Integrative Human Biochemistry: A Textbook for Medical Biochemistry

Leopoldo De Meis’ Legacy: A Biochemistry Textbook with a Difference......Page 6
Foreword to the Second Edition......Page 8
Presentation of Book Structure......Page 10
Preface to the Second Edition......Page 13
References......Page 14
Acknowledgments......Page 15
Contents......Page 16
Part I: The Molecules of Life......Page 25
Chapter 1: Introduction: Life Is Made of Molecules!......Page 26
1.1 Selected Illustrative Example #1: The Molecular Origin of Life......Page 27
1.1.2 The Metabolism Hypothesis......Page 28
1.2 Selected Illustrative Example #2: Viruses—Molecular Machines Interfering with Life......Page 33
1.3 Selected Illustrative Example #3: Molecules as Tools—Drug Discovery and Development......Page 38
Case Description......Page 45
Questions......Page 46
Biochemical Insights......Page 47
Final Discussion......Page 49
Case Description......Page 50
Questions......Page 51
Biochemical Insights......Page 52
Final Discussion......Page 54
Case Description......Page 55
Questions......Page 57
Astrobiology......Page 58
Extraterrestrial Exporting of Life......Page 59
Selected Bibliography......Page 44
Chapter 2: The Chemistry and Physics of Life......Page 60
2.1 The Basics of Chemistry in Cells and Tissues......Page 66
2.1.1 Principal Biological Buffers......Page 73
2.2 More than Only Chemistry: There Is Physics Too......Page 75
Case Description......Page 85
Questions......Page 87
Biochemical Insights......Page 88
Final Discussion......Page 91
Case Description......Page 93
Questions......Page 94
Biochemical Insight......Page 95
Final Discussion: Examples of Missing and Misplaced Colors in Literature and Music......Page 96
Case Description......Page 98
A Modern Interpretation......Page 103
Biochemical Insight......Page 105
Luminescent Art......Page 108
Alternative Case Study: Marie Curie and the Radium Girls......Page 109
Selected Bibliography......Page 84
Chapter 3: The Families of Biological Molecules......Page 111
3.1 Lipids and the Organization of Their Supramolecular Assemblies......Page 112
3.1.1 The Structure of Biological Membranes......Page 120
3.1.2 The Structure of Lipoproteins......Page 127
3.2 Saccharides and Their Polymers and Derivatives......Page 132
3.2.1 From Monomers to Polymers: Polysaccharides......Page 138
3.2.2 Molecular Conjugates of Mono- and Oligosaccharides......Page 139
3.2.3 Molecular Conjugates of Oligosaccharides......Page 145
3.2.4 Polymers of Saccharide Conjugates: Nucleic Acids......Page 148
3.3 Amino Acids and Their Polymers: Peptides and Proteins......Page 153
3.3.1 From Monomers to Polymers: Peptides and Proteins......Page 158
3.3.2 Structure and Function in Proteins......Page 166
3.3.3 Cooperative Interplay Between Tertiary-Level and Quaternary-Level Structure......Page 171
3.3.4 Enzymes......Page 177
3.3.4.1 The Importance of Studying Enzymes......Page 178
3.3.4.2 The Nomenclature of Enzymes......Page 183
Case Description......Page 187
Biochemical Insights......Page 190
Further Reading......Page 191
Case Description......Page 192
3.5.2.1 The Protein Vision......Page 193
The DNA Vertigo......Page 195
Biochemical Insights......Page 196
Final Discussion......Page 197
Case Description......Page 198
Cooking Oil Forms the Matrix of the Fatberg......Page 200
Unraveling the Hidden Dimension of Drug (Ab)Use......Page 201
Fatberg by the Sea......Page 202
Questions......Page 203
Biochemical Insights......Page 204
Final Discussion......Page 206
Selected Bibliography......Page 186
Part II: The Interplay and Regulation of Metabolism......Page 208
Chapter 4: Introduction to Metabolism......Page 209
4.1 Consecutive Reactions Without Enzymes......Page 211
4.2 Consecutive Reactions with Enzymes......Page 217
4.2.1 The Bases of Enzymatic Catalysis and Its Impact in Metabolism......Page 220
Case Description......Page 234
Facts and Figures About Caffeine: Abundant in Nature, Used and Abused by Humans......Page 236
Pharmacokinetics of Caffeine: Absorption, Distribution, and Metabolization......Page 238
Questions......Page 240
Biochemical Insight......Page 241
Final Discussion: Facts and Fantasies About Energy Drinks......Page 248
Description......Page 250
Questions......Page 255
Biochemical Insights......Page 256
Final Discussion......Page 263
Case Description......Page 265
Questions......Page 266
Biochemical Insight......Page 267
Fructose, Obesity, and Insulin Resistance......Page 269
A Suitable Energetic Substrate for a Tireless Cell......Page 270
Selected Bibliography......Page 233
Chapter 5: Regulation of Metabolisms......Page 272
5.1 Levels of Regulation: Impact and Time Scale......Page 277
5.2 Inhibition and Activation of Enzymes by Ligands......Page 279
5.2.1 Nomenclature of Ligands......Page 285
5.3 The Availability of Primary Precursors in a Metabolic Pathway......Page 286
5.3.1 Transport of Metabolites and Effectors Across Membranes......Page 287
5.4 Slower (But Efficient!) Mechanisms of Controlling Enzyme Action......Page 292
5.5 Key Molecules in Energy Metabolism......Page 297
Case Description......Page 302
Questions......Page 306
Biochemical Insights......Page 309
Final Discussion......Page 313
Case Description......Page 315
Biochemical Insights......Page 318
Final Discussion......Page 319
Selected Bibliography......Page 301
Chapter 6: Energy Conservation in Metabolism: The Mechanisms of ATP Synthesis......Page 320
6.1 ATP Synthesis by Substrate-Level Phosphorylation......Page 321
6.1.1 A Historical Perspective of the Fermentation Process Discovery......Page 322
6.1.2 An Overview of the ATP Synthesis by Substrate-Level Phosphorylation During Fermentation......Page 325
6.1.3 Glucose Fermentation Reactions......Page 328
6.2 ATP Synthesis Through Oxidative Phosphorylation......Page 329
6.2.1 A Historical Perspective of the Understanding of Cellular Respiration......Page 331
6.2.2 An Overview of Oxidative Phosphorylation Process......Page 337
6.2.3.1 The Sequence of Electron Transfer Between the Electron Carrier Groups......Page 339
6.2.3.2 The Organization of the Respiratory Complexes in the Inner Mitochondrial Membrane......Page 340
6.2.3.3 The Structure of the Electron-Transferring Components......Page 342
6.2.4 The ATP Synthesis Through Oxidative Phosphorylation......Page 348
6.2.4.1 The Structure of ATP Synthase......Page 349
6.2.4.2 The Mechanism of ATP Synthesis by the ATP Synthase......Page 350
6.2.5 Regulation of Oxidative Phosphorylation......Page 351
6.2.5.1 Uncoupling Proteins: The Physiological Uncouplers......Page 352
6.2.5.2 Production of Reactive Oxygen Species in Mitochondria......Page 355
Case Description......Page 357
Questions......Page 359
Biochemical Insight......Page 360
Final Discussion......Page 361
Case Description......Page 363
Questions......Page 365
Biochemical Insights......Page 368
Final Discussion......Page 372
Case Description......Page 373
Questions......Page 375
Biochemical Insights......Page 376
Final Discussion......Page 379
Selected Bibliography......Page 356
7.1 An Overview of Catabolism......Page 382
7.2 Citric Acid Cycle: The Central Pathway for the Oxidation of the Three Classes of Nutrient Molecules......Page 386
7.2.1 Citric Acid Cycle Reactions......Page 387
7.2.2 Citric Acid Cycle as a Dynamic Pathway......Page 388
7.2.3 A Historical Overview of CAC Discovery......Page 389
7.3 Catabolism of Carbohydrates......Page 392
7.3.1 Carbohydrate Oxidation Reactions......Page 393
7.3.2 Regulation of Pyruvate Conversion to Acetyl-CoA......Page 395
7.4 Catabolism of Lipids......Page 396
7.4.1 TAG Mobilization and Fatty Acid Transport in the Bloodstream......Page 397
7.4.2 Activation of Fatty Acids......Page 398
7.4.3 Fatty Acid Transport into Mitochondria......Page 399
7.4.4 β-Oxidation: The Pathway for Fatty Acid Degradation......Page 400
7.4.4.1 Oxidation of Saturated Fatty Acids with Even Number of Carbons Atoms......Page 402
7.4.4.2 Oxidation of Odd-Chain Fatty Acids......Page 404
7.4.5 Regulation of Fatty Acid Oxidation......Page 405
7.4.6 Fatty Acid Conversion to Ketone Bodies......Page 406
7.5 Catabolism of Amino Acids......Page 407
7.5.1 An Overview of the Amino Acid Catabolism......Page 408
7.5.2.1 Oxidative Deamination of the Amino Acids......Page 409
7.5.2.2 Amino Acid Interconversion: The Transamination Reactions......Page 410
7.5.2.3 Pathways for the Metabolism of the Amino Acid Carbon Skeletons......Page 411
7.5.2.4 Synthesis of Urea for Nitrogen Excretion......Page 413
7.5.3 Amino Acid Metabolism in Other Tissues......Page 415
Case Description......Page 418
Questions......Page 419
7.6.4 Biochemical Insights......Page 420
Final Discussion......Page 421
Case Description......Page 423
Questions......Page 425
Biochemical Insights......Page 426
Final Discussion......Page 430
Selected Bibliography......Page 417
Chapter 8: Metabolic Responses to Hyperglycemia: Regulation and Integration of Metabolism in the Absorptive State......Page 432
8.1 Glucose Sensing by Cells......Page 434
8.2 Biosynthesis of Glycogen......Page 439
8.2.1 Formation of UDP-Glucose......Page 441
8.2.2 Reactions for the Initiation of Glycogen Synthesis from UDP-Glucose......Page 442
8.2.3 Reactions for the Elongation of Glycogen Chain......Page 443
8.2.4 Regulation of Glycogen Synthesis......Page 444
8.3 Biosynthesis of Lipids......Page 450
8.3.1 Synthesis of Fatty Acids......Page 451
8.3.1.1 Reactions for Fatty Acid Synthesis......Page 452
8.3.1.2 Origin of the Acetyl-CoA for the Fatty Acid Synthesis......Page 460
8.3.1.3 Origin of NADPH for the Fatty Acid Synthesis......Page 461
8.3.1.4 Regulation of Fatty Acid Synthesis......Page 465
8.3.2 Synthesis of Triacylglycerols......Page 467
8.4 Hormonal Responses to Hyperglycemia: Role of Insulin......Page 468
8.4.1 Discovery of Insulin......Page 469
8.4.2 Mechanisms of Insulin Action......Page 470
8.4.3.1 Effects of Insulin on Glucose Uptake by Muscle and Adipose Tissue......Page 474
8.4.3.2 Effects of Insulin on Metabolic Pathways......Page 475
8.5 Metabolic Interplay in Response to Hyperglycemia......Page 476
Case Description......Page 478
Questions......Page 480
Biochemical Insights......Page 481
Final Discussion......Page 484
HCV Infection......Page 485
Case Description......Page 486
Questions......Page 487
Biochemical Insights......Page 488
Insulin as Weapon......Page 492
Insulin Sources Over Time......Page 493
Beyond Hyperinsulinemia-Induced Hypoglycemia......Page 494
Selected Bibliography......Page 477
Chapter 9: Regulation and Integration of Metabolism During Hypoglycemia......Page 495
9.1 Overview of Metabolism During Fasting: Exemplifying with Studies on Therapeutic Starvation......Page 498
9.2 Glycogen Degradation in the Liver......Page 502
9.2.1 Reactions of Glycogen Degradation......Page 504
9.2.2 Regulation of Glycogen Degradation in the Liver......Page 507
9.3.1 Gluconeogenesis Reactions......Page 509
9.3.2 Precursors for the Synthesis of Glucose......Page 513
9.3.3 Regulation of Gluconeogenesis......Page 514
9.3.4 Dynamic Utilization of Gluconeogenesis Precursors......Page 516
9.4 Hormonal Responses to Hypoglycemia......Page 519
9.4.1 Glucagon: Mechanism of Action and Effects on Energy Metabolism......Page 520
9.4.1.1 Effects of Glucagon on Liver Metabolism......Page 523
9.4.1.2 Effects of Glucagon on the Adipose Tissue......Page 524
9.4.2 Glucocorticoids: Mechanism of Action and Effects on Energy Metabolism......Page 525
9.4.2.1 Effects of Glucocorticoids on Muscle Metabolism......Page 527
9.4.2.2 Effects of Glucocorticoids on Liver Metabolism......Page 528
Case Description......Page 530
Questions......Page 531
Biochemical Insight......Page 532
Final Discussion......Page 534
Description......Page 535
Questions......Page 536
Biochemical Insights......Page 537
Lychee Breeding and Lychee Overeating......Page 539
Case Description......Page 540
Questions......Page 541
Biochemical Insight......Page 542
Final Discussion......Page 543
Selected Bibliography......Page 529
Chapter 10: Regulation and Integration of Metabolism During Physical Activity......Page 545
10.1.1 Structural Organization of the Contractile Apparatus......Page 546
10.1.1.1 The Main Proteic Components of the Contractile Apparatus......Page 549
10.1.2.1 The Sliding Filaments Model......Page 552
10.1.3 Regulation of Muscle Contraction......Page 554
10.2 Different Metabolic Profiles of the Skeletal Muscle Fibers......Page 556
10.3 Overview of ATP Synthesis in the Muscle Cells......Page 558
10.4.1 Role of the Cellular Energy Charge in the Muscle Cell Metabolism......Page 560
10.4.1.1 The AMP-Activated Protein Kinase: A Cellular Energy Sensor......Page 562
10.4.2.1 Fatty Acid Oxidation in Skeletal Muscle......Page 564
10.4.2.2 Insulin-Independent Glucose Uptake in Skeletal Muscle......Page 567
10.4.2.3 Glycogen Degradation in Skeletal Muscle......Page 568
10.4.2.4 Glycolysis in Skeletal Muscle......Page 570
10.5 Hormonal Regulation During Physical Activity: Role of Adrenaline......Page 571
10.5.1 Molecular Mechanisms of Adrenaline Action......Page 572
10.5.1.1 Cellular Receptors for Adrenaline......Page 573
10.5.2.1 Effects of Adrenaline on the Adipose Tissue Metabolism......Page 574
10.5.2.3 Effects of Adrenaline on Muscle Metabolism......Page 575
Case Description......Page 578
Questions......Page 582
Biochemical Insights......Page 583
Final Discussion......Page 587
Case Description......Page 589
Questions......Page 591
Biochemical Insights......Page 592
Final Discussion......Page 598
Case Description......Page 600
Questions......Page 602
Biochemical Insights......Page 604
Final Discussion......Page 606
Selected Bibliography......Page 577
Chapter 11: Control of Body Weight and the Modern Metabolic Diseases......Page 608
11.1 Humoral Control of Food Ingestion......Page 610
11.1.1 A Historical Perspective of the Role of Hypothalamus in Food Intake......Page 611
11.1.2 Leptin: A Hormone Indicative of Adiposity......Page 613
11.1.3 Intestinal Peptides: Triggers of Postprandial Satiety......Page 617
11.1.4 Ghrelin: The Main Orexigenic Hormone......Page 621
11.1.5 The Arcuate Nucleus and the Melanocortin System......Page 623
11.2.1 Adaptive Thermogenesis......Page 625
11.2.1.1 Cold-Induced Thermogenesis......Page 626
11.2.1.2 Diet-Induced Thermogenesis......Page 628
11.2.2 Role of Thyroid Hormones......Page 629
11.3 Obesity and the Metabolic Syndrome......Page 634
11.3.1 Chronic Inflammation and Insulin Resistance in Obesity......Page 635
11.3.2 Origin of Inflammation in Obesity......Page 637
Case Description......Page 641
Questions......Page 644
Biochemical Insights......Page 645
Anti-obesity Medications: Pharmacological Strategies for Obesity Control......Page 648
Case Description......Page 651
Questions......Page 653
Biochemical Insights......Page 654
Final Discussion......Page 657
Case Description......Page 658
Questions......Page 659
Biochemical Insights......Page 660
Final Discussion......Page 661
Selected Bibliography......Page 640
Credits......Page 662
Index......Page 663