Effect of UDP-glucuronosyltransferase 2B15 polymorphism on bisphenol A glucuronidation.
作者： Nobumitsu Hanioka , Hiroyuki Oka , Kenjiro Nagaoka , Shinichi Ikushiro , Shizuo Narimatsu
DOI: 10.1007/S00204-011-0690-5
关键词:
摘要: Bisphenol A (BPA) is one of a number potential endocrine-disrupting chemicals, which are metabolized mainly by UDP-glucuronosyltransferase 2B15 (UGT2B15) in humans. Six UGT2B15 allelic variants (UGT2B15*2, UGT2B15*3, UGT2B15*4, UGT2B15*5, UGT2B15*6, and UGT2B15*7; wild-type, UGT2B15*1) with amino acid substitutions have been found Caucasian, African-American, Hispanic, Oriental populations to date. In this study, the effects on BPA glucuronidation were studied using recombinant enzymes wild-type (UGT2B15.1) all identified (UGT2B15.2, UGT2B15.3, UGT2B15.4, UGT2B15.5, UGT2B15.6, UGT2B15.7) expressed insect (Sf9) cells. The K m, V max, CL int values UGT2B15.1 for 3.9 μM, 650 pmol/min/mg protein, 170 μL/min/mg respectively. Although there no significant difference m value between any variant UGT2B15, max having D85Y substitution markedly reduced 14 10% UGT2B15.2, 4.3 3.9% UGT2B15.5 compared those UGT2B15.1, However, UGT2B15.7 L86S, T352I, and/or K523T substitution(s) comparable UGT2B15.1. These findings suggest that decreases enzymatic function polymorphic alleles closely associated variations metabolism toxicity BPA. information gained study should help vivo extrapolation assess chemicals.
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