Enzymatic Basis of Detoxication Volume 1

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.

Contenu

List of Contributors
Preface
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
References
Chapter 2 Kinetic Aspects of Metabolism and Elimination of Foreign Compounds in Animals
I. Introduction
II. Pharmacokinetic Model
III. Comments
References
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
References
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
References
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
References
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
References
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
References
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
References
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
References
Chapter 11 Aldehyde Reductase
I. Introduction
II. Distribution of Aldehyde Reductases
III. Purification and Assay
IV. Structural Properties
V. Catalytic Properties
References
Chapter 12 Aldehyde Oxidizing Enzymes
I. Introduction
II. Aldehyde Dehydrogenases
III. Nonspecific Aldehyde Dehydrogenase
IV. Formaldehyde Dehydrogenase
V. Aldehyde Oxidase
VI. Comments
References
Chapter 13 Ketone Reductases
I. Introduction
II. Assay
III. Purification
IV. Distribution
V. Specificity and Characterization
VI. Comments
References
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
References
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
References
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
References
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
References