Metabolic Basis of Detoxication: Metabolism of Functional Groups considers the possible fates of the relatively circumscribed number of functional groups that xenobiotics bear. An understanding of the possible reactions, and the chemical and biological factors influencing them, will contribute to the overall predictability of the fate of "real" molecules. This approach attempts to knit together the understanding of metabolic pathways with that of the enzymes that catalyze the specific steps. The book contains 18 chapters and begins with a discussion of the biological oxidation of carbon atoms. This is followed by separate chapters on the metabolism of halogenated aliphatic hydrocarbons, aryl halides, heterocyclic rings, alcohols, aldehydes, and ketones. Subsequent chapters cover oxidative processes such as metabolic dealkylations and biological oxidation at nitrogen centers; the reduction of nitro and azo compounds and tertiary amine N-oxides; the oxidation, alkylation, acylation, and glycosylation of mercaptans; epoxide metabolism; and conjugation of phenols. The book aims to inform and interest the pharmacologist and toxicologist concerning the biochemical aspects and to orient the biochemist to the pharmacological insights required in dealing with the metabolism of xenobiotics.

Table of Contents:
ContributorsPrefaceIntroduction Text1. Oxidation of Foreign Compounds at Carbon Atoms I. Introduction II. Enzymes Involved in Foreign Compound Oxidation at Carbon Atoms III. Cytochrome P-450-Catalyzed Reactions IV. Examples of Oxidation Reactions at Carbon V. Factors That Affect the Rate and Site of Oxidation at Carbon References2. Aliphatic Halogenated Hydrocarbons I. Introduction II. Chemistry of the Carbon-Halogen Bond III. Metabolic Reactions References3. Aryl Halides I. Introduction II. Halogenated Benzenes III. Halogenated Biphenyls IV. Halogenated Naphthalenes V. Comments References4. Oxidative Metabolism of Heterocyclic Ring Systems I. Introduction II. Nitrogen Heterocycles III. Sulfur Heterocycles IV. Oxygen Heterocycles References5. Alcohols, Aldehydes, and Ketones I. Introduction II. Interconversion of Primary Alcohols and Aldehydes III. Oxidation of Aldehydes IV. Interconversion of Secondary Alcohols and Ketones V. Reduction of Ketones VI. Comments References6. N-Dealkylation and Deamination I. Introduction and Definitions II. Chemical Reactions Leading to C—? Bond Cleavages III. Enzymes Promoting C—? Bond Cleavages IV. Distinctions between Alternative Mechanisms of Enzymatic C—? Bond Cleavage V. Properties of Substrates for N-Dealkylation VI. Metabolic Significance and Pharmacological Consequences of N-Dealkylation References7. Oxidation at Nitrogen Centers I. Introduction II. Chemical Aspects of Nitrogen Oxidation III. Biochemical Aspects of Nitrogen Oxidation IV. Enzyme Systems Involved in Metabolic Nitrogen Oxidation V. Role of Nitrogen Oxidation in the Detoxication and Toxication of Xenobiotics References8. Reductive Metabolism of Nitrogen-Containing Functional Groups I. Introduction II. Reduction of Aromatic Nitro Groups III. Reduction of Azo Compounds IV. Tertiary Amine N-Oxide Reduction V. Factors Affecting Nitro, Azo, and TV-Oxide Reductions VI. Toxicological and Clinical Implications of the Biological Reduction of Organic Nitrogen References9. Functional Groups Bearing Sulfur I. Introduction II. Biotransformation of Functional Groups Bearing Sulfur III. Identification of Toxic Metabolites References10. Mercaptans I. Introduction II. Oxidation of Mercaptans III. Alkylation of Mercaptans IV. Acylation of Mercaptans V. Glycosylation of Mercaptans VI. Integrative Aspects of the Metabolism of Mercaptans References11. Metabolism of Epoxides I. Introduction II. Chemistry of Epoxides III. In Vitro Epoxide Metabolism IV. Comments References12. Hydrolysis of Carboxylic Esters and Amides I. Susceptibility of Carboxyl Esters and Amides to Hydrolysis II. Hydrolytic Detoxication of Esters and Amides In Vivo III. Hydrolytic Toxications and Bioactivations References13. Conjugation of Phenols I. Chemistry of the Phenolic Hydroxy 1 Group II. Inventory of Substrates III. Factors Determining Conjugation In Vivo and in Isolated Cell Preparations IV. Inhibition of Conjugation In Vivo and in Isolated Cell Preparations References14. Conjugation of Xenobiotic Carboxylic Acids I. Introduction II. The Carboxylic Acid Group III. Decarboxylation IV. Reduction V. Conjugation with Glucuronic Acid VI. Conjugations with Sugars VII. Conjugations with Amino Acids VIII. Methyl Ester Formation IX. Amide Formation X. Elimination Unchanged XI. Chemical and Biological Factors Governing the Relative Extents of Glucuronic Acid and Amino Acid Conjugations of an Acid XII. Consequences of the Conjugation of Carboxylic Acids References15. Conjugation Reactions of Nitrogen Centers I. Carbamate Formation II. Acylation Reactions III. Sulfation at Nitrogen IV. Sugar Conjugations at Nitrogen V. N-Methylation VI. Concluding Remarks References16. Metabolism of Organic Hydroperoxides I. Introduction II. Chemical and Physical Properties of Organic Hydroperoxides III. Enzymatic Basis for Organic Hydroperoxide Reduction IV. Antioxidants V. Assessment of Hydroperoxide Status in Metabolic Systems References17. Role of the Intestinal Microflora I. Description of the Flora II. Some of the Detoxication Reactions of the Flora III. The Flora in Health and Disease IV. Comment References18. Metabolism and Urinary Excretion I. Introduction II. Renal Function III. Examples of Interaction of Metabolism and Urinary Excretion IV. Comments ReferencesIndex