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Interaction of bisphenol a with human UDP‐glucuronosyltransferase 1A6 enzyme
Author(s) -
Hanioka Nobumitsu,
Takeda Yuri,
TanakaKagawa Toshiko,
Hayashi Keiko,
Jinno Hideto,
Narimatsu Shizuo
Publication year - 2008
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.20345
Subject(s) - glucuronidation , microsome , chemistry , enzyme , bisphenol a , yeast , glucuronosyltransferase , biochemistry , microsoma , organic chemistry , epoxy
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 μM for liver microsomes, and 84.6 and 80.3 μM 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 μM, respectively. In yeast cell microsomes expressing humUGT1A6, 5‐HT glucuronidation activities were noncompetitively inhibited by BPA ( K i value, 65.5 μM), whereas the inhibition of 4‐MU glucuronidation activities by BPA exhibited the mixed type ( K i value, 42.5 μM). 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. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.