Hydrolysis in Drug and Prodrug Metabolism: Chemistry, Biochemistry, and Enzymology
Many drugs and other xenobiotics (e.g., preservatives, insecticides, and plastifiers) contain hydrolyzable moieties such as ester or amide groups. In biological media, such foreign compounds are, therefore, important substrates for hydrolytic reactions catalyzed by hydrolases or proceeding non-enzymatically.\ Despite their significance, until now, no book has been dedicated to hydrolysis and hydrolases in the metabolism of drugs and other xenobiotics. This work fills a gap in the literature...
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Xenobiotic metabolism is a subject of broad interdisciplinary, encompassing physiology, pathophysiology, pharmacology, toxicology, environmental issues, biochemistry, genetics, medical chemistry, computational (bio)chemistry, analytical chemistry, etc., and reactions of hydrolysis play a central role in metabolic pathways. Benard Testa is very well-known for his capacity to conceptualize reactions of drug metabolism, and, in this volume, he presents a comprehensive review of all metabolic reactions and enzymes involved in the hydrolysis of drugs and prodrugs. Nothing of this sort has been written before, as hydrolysis together with some other reactions of drug metabolism have long been in the shadow of the drug-metabolism community’s preoccupation with the ‘P450 hype’ and the superfamily of CYP genes coding for oxidative enzymes of drug metabolism. Recent developments, such as peptide drugs or inhibitors of cholinesterases, have lent new importance to these ‘other’ important enzymes of drug metabolism. Bernard Testa’s fundamental knowledge of this field and his commitment to clear conceptualization and precise language make this book, sadly delayed by the untimely death of Joachim Moyer, another important addition to his contributions that help us to understand the principles of xenobiotic biotransformation.
Ch. 1Introduction: Metabolic Hydrolysis and Prodrug DesignCh. 2Classification, Localization, and Some Physiological Roles of Hydrolytic EnzymesCh. 3Catalytic Mechanisms of Hydrolytic EnzymesCh. 4The Hydrolysis of AmidesCh. 5The Hydrolysis of LactamsCh. 6The Hydrolysis of PeptidesCh. 7The Hydrolysis of Carboxylic Acid EstersCh. 8The Hydrolysis of Carboxylic Acid Ester ProdrugsCh. 9The Cleavage of Esters of Inorganic AcidsCh. 10The Hydration of EpoxidesCh. 11Miscellaneous Reactions of Hydration and DehydrationCh. 12Conclusion: The Biochemistry of WaterIndex
