title: Interaction of bisphenol A with human UDP-glucuronosyltransferase 1A6 enzyme.
abstract: The effects of bisphenol A (BPA) on UDP-glucuronosyltransferase 1A6 (UGT1A6) activities in microsomes from human livers and yeast cells expressing human UGT1A6 (humUGT1A6) were investigated. Serotonin (5-HT) and 4-methylumbelliferone (4-MU) were used as the substrates for UGT1A6. BPA dose-dependently inhibited 5-HT and 4-MU glucuronidation activities in both enzyme sources. The IC(50) values of BPA for 5-HT and 4-MU glucuronidation activities were 156 and 163 microM for liver microsomes, and 84.6 and 80.3 microM for yeast cell microsomes expressing humUGT1A6, respectively. The inhibitory pattern of BPA for 5-HT and 4-MU glucuronidation activities in human liver microsomes exhibited a mixture of competitive and noncompetitive components, with K(i) values of 84.9 and 72.3 microM, respectively. In yeast cell microsomes expressing humUGT1A6, 5-HT glucuronidation activities were noncompetitively inhibited by BPA (K(i) value, 65.5 microM), whereas the inhibition of 4-MU glucuronidation activities by BPA exhibited the mixed type (K(i) value, 42.5 microM). These results suggest that BPA interacts with human UGT1A6 enzyme, and that the interaction may contribute to the toxicity, such as hormone disruption and reproductive effects, of BPA.
authors.affiliation: Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Nobumitsu
authors.initials: N
authors.lastname: Hanioka
authors.forename: Yuri
authors.initials: Y
authors.lastname: Takeda
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka-Kagawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Hideto
authors.initials: H
authors.lastname: Jinno
authors.forename: Shizuo
authors.initials: S
authors.lastname: Narimatsu
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds; D005260:Female; D020719:Glucuronides / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006923:Hymecromone / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D010636:Phenols / Q000633:toxicity*; D012701:Serotonin / Q000378:metabolism; D015003:Yeasts; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D020719:Glucuronides; D014453:Glucuronosyltransferase; D006923:Hymecromone; D010636:Phenols; D012701:Serotonin; C110655:UDP-glucuronosyltransferase, UGT1A6; C006780:bisphenol A; D000098826:Bisphenol A Compounds