Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7

Abstract

Previous studies have shown that several endogenous compounds, such as bilirubin and certain bile acids, are glucosidated in human liver. In this work, we have identified human UDP-glucuronosyltransferase 2B7 (UGT2B7) as the isoform that catalyzes the glucosidation of hyodeoxycholic acid (HDCA). The glucosidation by UGT2B7 was specific for HDCA and was not observed with the other bile acids examined, lithocholic acid, chenodeoxycholic acid, and ursodeoxycholic acid. The kinetics of HDCA glucuronidation and glucosidation by UGT2B7 were characterized. The K m values for glucuronidation and glucosidation of HDCA were 11.6 and 17.9 μM, respectively, with V max values of 4.15 nmol/min/mg protein for glucuronidation and 3.28 nmol/min/mg for glucosidation. At a fixed concentration of HDCA, the apparent K m for UDP-glucuronic acid was 89 μM with a V max of 3.53 nmol/min/mg. The corresponding parameters for UDP-glucose were 442 μM and 1.98 nmol/min/mg, respectively. UGT2B7 catalyzed the addition of the glucose and glucuronic acid moieties to an hydroxyl group on HDCA and also possessed some capacity to use UDP-xylose as sugar donor. The two polymorphic variants of UGT2B7, UGT2B7 ∗1 and UGT2B7 ∗2 could both glucosidate HDCA. This is the first report that identifies UGT2B7 as the enzyme responsible for the glucosidation of the bile acid, HDCA.