Glutathione and Sulfur Amino Acids in Human Health and Disease

The complex roles of glutathione and sulfur amino acids in human health Glutathione (γ-L-glutamyl-L-cysteinylglycine, GSH) is a major antioxidant acting as a free radical scavenger that protects the cell from reactive oxygen species (ROS). Sulfur amino acids (SAAs), such as methionine and cysteine, play a critical role in the maintenance of health. GSH depletion as well as alterations of SAA metabolism are linked to a host of disease states including liver cirrhosis, various pulmonary diseases, myocardial ischemia and reperfusion injury, aging, Parkinson's disease, Alzheimer's disease, sepsis, and others. This book provides researchers with a comprehensive review of the biochemistry, absorption, metabolism, biological activities, disease prevention, and health promotion of glutathione and sulfur amino acids. The twenty-two chapters explore such topics as: Chemistry, absorption, transport, and metabolism of GSH and sulfur amino acids Antioxidant and detoxification properties of GSH and sulfur amino acids, highlighting the enzymatic systems involved in antioxidant defenses Biological activities of GSH and sulfur amino acids and their role in modulating cell processes Role of GSH and sulfur amino acid deficiency and alteration in the onset of diseases and in aging Protective effects exerted by GSH and sulfur amino acids when used as drugs, functional foods, and nutraceuticals in humans and animals Special attention is paid to the molecular mechanisms for the modulation of transcription factors and enzyme activities, as well as the nutritional and therapeutic significance of dietary sulfur amino acids as shown in human and animal models. With more than 2,000 scientific references, this book provides food scientists, nutritionists, biochemists, food technologists, chemists, molecular biologists, and public health professionals with a comprehensive and up-to-date examination of 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