Human UDP-glucuronosyltransferase isoforms involved in bisphenol A glucuronidation

Chemosphere. 2008 Dec;74(1):33-6. doi: 10.1016/j.chemosphere.2008.09.053. Epub 2008 Nov 5.

Abstract

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 microM) and high- (20 microM) 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 microM and 4250 pmol min(-1)mg(-1)protein for pooled human liver microsomes, and 8.68 microM 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Benzhydryl Compounds
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Female
  • Glucuronides / chemistry
  • Glucuronides / metabolism*
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kinetics
  • Male
  • Microsomes, Liver / metabolism
  • Middle Aged
  • Phenols / chemistry
  • Phenols / metabolism*
  • Recombinant Proteins / metabolism
  • Young Adult

Substances

  • Benzhydryl Compounds
  • Glucuronides
  • Isoenzymes
  • Phenols
  • Recombinant Proteins
  • Glucuronosyltransferase
  • bisphenol A