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Enzymatic Basis of Detoxication Volume 1 - 1st Edition - ISBN: 9780123800015, 9780323137980

Enzymatic Basis of Detoxication Volume 1

1st Edition

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Author: William B. Jakoby
eBook ISBN: 9780323137980
Imprint: Academic Press
Published Date: 28th October 1980
Page Count: 415
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Enzymatic Basis of Detoxication, Volume I focuses on the catalytic mechanisms and physiological expression of the enzymes that are involved in the detoxication of foreign compounds. The book explores foreign compound metabolism at the level of what specific enzymes can do. This book is organized into three sections and comprised of 17 chapters. The discussion begins with an overview of detoxication and covers both catalytic and non-catalytic removal of foreign substances, along with the general properties of the enzymes that are active in detoxication. The reader is then introduced to the physiological aspects of detoxication, paying particular attention to the kinetic aspects of metabolism and elimination of foreign compounds in animals, human genetic variation in detoxication enzymes, and how such enzymes are induced. The next section focuses on mixed function oxygenase systems and includes chapters on cytochrome P-450 and the detoxication reactions it catalyzes. The book also considers other oxidation-reduction systems, with reference to alcohol dehydrogenase, aldehyde reductase, aldehyde oxidizing enzymes, ketone reductases, xanthine oxidase and aldehyde oxidase, glutathione peroxidase, and superoxide dismutases. The final chapter is devoted to monoamine oxidase, its properties, substrate specificity, inhibitors, kinetics and mechanism, and multiple forms. Pharmacologists, toxicologists, and biochemists will find this book extremely helpful.

Table of Contents

List of Contributors


Contents of Volume II

Chapter 1 Detoxication Enzymes

I. Detoxication

II. Characterization of the Enzymes of Detoxication

III. The Question of Natural Substrate 5 References


Chapter 2 Kinetic Aspects of Metabolism and Elimination of Foreign Compounds in Animals

I. Introduction

II. Pharmacokinetic Model

III. Comments


Chapter 3 Human Genetic Variation in the Enzymes of Detoxication

I. Introductory Remarks

II. Classification of Human Pharmacogenetic Disorders

III. Avenues for Future Exploration

IV. Comments


Chapter 4 Induction of the Enzymes of Detoxication

I. Introduction

II. Induction of Mixed Function Oxidases

III. Chromatin Activation

IV. Effects on RNA Polymerase

V. Effects on Components on Protein Synthesis

VI. Comments


Chapter 5 Comparative Aspects of Detoxication in Mammals

I. Introduction

II. The Origins of Species Differences in Foreign Compound Metabolism

III. Do "Species Patterns" of Foreign Compound Metabolism Exist?

IV. The Significance of the Comparative Biochemistry of Foreign Compounds for Animal Taxonomy

V. The Enzymatic Basis of Species Differences in Foreign Compound Metabolism

VI. Comments


Part II. Mixed Function Oxygenase Systems

Chapter 6 Microsomal Cytochrome P-450: A Central Catalyst in Detoxication Reactions

I. Introduction

II. Purification Procedures

III. Enzyme Assays

IV. Characterization of Purified Enzymes

V. Substrate Specificity

VI. Summary and Comments on Factors Controlling Activities of Cytochrome P-450


Chapter 7 Reactions Catalyzed by the Cytochrome P-450 System

I. Introduction

II. Criteria Used to Establish the Involvement of Cytochrome P-450 in Various Reactions

III. Oxidative Reactions

IV. Reductive Reactions

V. Comments


Chapter 8 The Role of NADPH-Cytochrome c (P-450) Reductase in Detoxication

I. Introduction

II. Microsomal Electron Transport Systems

III. Purification of NADPH-Cytochrome c (P-450) Reductase

IV. Properties of NADPH-Cytochrome c (P-450) Reductase from Various Organs and Species

V. Specificity of Reductase-Cytochrome P-450 Interaction in Various Monooxygenase Reactions; Other Metabolic Functions

Chapter 9 Microsomal Flavin-Containing Monooxygenase: Oxygenation of Nucleophilic Nitrogen and Sulfur Compounds

I. Introduction

II. Hog Liver Microsomal Flavin-Containing Monooxygenase

III. Species and Tissue Distribution


Part III. Other Oxidation-Reduction Systems

Chapter 10 Alcohol Dehydrogenase

I. Introduction

II. Distribution of Alcohol Dehydrogenase

III. Multiple Molecular Forms of Human Liver Alcohol Dehydrogenase

IV. Purification of Human Liver Alcohol Dehydrogenase

V. Molecular Properties of Human Liver Alcohol Dehydrogenase

VI. Catalytic Properties of Human Liver Alcohol Dehydrogenase

VII. Regulation of Ethanol Metabolism in Man


Chapter 11 Aldehyde Reductase

I. Introduction

II. Distribution of Aldehyde Reductases

III. Purification and Assay

IV. Structural Properties

V. Catalytic Properties


Chapter 12 Aldehyde Oxidizing Enzymes

I. Introduction

II. Aldehyde Dehydrogenases

III. Nonspecific Aldehyde Dehydrogenase

IV. Formaldehyde Dehydrogenase

V. Aldehyde Oxidase

VI. Comments


Chapter 13 Ketone Reductases

I. Introduction

II. Assay

III. Purification

IV. Distribution

V. Specificity and Characterization

VI. Comments


Chapter 14 Xanthine Oxidase and Aldehyde Oxidase

I. Introduction

II. Electron Donor Specificity

III. Electron Acceptor Specificity

IV. Inhibitors

V. Human Enzymes

VI. Relevance to Detoxication

VII. Purification and Assay

VIII. Regulation

IX. Comments


Chapter 15 Superoxide Dismutases: Detoxication of a Free Radical

I. Introduction

II. Intermediates of Oxygen Reduction

III. O2- as Substrate

IV. Superoxide Dismutase—The Enzyme

V. The Physiological Role of Superoxide Dismutases


Chapter 16 Glutathione Peroxidase

I. Introduction

II. The Role of Glutathione Peroxidase in Hydroperoxide Metabolism

III. Determination of Glutathione Peroxidase Activity and Definition of Units

IV. Purification

V. Physical and Chemical Properties

VI. Kinetic Data

VII. Active Site, Structure, and Mechanism of Catalysis

VIII. Distribution of Glutathione Peroxidase

IX. Comments


Chapter 17 Monoamine Oxidase

I. Introduction

II. Assay and Purification

III. Substrate Specificity

IV. Properties of the Enzyme

V. Inhibitors

VI. Kinetics and Mechanism

VII. Multiple Forms



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© Academic Press 1980
28th October 1980
Academic Press
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About the Author

William B. Jakoby

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