Identifying and applying a highly selective probe to simultaneously determine the O-glucuronidation activity of human UGT1A3 and UGT1A4

Sci Rep. 2015 Apr 17:5:9627. doi: 10.1038/srep09627.

Abstract

Glucuronidation mediated by uridine 5'-diphospho (UDP)-glucuronosyltransferase is an important detoxification pathway. However, identifying a selective probe of UDP- glucuronosyltransferase is complicated because of the significant overlapping substrate specificity displayed by the enzyme. In this paper, desacetylcinobufagin (DACB) 3-O- and 16-O-glucuronidation were found to be isoform-specific probe reactions for UGT1A4 and UGT1A3, respectively. DACB was well characterized as a probe for simultaneously determining the catalytic activities of O-glucuronidation mediated by UGT1A3 and UGT1A4 from various enzyme sources, through a sensitive analysis method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bufanolides / chemistry*
  • Bufanolides / metabolism
  • Enzyme Inhibitors / chemistry
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Kinetics
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Substrate Specificity

Substances

  • Bufanolides
  • Enzyme Inhibitors
  • Protein Isoforms
  • Recombinant Proteins
  • bilirubin glucuronoside glucuronosyltransferase
  • desacetylcinobufagin
  • UDP-glucuronosyltransferase, UGT1A3
  • Glucuronosyltransferase