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

Abstract

This study tries to find structure-metabolism relationships between flavonoids and human UGT1A3 and UGT1A9. The glucuronidation of flavonoids was studied with recombinant UGT1A3 and UGT1A9, and the glucuronidation activity was determined by HPLC. 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. From the quantitative study, UGT1A9 in general has higher glucuronidation efficiency than UGT1A3.