Radominska A, Green M D, Zimniak P, Lester R, Tephly T R
Department of Internal Medicine, University of Texas Medical School, Houston 77225.
J Lipid Res. 1988 Apr;29(4):501-8.
Microsomal preparations from livers of Sprague-Dawley rats catalyze the glucuronidation of 3 alpha-hydroxy-5 beta-H (3 alpha, 5 beta) short-chain bile acids (C20-C23), predominantly at the hydroxyl group, while the glucuronidation of 3 beta, 5 beta short-chain bile acids occurs exclusively at the carboxyl group. A similar pattern of conjugation was also observed in Wistar rats having normal levels of 3-hydroxysteroid UDP-glucuronosyltransferase. Significant reductions of formation rates for hydroxyl-linked, but not carboxyl-linked, short-chain bile acid glucuronides were observed in hepatic microsomes from Wistar rats with low 3-hydroxysteroid UDP-glucuronosyltransferase activity. 3-Hydroxysteroid UDP-glucuronosyltransferase, purified to homogeneity from Sprague-Dawley liver microsomes, catalyzed the 3-O-glucuronidation of 3 alpha, 5 beta C20-23 bile acids, as well as of lithocholic and isolithocholic acids (C24). The apparent Michaelis constants (KM) for short-chain bile acids were similar to the value obtained for androsterone. 3 alpha, 5 beta-C20 and 3 beta, 5 beta-C20 competitively inhibited glucuronidation of androsterone by the purified 3-hydroxysteroid UDP-glucuronosyltransferase. Purified 17 beta-hydroxysteroid and p-nitrophenol UDP-glucuronosyltransferases did not catalyze the glucuronidation of bile acids. In addition, none of the purified transferases catalyzed the formation of carboxyl-linked bile acid glucuronides. The results show that 3-hydroxysteroid UDP-glucuronosyltransferase, an enzyme specific for 3-hydroxyl groups of androgenic steroids and some conventional bile acids, also catalyzes the glucuronidation of 3 alpha-hydroxyl (but not carboxyl) groups of 3 alpha, 5 beta short-chain bile acids.
来自斯普拉格 - 道利大鼠肝脏的微粒体制剂催化3α - 羟基 - 5β - H（3α，5β）短链胆汁酸（C20 - C23）的葡萄糖醛酸化，主要发生在羟基上，而3β，5β短链胆汁酸的葡萄糖醛酸化仅发生在羧基上。在具有正常水平的3 - 羟基类固醇UDP - 葡萄糖醛酸基转移酶的Wistar大鼠中也观察到了类似的结合模式。在3 - 羟基类固醇UDP - 葡萄糖醛酸基转移酶活性低的Wistar大鼠的肝微粒体中，观察到羟基连接的短链胆汁酸葡萄糖醛酸苷的形成速率显著降低，但羧基连接的则没有。从斯普拉格 - 道利大鼠肝脏微粒体中纯化至同质的3 - 羟基类固醇UDP - 葡萄糖醛酸基转移酶催化3α，5β C20 - 23胆汁酸以及石胆酸和异石胆酸（C24）的3 - O - 葡萄糖醛酸化。短链胆汁酸的表观米氏常数（KM）与雄甾酮获得的值相似。3α，5β - C20和3β，5β - C20竞争性抑制纯化的3 - 羟基类固醇UDP - 葡萄糖醛酸基转移酶对雄甾酮的葡萄糖醛酸化。纯化的17β - 羟基类固醇和对硝基苯酚UDP - 葡萄糖醛酸基转移酶不催化胆汁酸的葡萄糖醛酸化。此外，没有一种纯化的转移酶催化羧基连接的胆汁酸葡萄糖醛酸苷的形成。结果表明，3 - 羟基类固醇UDP - 葡萄糖醛酸基转移酶是一种对雄激素类固醇和一些传统胆汁酸的3 - 羟基具有特异性的酶，它也催化3α，5β短链胆汁酸的3α - 羟基（而非羧基）的葡萄糖醛酸化。
