By D. J. Clarke, B. Burchell (auth.), Professor Frederick C. Kauffman Ph.D. (eds.)
Advances in molecular biology describing very important enzyme structures enthusiastic about drug conjugation and deconjugation reactions and up to date paintings indicating the significance of drug and xenobiotic conjugates as shipping sorts of biologically energetic compounds are reviewed comprehensively. half One describes molecular occasions linked to the expression and legislation of transferases and hydrolases thinking about part II drug conjugation and deconjugation. half bargains with the law of section II conjugation, and half 3 reports severely the significance of drug conjugates in pharmacology and toxicology. This quantity is an up to date resource of data in this subject and should be of huge curiosity to pharmacologists and toxicologists.
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16 CLARKE and B. BURCHELL Eight different rat UDPGTs and ten human UDPGTs have been identified to date (BURCHELL et al. 1991) by cDNA cloning. Tables 2 and 3 show the extent of our current knowledge of the heterogeneity of UDPGTs in rat and human liver, respectively, derived from purification and cloning studies. II. Primary Structure and Post-Translational Processing of Uridine Diphosphate Glucuronosyltransferases Studies on the primary sequence of UDPGTs has revealed a number of important features regarding UDPGTs.
The most direct approach towards determining the heterogeneity of UDPGTs has been the physical separation of UDPGTs by protein purification and cloning and expression of individual enzyme forms. Purification of UDPGTs proved to be inherently difficult due to their relative instability in the high concentrations of detergent required for Cytoplasm Lumen Fig. 2. ) membrane. UDPGA, uridine 5'-diphosphoglucuronate The Uridine Diphosphate Glucuronosyltransferase Multigene Family 11 solubilisation (see BURCHELL 1981 for a review of earlier studies), their phospholipid dependence (GRAHAM and WOOD 1969; GRAHAM et al.
Co-administration of phenobarbitone and phenytoin induces chloramphenicol glucuronidation (BLOXHAM et al. 1979; POWELL et al. 1981). Several oral contraceptive drugs have been demonstrated to increase the glucuronidation of paracetamol (ABERNETHY et al. 1982; MINERS et al. 1983; MITCHELL et al. 1983), clofibric acid (MINERS et al. 1984b), temazepam (STOEHR et al. 1984), salicylic acid (MINERS et al. 1986), diflusinal (MACDoNALD et al. 1990) and phenoprocoumon (MONIG et al. 1990). Rifampicin and sulfinpyazone have also been reported to induce paracetamol glucuronidation (BOCK et al.