Identification of human UDP-glucuronosyltransferase isoform(s) responsible for the C-glucuronidation of phenylbutazone

Arch Biochem Biophys. 2006 Oct 1;454(1):72-9. doi: 10.1016/ Epub 2006 Aug 7.


Glucuronidation is a major metabolic pathway in the biotransformation of many xenobiotics and endogeneous compounds. There have been many studies on the formation of O-, N- or S-glucuronides and identification of the UDP-glucuronosyltransferase (UGT) isoforms responsible for the formation of these glucuronides. However, there is no information available on which UGT isoform(s) catalyzes C-glucuronidation. In the present study, 16 human UGTs (UGTs 1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B11, 2B15, 2B17 and 2B28) were cloned and expressed in baculovirus-infected insect cells and investigated to determine their C-glucuronidating activity toward phenylbutazone (PB). Among the UGT isoforms investigated, only UGT1A9 catalyzed PB C-glucuronidation. Human liver and kidney microsomes, which are well known to express UGT1A9, had C-glucuronidating activity toward PB. However, the jejunum, which did not express UGT1A9, had no C-glucuronidating activity. These results demonstrate for the first time that PB C-glucuronidation is catalyzed by only UGT1A9.

MeSH terms

  • Cells, Cultured
  • Glucuronides / metabolism*
  • Glucuronosyltransferase / analysis
  • Glucuronosyltransferase / chemistry
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Isoenzymes / metabolism
  • Jejunum / metabolism*
  • Kidney / metabolism*
  • Liver / metabolism*
  • Microsomes, Liver / metabolism*
  • Phenylbutazone / metabolism*


  • Glucuronides
  • Isoenzymes
  • Glucuronosyltransferase
  • Phenylbutazone