Human UDP-glucuronosyltransferase isoforms involved in bisphenol A glucuronidation
Human UDP-glucuronosyltransferase isoforms involved in bisphenol A glucuronidation
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DOI：
10.1016/j.chemosphere.2008.09.053
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发表时间：
2008-12-01
期刊：
影响因子：
8.8
通讯作者：
Narimatsu, Shizuo
中科院分区：
文献类型：
--
作者：
Hanioka, Nobumitsu;Naito, Takanori;Narimatsu, Shizuo
双酚A（BPA）是一种潜在的内分泌干扰物，可能会影响正常的荷尔蒙功能。在这项研究中，使用人肝微粒体和在昆虫细胞中表达的重组人UGT（UGT 1A 1、UGT 1A 3、UGT 1A 4），通过动力学分析研究了参与BPA葡萄糖醛酸化的人UDP-葡萄糖醛酸基转移酶（UGT）亚型。UGT 1A6。UGT 1A 9、UGT 2B 4、UGT 2B 7、UGT 2B 15和UGT 2B 17）。BPA葡萄糖醛酸化由UGT 1A 1、UGT 1A 3、UGT 1A 9、UGT 2B 4、UGT 2B 7和UGT 2B 15以及人肝微粒体催化。在这些UGT中，UGT 2B 15在低（1.0 μ M）和高（20 μ M）底物浓度下显示出最高的BPA葡萄糖醛酸化活性。通过构建Michaelis-Menten和Eadie-Hofstee图进行BPA葡萄糖醛酸化的动力学分析。合并人肝微粒体和UGT 2B 15的BPA葡萄糖醛酸化动力学曲线为双相，合并人肝微粒体的Km和Vmax值分别为6.39 μ M和4250 pmol min（-1）mg（-1）蛋白，UGT 2B 15的Km和Vmax值分别为8.68 μ M和873 pmol min（-1）mg（-1）蛋白。通过合并人肝微粒体和UGT 2B 15进行BPA葡萄糖醛酸化的Km值相似。这些结果表明，BPA主要是葡萄糖醛酸化的UGT 2B 15在人肝微粒体，并建议，这种UGT亚型在BPA的解毒和消除中发挥重要作用。(c)2008爱思唯尔有限公司保留所有权利。
Bisphenol A (BPA) is one of a number of potential endocrine disruptors which may affect normal hormonal function. In this study, human UDP-glucuronosyltransferase (UGT) isoforms involved in BPA glucuronidation were Studied by kinetic analyses using human liver microsomes and recombinant human UGTs expressed in insect cells (UGT1A1, UGT1A3, UGT1A4. UGT1A6. UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17). BPA glucuronidation was catalyzed by UGT1A1, UGT1A3, UGT1A9, UGT2B4, UGT2B7 and UGT2B15 as well as by human liver microsomes. Among these UGTs, UGT2B15 showed the highest activity of BPA glucuronidation at low- (1.0 mu M) and high- (20 mu M) substrate concentrations. Kinetic analyses of BPA glucuronidation were performed by constructing Michaelis-Menten and Eadie-Hofstee plots. The kinetic profile of BPA glucuronidation by pooled human liver microsomes and UGT2B15 was monophasic, the K-m and V-max values were 6.39 mu M and 4250pmol min(-1) mg(-1) protein for pooled human liver microsomes, and 8.68 mu M and 873 pmol min(-1) mg(-1) protein for UGT2B15, respectively. The K-m values for BPA glucuronidation by pooled human liver microsomes and UGT2B15 were similar. These findings demonstrate that BPA is mainly glucuronidated by UGT2B15 in human liver microsomes, and suggest that this UGT isoform plays important roles in the detoxification and elimination of BPA. (c) 2008 Elsevier Ltd. All rights reserved.