Glutathione Oxidative Stress and Disease Series

This is the first serious attempt to synthesize all that became known of glutathione over the last three decades. The book contains an update of glutathione biosynthesis with special emphasis on its regulation in adaptive stress responses. Other chapters review glutathione transport systems and glutathione peroxidases and their differences in substrate specificities and localization. Further contributions center on the diversified roles of different glutathione-S-transferases and the roles of nitrosoglutathione and glutaredoxins - a subfamily of redoxins. The book closes with discussions of the analogous or homologous thiol metabolism in pathogens and the potential suitability of involved enzymes as drug targets.

Key selling features:

• Summarizing the way glutathione is involved in stress responses



• Compiling the multiple ways glutathione affects inflammatory responses



• Disclosing how glutathione dampens programmed cell death such as ferroptosis



• Exploring the enigma of how enzymes accelerate glutathione-dependent processes



• Discussing how detoxification and redox regulation is mediated by glutathionylation



• Reviewing the ways glutaredoxins catalyze protein disulfide reduction



• Highlighting the medical impact of glutathione-related metabolic pathways



• Illustrating the role thiol metabolism of pathogens might play in drug discovery

Contents

Series Preface.............................................................................................................xi

Editor’s Preface....................................................................................................... xiii

Editor Biography......................................................................................................xix

List of Contributors .................................................................................................xxi

Part I Biosynthesis, Compartmentation,

and Transport of Glutathione

Chapter 1 Biosynthesis of Glutathione and Its Regulation....................................3

Henry Jay Forman, Hongqiao Zhang, and Terrance J. Kavanagh

Chapter 2 Renal Glutathione Transport Systems: Roles in Redox

Homeostasis, Cytoprotection, and Bioactivation................................ 35

Lawrence H. Lash

Part II Glutathione-Dependent

Hydroperoxide Metabolism

Chapter 3 The Catalytic Mechanism of Glutathione Peroxidases....................... 53

Laura Orian, Giorgio Cozza, Matilde Maiorino, Stefano

Toppo, and Fulvio Ursini

Chapter 4 GPx1-Dependent Regulatory Processes in Health and Disease......... 67

Diane E. Handy and Joseph Loscalzo

Chapter 5 Glutathione Peroxidase 1 as a Modulator of Insulin Production

and Signaling: Implications for Its Dual Role in Diabetes................. 81

Holger Steinbrenner and Lars-Oliver Klotz

Chapter 6 GPx2 Role in Physiology and Carcinogenesis....................................95

Anna P. Kipp

Chapter 7 GPx4: From Prevention of Lipid Peroxidation to

Spermatogenesis and Back................................................................ 111

Matilde Maiorino, Antonella Roveri, and Fulvio Ursini

Chapter 8 Thiols, Glutathione, GPx4, and Lipid Metabolism at the

Crossroads of Cell Death and Survival............................................. 129

José Pedro Friedmann Angeli, Valerian E. Kagan, and Marcus

Conrad

Chapter 9 Peroxiredoxin 6 as Glutathione Peroxidase...................................... 143

Yefim Manevich

Chapter 10 Glutathione Peroxidases and the Thyroid Gland.............................. 161

Lutz Schomburg

Part III Conjugations and Isomerizations

Chapter 11 Glutathione Transferases: From the Test Tube to the Cell................ 175

Bengt Mannervik and Birgitta Sjödin

Chapter 12 Protein S-glutathionylation and Glutathione S-transferase P............ 201

Kenneth D. Tew

Chapter 13 The Role of Glutathione in Biosynthetic Pathways and

Regulation of the Eicosanoid Metabolism........................................ 215

Ralf Morgenstern, Leopold Flohé, Jesper Z. Haeggström, and

Per-Johan Jakobsson

Chapter 14 Nitric Oxide and S-Nitrosoglutathione..............................................227

Iain L. O. Buxton and Scott D. Barnett

Part IV The Glutaredoxins

Chapter 15 The Catalytic Mechanism of Glutaredoxins..................................... 251

Linda Liedgens and Marcel Deponte

Chapter 16 The Role of Glutaredoxins in the Brain............................................263

Carsten Bernd, Anna Dorothee Engelke, Klaudia Lepka, and

Lars Bräutigam

Part V Glutathione Derivatives and

Substitutes in Pathogenic Microorganisms

Chapter 17 Biosynthesis of Polyamine–Glutathione Derivatives in

Enterobacteria and Kinetoplastida...................................................285

Marcelo A. Comini

Chapter 18 Trypanothione Functions in Kinetoplastida......................................307

Martín Hugo, Madia Trujillo, Lucía Piacenza, and Rafael Radi

Chapter 19 Mycothiol, a Low-Molecular-Weight Thiol Drafted for

Oxidative Stress Defense Duty......................................................... 331

Leonardo Astolfi Rosado, Brandán Pedre, and Joris Messens

Chapter 20 Biosynthesis and Functions of Bacillithiol in Firmicutes................. 357

Quach Ngoc Tung, Nico Linzner, Vu Van Loi,

and Haike Antelmann

Index....................................................................................................................... 379

Leopold Flohé is Professor at the Universidad de la Republica Uruguay in Montevideo, Uruguay. He also Distinguishing Visiting Professor in the Department of Molecular Medicine at the University of Padova in Italy. He has been recognized by PubMed.gov as a Redox Pioneer because has published an article on antioxidant/redox biology, as first author, that has been cited more than 1,000 times, and more than 20 articles have been cited more than 100 times. He obtained the medical doctorate at the Institute of Pharmacology and Toxicology at the University of Tübingen, Germany, in 1968. He held positions in both Academia (Tübingen, Aachen, and Braunschweig, Germany) and industry (Aachen). He is now operating the biotech company MOLISA in Magdeburg, Germany, while teaching as guest professor at the local university. Dr. Flohé is the pioneer who established the selenoprotein nature of glutathione peroxidase (GPx), the first and, for almost 10 years, the only selenoprotein known in animals. His work was pivotal to link the essential trace element selenium to metabolic processes, which led the Food and Drug Administration (FDA) to approve selenium supplementation for humans in 1980, and stimulated selenium biochemistry in general. In recent years, he embarked on investigating how pathogens protect themselves from oxidative killing. His studies on the thiol-dependent hydroperoxide metabolism of trypanosomatids and mycobacteria defined molecular drug targets, paving the way to new therapeutic strategies for neglected diseases affecting the people of developing countries.