Conjugation-Deconjugation Reactions in Drug Metabolism and Toxicity

Advances in molecular biology describing important enzyme systems involved in drug conjugation and deconjugation reactions and recent work indicating the importance of drug and xenobiotic conjugates as transport forms of biologically active compounds are reviewed comprehensively. Part One describes molecular events associated with the expression and regulation of transferases and hydrolases involved in Phase II drug conjugation and deconjugation. Part Two deals with the regulation of Phase II conjugation, and Part Three reviews critically the importance of drug conjugates in pharmacology and toxicology. This volume is an up-to-date source of information on this topic and will be of broad interest to pharmacologists and toxicologists.

Inhalt
Section I: Transferases and Hydrolases Involved in Phase II ConjugationDeconjugation Reactions, Genetic Polymorphism and Regulation of Expression.- 1 The Uridine Diphosphate Glueuronosyltransferase Multigene Family: Function and Regulation With 7 Figures.- 2 Sulfotransferase Enzymes With 6 Figures.- 3 Regulation of Expression of Rat Liver Glutathione S-Transferases: Xenobiotic and Antioxidant Induction of the Ya Subunit Gene With 6 Figures.- 4 Human N-Acetyltransferases With 3 Figures.- 5 Genetic Regulation of the Subcellular Localization and Expression of Glucuronidase With 5 Figures.- 6 Microsomal Amidases and Carboxylesterases With 5 Figures.- 7 O-, N, and S-Methyltransferases With 2 Figures.- Section II: Regulation of Phase II Conjugation: Deconjugation Reactions in Intact Cells and Tissues.- 8 Cofactor Supply as a Rate-Limiting Determinant of Hepatic Conjugation Reactions With 5 Figures.- 9 Regulation of Drug Conjugate Production by Futile Cycling in Intact Cells With 4 Figures.- 10 Pharmacokinetic Modeling of Drug Conjugates With 22 Figures.- 11 Regulation of Drug Conjugate Processing by Hepatocellular Transport Systems With 1 Figure.- Section III: Pharmacology and Toxicology of Drug Conjugates.- 12 Biologically Active Conjugates of Drugs and Toxic Chemicals With 5 Figures.- 13 Acyl Glucuronides as Chemically Reactive Intermediates With 10 Figures.- 14 Roles of Uridine Diphosphate Glucuronosyltransferases in Chemical Carcinogenesis With 9 Figures.- 15 Sulfonation in Chemical Carcinogenesis With 11 Figures.- 16 Glutathione Conjugate-Mediated Toxicities With 8 Figures.- 17 Challenges and Directions for Future Research.