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 types of biologically energetic compounds are reviewed comprehensively. half One describes molecular occasions linked to the expression and law of transferases and hydrolases concerned with part II drug conjugation and deconjugation. half bargains with the rules of section II conjugation, and half 3 stories significantly 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 extensive curiosity to pharmacologists and toxicologists.
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Additional info for Conjugation—Deconjugation Reactions in Drug Metabolism and Toxicity
The proposed uridine diphosphate (UDP)-binding site in UDP-glucuronosyltransferases (UDPGTs) based on a region of high amino acid identity with UDPglucosyltransferases (ugt). The predicted amino acid sequence corresponding to residues 352-403 of human phenol UDPGT (UGTl *6) was compared to that of other UDPGTs and ugts. The boxed areas indicate regions of conservative amino acid replacements between the ten proteins. The reader is referred to the following references describing each of the DNA sequences encoding these proteins: human UGT1 *6 (HARDING et al.
F" Signal sequence , _____ Conserved domain _ _ _.... Aglycone binding domain UDP-sugar binding domain Glycosylation sites Transmembrane domain E. R. retention signal Fig. 5. Functional domains on a linearised uridine diphosphate (UDP) glucuronosyltransferase protein map. , endoplasmic reticulum The Uridine Diphosphate Glucuronosyltransferase Multigene Family 19 III. Substrate Specificity of Uridine Diphosphate Glucuronosyltransferase Isoforms Studies on the substrate specificity of individual UDPGT isoforms has been achieved by either assaying purified UDPGT proteins or whole cell extracts derived from tissue culture cells expressing single UDPGT cDNA clones.
Biochem Biophys Rec Commun 173:1001-1007 Franz PM, Anliker SL, Callahan IT, DeSante KA, Dhahir PH, Nelson RL, Rubin A (1990) Disposition in humans of racemic picenadol, an opioid analgesic. Drug Metab Dispos 18:968-973 Fraser AD, Bryan W, Isner AF (1991) Urinary screening for alprazolam and its major metabolites by the Abbot ADx and TDx analysers with confirmation by GCIMS. J Anal ToxicoI15:25-29 Gervasi PG, Longo V, Naldi F, Panattoni G, Ursino F (1991) Xenobiotic-metabolising enzymes in human respiratory nasal mucosa.
Conjugation—Deconjugation Reactions in Drug Metabolism and Toxicity by D. J. Clarke, B. Burchell (auth.), Professor Frederick C. Kauffman Ph.D. (eds.)