Structure-metabolism relationships for the glucuronidation of flavonoids by UGT1A3 and UGT1A9

J Pharm Pharmacol. 2011 Feb;63(2):297-304. doi: 10.1111/j.2042-7158.2010.01168.x. Epub 2010 Nov 18.

Abstract

Objectives: This study tries to find structure-metabolism relationships between flavonoids and human UGT1A3 and UGT1A9.

Methods: The glucuronidation of flavonoids was studied with recombinant UGT1A3 and UGT1A9, and the glucuronidation activity was determined by HPLC.

Key findings: Of the flavonoids studied, it was shown for the first time that baicalein, quercetin-3-OCH(2) OCH(3) , quercetin-4'-CH(3) , quercetin-3'-OCH(3) and quercetin-3'-Br are substrates of UGT1A3. Wogonin, baicalein, quercetin-4'-Cl, quercetin-3-OCH(2) OCH(3) , quercetin-3-O-arabinoside, quercetin-4'-CH(3) , quercetin-3'-OCH(3) and quercetin-3'-Br are the newly reported substrates of UGT1A9. The preferred substrates for UGT1A3 and UGT1A9 contain the hydroxyl group at the C7-position. The glycon and the position of the B ring have conspicuous influences on the glucuronidation activity, and other chemical structures of flavonoids have minor effects.

Conclusions: From the quantitative study, UGT1A9 in general has higher glucuronidation efficiency than UGT1A3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chromatography, High Pressure Liquid / methods
  • Flavonoids / chemistry*
  • Flavonoids / metabolism*
  • Glucuronides / chemistry
  • Glucuronides / metabolism
  • Glucuronosyltransferase / chemistry*
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Kinetics
  • Structure-Activity Relationship
  • UDP-Glucuronosyltransferase 1A9

Substances

  • Flavonoids
  • Glucuronides
  • UGT1A9 protein, human
  • UDP-glucuronosyltransferase, UGT1A3
  • Glucuronosyltransferase
  • UDP-Glucuronosyltransferase 1A9