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.
Table of Contents
PREFACE.CONTRIBUTORS.
I INTRODUCTION.
1 GLUTATHIONE AND THE SULFUR-CONTAINING AMINO ACIDS: AN OVERVIEW (John T. Brosnan and Margaret E. Brosnan).
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 (Cécile Bos, Jean-François Huneau, and Claire Gaudichon).
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 (Federico V. Pallardó, Jelena Markovic, and José Vinã).
3.1 Introduction.
3.2 Glutathione Content in Cells.
References.
4 INTESTINAL METABOLISM OF SULFUR AMINO ACIDS (Nancy Benight, Douglas G. Burrin, and Barbara Stoll).
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 (Kevin L. Schalinske).
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: ANTIOXIDANTAND CONJUGATION ACTIVITIES (Nils-Erik Huseby, Elisabeth Sundkvist, and Gunbjørg Svineng).
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 (Elizabeth A. Sabens and John J. Mieyal).
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 (Herbert Weissbach and Nathan Brot).
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 (Pietro Ghezzi and Paolo Di Simplicio).
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 (Giuseppe Filomeni, Katia Aquilano, and Maria Rosa Ciriolo).
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 (Jackob Moskovitz and Derek B. Oien).
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 (Robert Grimble).
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 (David H. Baker and Ryan N. Dilger).
13.1 Introduction.
13.2 Sulfur Amino Acid Deficiency.
13.3 Sulfur Amino Acid Toxicity.
References.
14 HUMAN PATHOLOGIES AND ABERRANT SULFUR METABOLISM (Danyelle M. Townsend, Haim Tapiero, and Kenneth D. Tew).
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 (llinor Ristoff).
15.1 Introduction.
15.2 Definitions.
15.3 The y-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 (Hieronim Jakubowski).
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 (Jayanta R. Das and Sanjay Kaul).
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 (Rodica E. Petrea and Sudha Seshadri).
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 (José M. Estrela, Julian Carretero, and Angel Ortega).
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 (Anna Teresa Palamara, Lucia Nencioni, Rossella Sgarbanti, and Enrico Garaci).
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 (Richard Dekhuijzen).
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.
21.9 Conclusions.
References.
22 TAURINE AS DRUG AND FUNCTIONAL FOOD COMPONENT (Ramesh C. Gupta, Massimo D’Archivio, and Roberta Masella).
22.1 Introduction.
22.2 The Unique Character of Taurine: Basis for Distinguished Behavior.
22.3 Functional Properties of Taurine.
22.4 Taurine Deficiency.
22.5 Taurine Concentration in Fetal Development and Neonatal Growth.
22.6 Beneficial Actions of Taurine.
22.7 Taurine and Diabetes.
22.8 Taurine and the Cardiovascular System.
22.9 Taurine and Endothelial Dysfunction.
22.10 Taurine and Lung Dysfunction.
22.11 Taurine and the Kidney.
22.12 Retinal Protection.
22.13 Anticancer Activity of Taurine.
22.14 Taurine in Bone Tissue Formation and Inhibition of Bone Loss.
22.15 Taurine and Smoking.
22.16 Taurine as an Antialcohol Molecule.
22.17 Taurine as Functional Food and Supplement.
22.18 Conclusions.
References.
SUBJECT INDEX.
