Metabolic Basis of Detoxication

Metabolic Basis of Detoxication

Metabolism of Functional Groups

1st Edition - June 28, 1982

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  • Author: William B. Jakoby
  • eBook ISBN: 9780323137997

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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

  • Contributors




    1. 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


    2. Aliphatic Halogenated Hydrocarbons

    I. Introduction

    II. Chemistry of the Carbon-Halogen Bond

    III. Metabolic Reactions


    3. Aryl Halides

    I. Introduction

    II. Halogenated Benzenes

    III. Halogenated Biphenyls

    IV. Halogenated Naphthalenes

    V. Comments


    4. Oxidative Metabolism of Heterocyclic Ring Systems

    I. Introduction

    II. Nitrogen Heterocycles

    III. Sulfur Heterocycles

    IV. Oxygen Heterocycles


    5. 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


    6. N-Dealkylation and Deamination

    I. Introduction and Definitions

    II. Chemical Reactions Leading to C—Ν Bond Cleavages

    III. Enzymes Promoting C—Ν Bond Cleavages

    IV. Distinctions between Alternative Mechanisms of Enzymatic C—Ν Bond Cleavage

    V. Properties of Substrates for N-Dealkylation

    VI. Metabolic Significance and Pharmacological Consequences of N-Dealkylation


    7. 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


    8. 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


    9. Functional Groups Bearing Sulfur

    I. Introduction

    II. Biotransformation of Functional Groups Bearing Sulfur

    III. Identification of Toxic Metabolites


    10. 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


    11. Metabolism of Epoxides

    I. Introduction

    II. Chemistry of Epoxides

    III. In Vitro Epoxide Metabolism

    IV. Comments


    12. 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


    13. 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


    14. 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


    15. 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


    16. 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


    17. 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


    18. Metabolism and Urinary Excretion

    I. Introduction

    II. Renal Function

    III. Examples of Interaction of Metabolism and Urinary Excretion

    IV. Comments



Product details

  • No. of pages: 375
  • Language: English
  • Copyright: © Academic Press 1982
  • Published: June 28, 1982
  • Imprint: Academic Press
  • eBook ISBN: 9780323137997

About the Author

William B. Jakoby

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