By D. J. Clarke, B. Burchell (auth.), Professor Frederick C. Kauffman Ph.D. (eds.)
Advances in molecular biology describing very important enzyme structures taken with drug conjugation and deconjugation reactions and up to date paintings indicating the significance of drug and xenobiotic conjugates as delivery sorts of biologically energetic compounds are reviewed comprehensively. half One describes molecular occasions linked to the expression and rules of transferases and hydrolases enthusiastic about section II drug conjugation and deconjugation. half offers with the legislation of section II conjugation, and half 3 experiences seriously the significance of drug conjugates in pharmacology and toxicology. This quantity is an updated resource of knowledge in this subject and should be of vast curiosity to pharmacologists and toxicologists.
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Additional resources for Conjugation—Deconjugation Reactions in Drug Metabolism and Toxicity
1981). Carbamazepine also induces valproic acid glucuronidation (PANESAR et al. 1989). 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.
III). There has been much speculation regarding how such proteins might be biosynthesised (SATO et aI. 1990; RITTER et al. 1991; WOOSTER et al. 1991) due to their unusual structure. Recently, RITTER et al. (1992b) have isolated a large gene complex of approximately 95 kb that encodes several UGTI family isoforms. Examination of the structure of this complex indicated that it was composed of at least six alternative isoform specific exons, three of which have been identified as those that encode the variable regions of the bilirubin UDPGTs (UGT1 *1 and UGTl *4) and the planar phenol (UDPGT1 *6).
1991) and chromosome 5 (KRASNEWICH et aI. 1987), respectively, which are known to have syntenic regions with the aforementioned human chromosomes (NADEAU and REINER 1989). E. Factors Affecting Uridine Diphosphate GlucuronosyItransferase Expression I. Ontogeny One of the major factors that affects UDPGT expression and hence glucuronidation reactions is ontogeny. Extensive studies on rats have demonstrated that there are three distinct developmental "clusters". The late fetal cluster of UDPGT activities towards simple planar phenols (4~nitrophenol, 2-aminophenol, I-naphthol) develop immediately prior to birth and surge to maximum levels at about 2 days post partum.
Conjugation—Deconjugation Reactions in Drug Metabolism and Toxicity by D. J. Clarke, B. Burchell (auth.), Professor Frederick C. Kauffman Ph.D. (eds.)