GLUTATHIONE AND SULFUR AMINO ACIDS IN HUMAN HEALTH AND DISEASE -- CONTENTS -- PREFACE -- CONTRIBUTORS -- I INTRODUCTION -- 1 GLUTATHIONE AND THE SULFUR-CONTAINING AMINO ACIDS: AN OVERVIEW -- 1.1 Introduction -- 1.2 Why Sulfur-Containing Amino Acids? -- 1.3 S-Adenosylmethionine, Nature's Wonder Cofactor -- 1.4 Glutathione -- 1.5 Taurine-the Second Essential Sulfur-Containing Amino Acid? -- 1.6 Conclusions -- Acknowledgments -- References -- II CHEMISTRY AND METABOLISM OF GSH AND SULFUR AMINO ACIDS -- 2 SULFUR AMINO ACIDS CONTENTS OF DIETARY PROTEINS: DAILY INTAKE AND REQUIREMENTS -- 2.1 Introduction -- 2.2 Sulfur Amino Acids (SAA) Content of Dietary Protein -- 2.3 Sulfur Amino Acid Intake -- 2.4 Nutritional Requirement for Total Sulfur Amino Acids -- 2.5 Conclusions -- References -- 3 CELLULAR COMPARTMENTALIZATION OF GLUTATHIONE -- 3.1 Introduction -- 3.2 Glutathione Content in Cells -- References -- 4 INTESTINAL METABOLISM OF SULFUR AMINO ACIDS -- 4.1 Introduction -- 4.2 Isotopic Approaches to Study Metabolism -- 4.3 Evidence of Gut Sulfur Amino Acid Metabolism -- 4.4 Other Key Players in Intestinal Sulfur Amino Acid Metabolism -- 4.5 Cysteine in Redox Function and Oxidant Stress in the Gut -- 4.6 Pathophysiology of Sulfur Amino Acid Metabolism in the GIT -- 4.7 Conclusions -- References -- 5 HEPATIC SULFUR AMINO ACID METABOLISM -- 5.1 Introduction -- 5.2 Dietary Relation between Methionine and Cysteine -- 5.3 Metabolic Relation between Hepatic Sulfur Amino Acids, B Vitamins, and Methyl Group Metabolism -- 5.4 Regulation of Sulfur Amino Acid Metabolism and Related Metabolic Pathways in the Liver -- 5.5 Impact of Physiologic and Nutritional Factors on Sulfur Amino Acid Metabolism -- 5.6 Conclusions -- References -- III ANTIOXIDANT AND DETOXIFICATION ACTIVITIES.

6 GLUTATHIONE AND SULFUR CONTAINING AMINO ACIDS: ANTIOXIDANT AND CONJUGATION ACTIVITIES -- 6.1 Introduction -- 6.2 Reactive Oxygen Species and Antioxidants -- 6.3 Glutathione Redox Cycle -- 6.4 Regulation of GSH and Cysteine Levels -- 6.5 Biotransformation -- 6.6 ROS-Mediated Cellular Signaling -- 6.7 Transcription Regulation of Antioxidant and Conjugation Enzymes -- 6.8 Oxidative Stress and Diseases -- References -- 7 GLUTAREDOXIN AND THIOREDOXIN ENZYME SYSTEMS: CATALYTIC MECHANISMS AND PHYSIOLOGICAL FUNCTIONS -- 7.1 Introduction -- 7.2 General Characteristics of Glutaredoxins -- 7.3 General Characteristics of Thioredoxins -- 7.4 Glutaredoxin Mechanism of Action -- 7.5 Thioredoxin Mechanism of Action -- 7.6 Control of Grx Expression -- 7.7 Control of Trx Expression in Mammalian Systems -- 7.8 Cellular Functions of Grx -- 7.9 Cellular Functions of Trx -- 7.10 Reversible Sulfhydryl Oxidation and Disease -- 7.11 Conclusions -- References -- 8 METHIONINE SULFOXIDE REDUCTASES: A PROTECTIVE SYSTEM AGAINST OXIDATIVE DAMAGE -- 8.1 Introduction -- 8.2 History of the Msr System -- 8.3 MsrA and MsrB Protein Structure and Mechanism of Action -- 8.4 Msr Reducing Requirement -- 8.5 Other Members of the Msr Family -- 8.6 The Msr System: Both a Repair Enzyme and a Scavenger of ROS -- 8.7 Genetic Studies on the Role of the Msr System in Protecting Cells Against Oxidative Damage -- 8.8 Evidence that Oxidative Damage is a Major Factor in Aging: Role of Mitochondria and the Msr System -- 8.9 How can the Msr System be Utilized for Drug Development? -- 8.10 Methionine Sulfoxide and Disease -- Acknowledgment -- References -- IV BIOACTIVITY OF GSH AND SULFUR AMINO ACIDS AS REGULATORS OF CELLULAR PROCESSES -- 9 REGULATION OF PROTEIN FUNCTION BY GLUTATHIONYLATION -- 9.1 Introduction -- 9.2 Glutathione and Redox Regulation in Immunity -- 9.3 Protein Cysteine Oxidation.

9.4 Mechanisms for PSSG Formation and the Complex Scenario of Protein Glutathionylation -- 9.5 Deglutathionylation -- 9.6 Identification of Proteins Undergoing Glutathionylation -- 9.7 Functional Consequences of Protein Glutathionylation -- 9.8 Structural Changes Induced by Protein Glutathionylation -- 9.9 Conclusions -- References -- 10 GSH, SULFUR AMINO ACIDS, AND APOPTOSIS -- 10.1 Introduction -- 10.2 Synthesis and Functions of GSH -- 10.3 Apoptosis: A Programmed Mode to Die -- 10.4 Role of GSH and Cysteine in Apoptosis -- 10.5 Sulfur Amino Acids in Apoptosis -- 10.6 Concluding Remarks and Recent Progress -- Acknowledgments -- References -- 11 METHIONINE OXIDATION: IMPLICATION IN PROTEIN REGULATION, AGING, AND AGING-ASSOCIATED DISEASES -- 11.1 Introduction -- 11.2 The Methionine Sulfoxide Reductase System -- 11.3 Methionine Sulfoxide Reductase and Selenium -- 11.4 Methionine Sulfoxide Reductase: A Knockout Mouse as a Model for Neurodegenerative Diseases -- 11.5 Regulation of Protein Expression/Function by the Methionine Sulfoxide Reductase System -- 11.6 Conclusions -- References -- 12 SULFUR AMINO ACIDS, GLUTATHIONE, AND IMMUNE FUNCTION -- 12.1 The Biochemistry of Sulfur Amino Acids -- 12.2 Sulfur Amino Acid and Glutathione Metabolism Following Infection and Injury -- 12.3 Glutathione and the Immune System -- 12.4 Mechanism of the Effect of Oxidants and Antioxidants on Inflammation and Immune Function -- 12.5 Strategies for Modulating Tissue Glutathione Content and Influencing Immune Function -- 12.6 Taurine and Immune Function -- 12.7 Conclusions -- References -- V GSH AND SULFUR AMINO ACIDS IN PATHOLOGICAL PROCESSES -- 13 SULFUR AMINO ACID DEFICIENCY AND TOXICITY: RESEARCH WITH ANIMAL MODELS -- 13.1 Introduction -- 13.2 Sulfur Amino Acid Deficiency -- 13.3 Sulfur Amino Acid Toxicity -- References.

14 HUMAN PATHOLOGIES AND ABERRANT SULFUR METABOLISM -- 14.1 Introduction -- 14.2 Biosynthesis and Metabolism of Methionine and Cysteine -- 14.3 Defects in the Transulfuration Pathway -- 14.4 Inherited Defects in Membrane Transport -- 14.5 Pathologies Associated with Folic Acid Metabolizing Enzymes -- 14.6 Heterogeneity of GSH Metabolizing Enzymes and Associated Human Pathologies -- References -- 15 INBORN ERRORS OF GSH METABOLISM -- 15.1 Introduction -- 15.2 Definitions -- 15.3 The γ-Glutamyl Cycle -- 15.4 Inborn Errors in the Metabolism of GSH -- 15.5 Animal Models -- Acknowledgments -- References -- 16 HOMOCYSTEINE METABOLISM AND PATHOLOGICAL IMPLICATIONS: THE HOMOCYSTEINE THIOLACTONE HYPOTHESIS OF VASCULAR DISEASE -- 16.1 Introduction -- 16.2 An Overview of Hcy Metabolism -- 16.3 Toxicity of Hcy and Its Metabolites -- 16.4 Physical-Chemical Properties of Hcy-Thiolactone -- 16.5 The Mechanism of Hcy-Thiolactone Biosynthesis -- 16.6 Structural and Functional Consequences of Protein Modification by Hcy-Thiolactone -- 16.7 The Hcy-Thiolactone Hypothesis of Vascular Disease -- 16.8 Pathophysiologic Consequences of Protein N-Homocysteinylation -- 16.9 Urinary Elimination of Hcy-Thiolactone -- 16.10 Enzymatic Elimination of Hcy-Thiolactone -- 16.11 Conclusions -- References -- 17 HOMOCYSTEINE AND CARDIOVASCULAR DISEASE -- 17.1 Introduction -- 17.2 Homocysteine Metabolism -- 17.3 Homocysteine Forms In Vivo -- 17.4 Homocysteine Measurement -- 17.5 Causes of Hyperhomocysteinemia -- 17.6 Therapeutic Options for Lowering Elevated Homocysteine -- 17.7 Epidemiologic Evidence Linking Homocysteine and Atherothrombotic Vascular Disease -- 17.8 Homocysteine and Atherothrombosis: Pathophysiologic Mechanisms -- 17.9 Impact of Homocysteine-Lowering Therapy on Atherothrombotic Vascular Disease -- 17.10 Conclusions -- References.

18 HOMOCYSTEINE AND NEUROLOGICAL DISORDERS -- 18.1 Introduction -- 18.2 What is an "Abnormal" Plasma Homocysteine Level in Clinical Studies of Neurological Disease? -- 18.3 Elevated Plasma Homocysteine and the Risk of Carotid Atherosclerosis -- 18.4 Hyperhomocysteinemia and the Risk of Stroke -- 18.5 Elevated Plasma Homocysteine Levels are Associated with the Risk of Dementia and Alzheimer's Disease -- 18.6 Parkinson's Disease -- 18.7 Epilepsy -- 18.8 Conclusions -- 18.9 Acknowledgments -- References -- 19 GLUTATHIONE, SULFUR AMINO ACIDS, AND CANCER -- 19.1 Introduction -- 19.2 Carcinogenesis, Tumor Growth, and Cell Death -- 19.3 Intercellular and Interorgan Transport of GSH in Tumor-Bearing Mammals -- 19.4 GSH and the Interaction of Metastatic Cells with the Vascular Endothelium -- 19.5 Adaptive Response in Invasive Cells -- 19.6 GSH Depletion and the Sensitization of Cancer Cells to Therapy -- References -- VI GSH AND SULFUR AMINO ACIDS AS DRUGS AND NUTRACEUTICALS -- 20 GSH, GSH DERIVATIVES, AND ANTIVIRAL ACTIVITY -- 20.1 Introduction -- 20.2 Intracellular GSH Status during Viral Infection -- 20.3 Mechanism of Virus-Induced GSH Depletion -- 20.4 Role of Constitutive GSH Levels in Controlling Cell Susceptibility to Viral Infection -- 20.5 Effect of Intracellular GSH Depletion on Viral Replication -- 20.6 Effect of Exogenous GSH and GSH Derivatives on Viral Replication -- 20.7 In Vivo Effects of Systemic and Topic GSH Administration -- References -- 21 N-ACETYL CYSTEINE AND CYTOPROTECTIVE EFFECTS AGAINST BRONCHOPULMONARY DAMAGE: FROM IN VITRO STUDIES TO CLINICAL APPLICATION -- 21.1 Introduction -- 21.2 Oxidative Stress in COPD -- 21.3 Pharmacology of N-Acetylcysteine -- 21.4 Pulmonary Antioxidant and Anti-Inflammatory Effects -- 21.5 Nonpulmonary Effects -- 21.6 Clinical Efficacy of N-Acetylcysteine in COPD -- 21.7 Idiopathic Pulmonary Fibrosis.

21.8 Other Disorders.