title: Modulation of UDP-glucuronosyltransferase activity by protein-protein association.
abstract: Drug oxidation and conjugation mediated by cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT) have long been considered to take place separately. However, our recent studies have suggested that CYP3A4 specifically associates with UGT2B7 and alters the regioselectivity of morphine glucuronidation. This observation strongly supports the view that there is functional cooperation between P450 and UGT to facilitate multistep drug metabolism. In recent years, accumulating evidence has suggested an interaction between UGT isoforms or between P450 and UGTs and a change in UGT function by protein-protein association. In this review, we summarize these interactions and discuss their relevance to UGT function.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. ishii@phar.kyushu-u.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.forename: Shuso
authors.initials: S
authors.lastname: Takeda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000737:chemistry*; D008862:Microsomes, Liver / Q000201:enzymology; D009020:Morphine / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D000701:Analgesics, Opioid; D004364:Pharmaceutical Preparations; D009020:Morphine; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D014453:Glucuronosyltransferase