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

摘要

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.