Abstract

A full-length cDNA clone (HE8a) for a human hepatic UDP-glucuronosyltransferase was isolated from a human liver cDNA library and stably expressed in human embryonic kidney 293 (HK293) cells. Sequence analysis of the cDNA revealed that it was identical to UDPGTh-3 isolated by Chen et al. (Biochemistry 32, 10648-10657, 1993). HE8a is a member of the UGT2B gene family, and it has been designated UGT2B15. Over 100 compounds were tested for their reactivity with the expressed protein. UGT2B15 stably expressed in HK293 cells displayed glucuronidation activity toward several classes of xenobiotic substrates, including simple phenolic compounds, 7-hydroxylated coumarins, flavonoids, anthraquinones, and certain drugs and their hydroxylated metabolites. In addition, the expressed enzyme also catalyzed the glucuronidation of endogenous estrogens and androgens. Apparent KM and enzyme efficiency values for certain food-derived substrates (e.g., naringenin and eugenol) for expressed UGT2B15 were similar to those determined for endobiotic substrates, suggesting that some naturally occurring substances are good substrates for this enzyme and that glucuronidation of endogenous compounds could be affected by xenobiotics derived from dietary sources.