caa a22 4500 445854073 CHVBK 20180317145423.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00204-011-0690-5 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0690-5 Effect of UDP-glucuronosyltransferase 2B15 polymorphism on bisphenol A glucuronidation [Elektronische Daten] [Nobumitsu Hanioka, Hiroyuki Oka, Kenjiro Nagaoka, Shinichi Ikushiro, Shizuo Narimatsu] 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. The K m, V max, and CL int values of UGT2B15.1 for BPA glucuronidation were 3.9μM, 650pmol/min/mg protein, and 170μL/min/mg protein, respectively. Although there is no significant difference in the K m value between wild-type and any variant UGT2B15, the V max and CL int values of UGT2B15 variants having D85Y substitution were markedly reduced to 14 and 10% for UGT2B15.2, and 4.3 and 3.9% for UGT2B15.5 compared with those of UGT2B15.1, respectively. 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. Springer-Verlag, 2011 Bisphenol A nationallicence Glucuronidation nationallicence UDP-glucuronosyltransferase 2B15 (UGT2B15) nationallicence Genetic polymorphism nationallicence Hanioka Nobumitsu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, 700-8530, Kita-ku, Okayama, Japan aut Oka Hiroyuki Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, 700-8530, Kita-ku, Okayama, Japan aut Nagaoka Kenjiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, 700-8530, Kita-ku, Okayama, Japan aut Ikushiro Shinichi Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, 939-0398, Imizu, Toyama, Japan aut Narimatsu Shizuo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, 700-8530, Kita-ku, Okayama, Japan aut Archives of Toxicology Springer-Verlag 85/11(2011-11-01), 1373-1381 0340-5761 85:11<1373 2011 85 204 https://doi.org/10.1007/s00204-011-0690-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0690-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hanioka Nobumitsu Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, 700-8530, Kita-ku, Okayama, Japan aut NATIONALLICENCE 700 1- Oka Hiroyuki Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, 700-8530, Kita-ku, Okayama, Japan aut NATIONALLICENCE 700 1- Nagaoka Kenjiro Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, 700-8530, Kita-ku, Okayama, Japan aut NATIONALLICENCE 700 1- Ikushiro Shinichi Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, 939-0398, Imizu, Toyama, Japan aut NATIONALLICENCE 700 1- Narimatsu Shizuo Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, 700-8530, Kita-ku, Okayama, Japan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/11(2011-11-01), 1373-1381 0340-5761 85:11<1373 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer