Glutathione and Sulfur Amino Acids in Human Health and Disease

GLUTATHIONE AND SULFUR AMINO ACIDS IN HUMAN HEALTH AND DISEASE......Page 3
CONTENTS......Page 7
PREFACE......Page 17
CONTRIBUTORS......Page 21
I INTRODUCTION......Page 25
1.1 Introduction......Page 27
1.2 Why Sulfur-Containing Amino Acids?......Page 28
1.3 S-Adenosylmethionine, Nature’s Wonder Cofactor......Page 31
1.4 Glutathione......Page 34
1.5 Taurine—the Second Essential Sulfur-Containing Amino Acid?......Page 37
References......Page 39
II CHEMISTRY AND METABOLISM OF GSH AND SULFUR AMINO ACIDS......Page 43
2.2 Sulfur Amino Acids (SAA) Content of Dietary Protein......Page 45
2.4 Nutritional Requirement for Total Sulfur Amino Acids......Page 48
2.5 Conclusions......Page 53
References......Page 54
3.1 Introduction......Page 59
3.2 Glutathione Content in Cells......Page 60
References......Page 66
4.1 Introduction......Page 71
4.2 Isotopic Approaches to Study Metabolism......Page 73
4.3 Evidence of Gut Sulfur Amino Acid Metabolism......Page 74
4.4 Other Key Players in Intestinal Sulfur Amino Acid Metabolism......Page 77
4.5 Cysteine in Redox Function and Oxidant Stress in the Gut......Page 82
4.6 Pathophysiology of Sulfur Amino Acid Metabolism in the GIT......Page 83
4.7 Conclusions......Page 88
References......Page 89
5.2 Dietary Relation between Methionine and Cysteine......Page 97
5.3 Metabolic Relation between Hepatic Sulfur Amino Acids, B Vitamins, and Methyl Group Metabolism......Page 99
5.4 Regulation of Sulfur Amino Acid Metabolism and Related Metabolic Pathways in the Liver......Page 101
5.5 Impact of Physiologic and Nutritional Factors on Sulfur Amino Acid Metabolism......Page 105
References......Page 108
III ANTIOXIDANT AND DETOXIFICATION ACTIVITIES......Page 115
6.1 Introduction......Page 117
6.2 Reactive Oxygen Species and Antioxidants......Page 118
6.3 Glutathione Redox Cycle......Page 122
6.4 Regulation of GSH and Cysteine Levels......Page 126
6.5 Biotransformation......Page 130
6.6 ROS-Mediated Cellular Signaling......Page 133
6.7 Transcription Regulation of Antioxidant and Conjugation Enzymes......Page 134
6.8 Oxidative Stress and Diseases......Page 135
References......Page 137
7.1 Introduction......Page 145
7.2 General Characteristics of Glutaredoxins......Page 148
7.3 General Characteristics of Thioredoxins......Page 150
7.4 Glutaredoxin Mechanism of Action......Page 152
7.5 Thioredoxin Mechanism of Action......Page 156
7.6 Control of Grx Expression......Page 157
7.7 Control of Trx Expression in Mammalian Systems......Page 158
7.8 Cellular Functions of Grx......Page 159
7.9 Cellular Functions of Trx......Page 163
7.10 Reversible Sulfhydryl Oxidation and Disease......Page 166
7.11 Conclusions......Page 169
References......Page 170
8.1 Introduction......Page 181
8.2 History of the Msr System......Page 182
8.3 MsrA and MsrB Protein Structure and Mechanism of Action......Page 184
8.4 Msr Reducing Requirement......Page 186
8.5 Other Members of the Msr Family......Page 189
8.6 The Msr System: Both a Repair Enzyme and a Scavenger of ROS......Page 190
8.7 Genetic Studies on the Role of the Msr System in Protecting Cells Against Oxidative Damage......Page 191
8.8 Evidence that Oxidative Damage is a Major Factor in Aging: Role of Mitochondria and the Msr System......Page 194
8.9 How can the Msr System be Utilized for Drug Development?......Page 198
8.10 Methionine Sulfoxide and Disease......Page 200
Acknowledgment......Page 204
References......Page 205
IV BIOACTIVITY OF GSH AND SULFUR AMINO ACIDS AS REGULATORS OF CELLULAR PROCESSES......Page 213
9.1 Introduction......Page 215
9.2 Glutathione and Redox Regulation in Immunity......Page 216
9.3 Protein Cysteine Oxidation......Page 217
9.4 Mechanisms for PSSG Formation and the Complex Scenario of Protein Glutathionylation......Page 220
9.5 Deglutathionylation......Page 223
9.6 Identification of Proteins Undergoing Glutathionylation......Page 224
9.7 Functional Consequences of Protein Glutathionylation......Page 226
References......Page 227
10.1 Introduction......Page 235
10.2 Synthesis and Functions of GSH......Page 237
10.3 Apoptosis: A Programmed Mode to Die......Page 245
10.4 Role of GSH and Cysteine in Apoptosis......Page 248
10.5 Sulfur Amino Acids in Apoptosis......Page 263
10.6 Concluding Remarks and Recent Progress......Page 265
References......Page 266
11.1 Introduction......Page 281
11.2 The Methionine Sulfoxide Reductase System......Page 282
11.3 Methionine Sulfoxide Reductase and Selenium......Page 283
11.4 Methionine Sulfoxide Reductase: A Knockout Mouse as a Model for Neurodegenerative Diseases......Page 286
11.5 Regulation of Protein Expression/Function by the Methionine Sulfoxide Reductase System......Page 288
11.6 Conclusions......Page 290
References......Page 291
12.1 The Biochemistry of Sulfur Amino Acids......Page 297
12.2 Sulfur Amino Acid and Glutathione Metabolism Following Infection and Injury......Page 299
12.3 Glutathione and the Immune System......Page 302
12.4 Mechanism of the Effect of Oxidants and Antioxidants on Inflammation and Immune Function......Page 304
12.5 Strategies for Modulating Tissue Glutathione Content and Influencing Immune Function......Page 306
12.7 Conclusions......Page 308
References......Page 309
V GSH AND SULFUR AMINO ACIDS IN PATHOLOGICAL PROCESSES......Page 313
13.2 Sulfur Amino Acid Deficiency......Page 315
13.3 Sulfur Amino Acid Toxicity......Page 323
References......Page 329
14.2 Biosynthesis and Metabolism of Methionine and Cysteine......Page 341
14.3 Defects in the Transulfuration Pathway......Page 343
14.4 Inherited Defects in Membrane Transport......Page 345
14.5 Pathologies Associated with Folic Acid Metabolizing Enzymes......Page 347
14.6 Heterogeneity of GSH Metabolizing Enzymes and Associated Human Pathologies......Page 350
References......Page 357
15.1 Introduction......Page 367
15.3 The γ-Glutamyl Cycle......Page 369
15.4 Inborn Errors in the Metabolism of GSH......Page 370
Acknowledgments......Page 379
References......Page 380
16.1 Introduction......Page 387
16.2 An Overview of Hcy Metabolism......Page 389
16.3 Toxicity of Hcy and Its Metabolites......Page 390
16.4 Physical-Chemical Properties of Hcy-Thiolactone......Page 393
16.5 The Mechanism of Hcy-Thiolactone Biosynthesis......Page 398
16.6 Structural and Functional Consequences of Protein Modification by Hcy-Thiolactone......Page 402
16.7 The Hcy-Thiolactone Hypothesis of Vascular Disease......Page 406
16.8 Pathophysiologic Consequences of Protein N-Homocysteinylation......Page 411
16.9 Urinary Elimination of Hcy-Thiolactone......Page 417
16.10 Enzymatic Elimination of Hcy-Thiolactone......Page 419
References......Page 421
17.1 Introduction......Page 437
17.2 Homocysteine Metabolism......Page 438
17.4 Homocysteine Measurement......Page 439
17.5 Causes of Hyperhomocysteinemia......Page 441
17.7 Epidemiologic Evidence Linking Homocysteine and Atherothrombotic Vascular Disease......Page 442
17.8 Homocysteine and Atherothrombosis: Pathophysiologic Mechanisms......Page 446
17.9 Impact of Homocysteine-Lowering Therapy on Atherothrombotic Vascular Disease......Page 448
17.10 Conclusions......Page 455
References......Page 456
18.1 Introduction......Page 465
18.2 What is an “Abnormal” Plasma Homocysteine Level in Clinical Studies of Neurological Disease?......Page 467
18.4 Hyperhomocysteinemia and the Risk of Stroke......Page 468
18.5 Elevated Plasma Homocysteine Levels are Associated with the Risk of Dementia and Alzheimer’s Disease......Page 471
18.6 Parkinson’s Disease......Page 479
References......Page 480
19.1 Introduction......Page 495
19.2 Carcinogenesis, Tumor Growth, and Cell Death......Page 496
19.3 Intercellular and Interorgan Transport of GSH in Tumor-Bearing Mammals......Page 503
19.4 GSH and the Interaction of Metastatic Cells with the Vascular Endothelium......Page 504
19.5 Adaptive Response in Invasive Cells......Page 507
19.6 GSH Depletion and the Sensitization of Cancer Cells to Therapy......Page 508
References......Page 511
VI GSH AND SULFUR AMINO ACIDS AS DRUGS AND NUTRACEUTICALS......Page 525
20.1 Introduction......Page 527
20.2 Intracellular GSH Status during Viral Infection......Page 528
20.4 Role of Constitutive GSH Levels in Controlling Cell Susceptibility to Viral Infection......Page 530
20.5 Effect of Intracellular GSH Depletion on Viral Replication......Page 532
20.6 Effect of Exogenous GSH and GSH Derivatives on Viral Replication......Page 535
20.7 In Vivo Effects of Systemic and Topic GSH Administration......Page 537
References......Page 539
21.1 Introduction......Page 543
21.2 Oxidative Stress in COPD......Page 544
21.3 Pharmacology of N-Acetylcysteine......Page 546
21.4 Pulmonary Antioxidant and Anti-Inflammatory Effects......Page 548
21.5 Nonpulmonary Effects......Page 550
21.6 Clinical Efficacy of N-Acetylcysteine in COPD......Page 552
21.7 Idiopathic Pulmonary Fibrosis......Page 555
21.8 Other Disorders......Page 556
21.9 Conclusions......Page 557
References......Page 558
22.1 Introduction......Page 567
22.2 The Unique Character of Taurine: Basis for Distinguished Behavior......Page 568
22.3 Functional Properties of Taurine......Page 570
22.5 Taurine Concentration in Fetal Development and Neonatal Growth......Page 573
22.6 Beneficial Actions of Taurine......Page 575
22.7 Taurine and Diabetes......Page 578
22.8 Taurine and the Cardiovascular System......Page 579
22.9 Taurine and Endothelial Dysfunction......Page 581
22.10 Taurine and Lung Dysfunction......Page 582
22.12 Retinal Protection......Page 583
22.13 Anticancer Activity of Taurine......Page 584
22.14 Taurine in Bone Tissue Formation and Inhibition of Bone Loss......Page 585
22.15 Taurine and Smoking......Page 586
22.16 Taurine as an Antialcohol Molecule......Page 587
22.17 Taurine as Functional Food and Supplement......Page 588
22.18 Conclusions......Page 589
References......Page 590
SUBJECT INDEX......Page 605