Abstract
UDP-glucuronosyltransferases (UGT) isoforms catalyze the glucuronidation towards many lipophilic endogenous and exogenous chemicals to excrete from the body. Dietary compounds are also glucuronidated by UGT isoforms and its biological effects depend, in part, on formation of the glucuronides. To evaluate the contribution of each UGT for glucuronidation towards the dietary bioflavonoid, quercetin, we have constructed yeast expression system of human UGT1As and analyzed the glucuronidation using the recombinant UGTs. UGT1A1 catalyzed glucuronidation towards 3'- and 4'-hydroxyl moiety of quercetin with high catalytic efficiency and substrate inhibition kinetics. UGT1A9 produced 3'-, 4'-, 3- and 7-glucuronides. Extrahepatic human UGT1A7, 1A8 and 1A10, which were found throughout the gastrointestinal tract, showed the high glucuronidation efficiency towards 3'- and 4'-hydroxyl moiety. These results suggest that glucuronidation towards quercetin is catalyzed by several UGT isoforms, and recombinant human UGT expression system in yeast provides information on the regioselectivity of glucuronidation of dietary bioflavonoids.
