Interaction of bisphenol A with human UDP-glucuronosyltransferase 1A6 enzyme

Environmental Toxicology
Nobumitsu HaniokaShizuo Narimatsu

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.

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Citations

Sep 6, 2013·Proceedings. Biological Sciences·Sandrine G ClairardinRachel M Bowden
Dec 8, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Janis L CoughlinBrian Buckley
Nov 29, 2013·Journal of Epidemiology and Community Health·Mee-Ri LeeYun-Chul Hong
Dec 30, 2015·Marine Environmental Research·Miriam PérezGuillermo Blustein
Nov 8, 2008·Chemosphere·Nobumitsu HaniokaShizuo Narimatsu
Jul 15, 2015·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Nataša MilićMilica Medić-Stojanoska
Apr 23, 2020·International Journal of Environmental Research and Public Health·Jin Hee Kim, Yun-Chul Hong
Feb 17, 2017·Environmental Health : a Global Access Science Source·Jin Hee Kim, Yun-Chul Hong
Aug 22, 2014·Chemical Research in Toxicology·Nicolas QuesnotMarie-Anne Robin

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