Metabolic Basis of Detoxication - 1st Edition - ISBN: 9780123800602, 9780323137997

Metabolic Basis of Detoxication

1st Edition

Metabolism of Functional Groups

Authors: William B. Jakoby
eBook ISBN: 9780323137997
Imprint: Academic Press
Published Date: 28th June 1982
Page Count: 375
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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





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




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© Academic Press 1982
Academic Press
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About the Author

William B. Jakoby

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