Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7.
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 microM, 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 microM with a V(max) of 3.53 nmol/min/mg. The corresponding parameters for UDP-glucose were 442 microM 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.
Mackenzie
Peter
P
Department of Clinical Pharmacology, Flinders University and Flinders Medical Center, Bedford Park, SA 5042, Australia. peter.mackenzie@flinders.edu.au
Little
Joanna M
JM
Radominska-Pandya
Anna
A
D002478:Cells, Cultured; D003840:Deoxycholic Acid / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D007527:Isoenzymes; D011994:Recombinant Proteins; D003840:Deoxycholic Acid; C010471:hyodeoxycholic acid; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase