.2 Precursors for Gluconeogenesis......Page 396
12.3 Regulation of Gluconeogenesis......Page 399
12.4 The Pentose Phosphate Pathway......Page 400
12.5 Glycogen Metabolism......Page 404
12.6 Regulation of Glycogen Metabolism in Mammals......Page 408
12.7 Maintenance of Glucose Levels in Mammals......Page 414
12.8 Glycogen Storage Diseases......Page 417
Problems......Page 418
Selected Readings......Page 419
13 The Citric Acid Cycle......Page 421
13.1 Conversion of Pyruvate to Acetyl CoA......Page 423
13.2 The Citric Acid Cycle Oxidizes Acetyl CoA......Page 427
13.3 The Citric Acid Cycle Enzymes......Page 430
13.4 Entry of Pyruvate Into Mitochondria......Page 438
13.5 Reduced Coenzymes Can Fuel the Production of ATP......Page 441
13.6 Regulation of the Citric Acid Cycle......Page 442
13.7 The Citric Acid Cycle Isn’t Always a “Cycle”......Page 443
13.8 The Glyoxylate Pathway......Page 445
13.9 Evolution of the Citric Acid Cycle......Page 448
Problems......Page 450
Selected Readings......Page 452
14 Electron Transport and ATP Synthesis......Page 453
14.2 The Mitochondrion......Page 454
14.3 The Chemiosmotic Theory and the Protonmotive Force......Page 456
14.4 Electron Transport......Page 459
14.5 Complex I......Page 462
14.6 Complex II......Page 463
14.7 Complex III......Page 464
14.8 Complex IV......Page 467
14.9 Complex V: ATP Synthase......Page 469
14.10 Active Transport of ATP, ADP, and Pi Across the Mitochondrial Membrane......Page 471
14.12 NADH Shuttle Mechanisms in Eukaryotes......Page 472
14.13 Other Terminal Electron Acceptors and Donors......Page 475
14.14 Superoxide Anions......Page 476
Problems......Page 477
Selected Readings......Page 478
15 Photosynthesis......Page 479
15.1 Light-Gathering Pigments......Page 480
15.2 Bacterial Photosystems......Page 484
15.3 Plant Photosynthesis......Page 494
15.4 Fixation of CO[sub(2)]: The Calvin Cycle......Page 497
15.5 Sucrose and Starch Metabolism in Plants......Page 503
15.6 Additional Carbon Fixation Pathways......Page 505
Summary......Page 508
Problems......Page 509
Selected Readings......Page 510
16.1 Fatty Acid Synthesis......Page 511
16.2 Synthesis of Triacylglycerols and Glycerophospholipids......Page 517
16.3 Synthesis of Eicosanoids......Page 519
16.4 Synthesis of Ether Lipids......Page 523
16.6 Synthesis of Cholesterol......Page 524
16.7 Fatty Acid Oxidation......Page 529
16.8 Eukaryotic Lipids Are Made at a Variety of Sites......Page 536
16.9 Lipid Metabolism Is Regulated by Hormones in Mammals......Page 537
16.10 Absorption and Mobilization of Fuel Lipids in Mammals......Page 541
16.11 Ketone Bodies Are Fuel Molecules......Page 544
Problems......Page 547
Selected Readings......Page 549
17 Amino Acid Metabolism......Page 550
17.1 The Nitrogen Cycle and Nitrogen Fixation......Page 551
17.2 Assimilation of Ammonia......Page 554
17.3 Synthesis of Amino Acids......Page 556
17.4 Amino Acids as Metabolic Precursors......Page 565
17.5 Protein Turnover......Page 567
17.6 Amino Acid Catabolism......Page 570
17.7 The Urea Cycle Converts Ammonia into Urea......Page 578
17.8 Renal Glutamine Metabolism Produces Bicarbonate......Page 583
Problems......Page 584
Selected Readings......Page 585
18.1 Synthesis of Purine Nucleotides......Page 586
18.2 Other Purine Nucleotides Are Synthesized from IMP......Page 590
18.3 Synthesis of Pyrimidine Nucleotides......Page 591
18.4 CTP Is Synthesized from UMP......Page 595
18.6 Methylation of dUMP Produces dTMP......Page 596
18.8 Salvage of Purines and Pyrimidines......Page 600
18.9 Purine Catabolism......Page 601
18.10 Pyrimidine Catabolism......Page 604
Problems......Page 607
Selected Readings......Page 608
19 Nucleic Acids......Page 609
19.1 Nucleotides Are the Building Blocks of Nucleic Acids......Page 610
19.2 DNA Is Double-Stranded......Page 615
19.3 DNA Can Be Supercoiled......Page 622
19.4 Cells Contain Several Kinds of RNA......Page 623
19.5 Nucleosomes and Chromatin......Page 624
19.6 Nucleases and Hydrolysis of Nucleic Acids......Page 627
19.7 Uses of Restriction Endocucleases......Page 632
Summary......Page 634
Selected Readings......Page 635
20 DNA Replication, Repair, and Recombination......Page 637
20.1 Chromosomal DNA Replication Is Bidirectional......Page 638
20.2 DNA Polymerase......Page 639
20.3 DNA Polymerase Synthesizes Two Strands Simultaneously......Page 643
20.4 Model of the Replisome......Page 646
20.6 DNA Replication in Eukaryotes......Page 651
20.7 DNA Replication in Eukaryotes......Page 655
20.8 Repair of Damaged DNA......Page 659
20.9 Homologous Recombination......Page 662
Problems......Page 667
Selected Readings......Page 668
21 Transcription and RNA Processing......Page 669
21.1 Types of RNA......Page 670
21.2 RNA Polymerase......Page 671
21.3 Transcription Initiation......Page 674
21.4 Transcription Termination......Page 679
21.5 Transcription in Eukaryotes......Page 681
21.6 Transcription of Genes Is Regulated......Page 684
21.7 The lac Operon, an Example of Negative and Positive Regulation......Page 686
21.8 Post-transcriptional Modification of RNA......Page 690
21.9 Eukaryotic mRNA Processing......Page 691
Summary......Page 698
Problems......Page 699
Selected Readings......Page 700
22.1 The Genetic Code......Page 701
22.2 Transfer RNA......Page 704
22.3 Aminoacyl-tRNA Synthetases......Page 706
22.4 Ribosomes......Page 709
22.5 Initiation of Translation......Page 711
22.6 Chain Elongation During Protein Synthesis Is a Three-Step Microcycle......Page 715
22.8 Protein Synthesis Is Energetically Expensive......Page 720
22.9 Regulation of Protein Synthesis......Page 721
22.10 Post-translational Processing......Page 725
Summary......Page 730
Problems......Page 731
Selected Readings......Page 732
Solutions......Page 733
A......Page 787
C......Page 788
E......Page 790
G......Page 791
H......Page 792
K......Page 793
M......Page 794
N......Page 795
P......Page 796
R......Page 798
S......Page 799
T......Page 800
V......Page 801
Z......Page 802
Illustration Credits......Page 803
A......Page 805
B......Page 806
C......Page 807
D......Page 809
E......Page 810
G......Page 811
I......Page 813
L......Page 814
M......Page 815
O......Page 816
P......Page 817
R......Page 819
S......Page 820
T......Page 821
Z......Page 822