Archives of toxicology
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Archives of toxicology · Nov 2011
Comparative StudyEffect of UDP-glucuronosyltransferase 2B15 polymorphism on bisphenol A glucuronidation.
Bisphenol A (BPA) is one of a number of 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 in Caucasian, African-American, Hispanic, and Oriental populations to date. In this study, the effects of amino acid substitutions in UGT2B15 on BPA glucuronidation were studied using recombinant UGT2B15 enzymes of wild-type (UGT2B15.1) and all identified variants (UGT2B15.2, UGT2B15.3, UGT2B15.4, UGT2B15.5, UGT2B15.6, and UGT2B15.7) expressed in insect (Sf9) cells. ⋯ However, the K (m), V (max), and CL (int) values of UGT2B15.3, UGT2B15.4, UGT2B15.6, and UGT2B15.7 having L86S, T352I, and/or K523T substitution(s) for BPA glucuronidation were comparable to those of UGT2B15.1. These findings suggest that D85Y substitution in UGT2B15 decreases enzymatic function and that the polymorphic alleles of UGT2B15 are closely associated with variations in the metabolism and toxicity of BPA. The information gained in this study should help with in vivo extrapolation to assess the toxicity of endocrine-disrupting chemicals.