Kirkpatrick R B, Falany C N, Tephly T R
J Biol Chem. 1984 May 25;259(10):6176-80.
The glucuronidation of bile acids is an important pathway for the detoxification and elimination of retained bile acids during cholestasis. A 3-OH-specific androgen UDP-glucuronyltransferase was purified from solubilized female rat liver microsomes using Chromatofocusing and UDP- hexanolamine -Sepharose 4B affinity chromatography. The purified 3-OH androgen UDP-glucuronyltransferase is reactive towards bile acids, including lithocholic acid, deoxycholic acid, and ursodeoxycholic acid, in addition to the androgenic steroids etiocholanolone and androsterone. The highest activity towards bile acids is seen with lithocholic acid-24-methyl ester, and no activity is seen with lithocholic acid-3 alpha-sulfate or 5 beta- cholanic acid-3-one. No glucuronidation activity towards bile acids was observed with either a purified 17-OH steroid UDP-glucuronyltransferase or a p-nitrophenol-UDP-glucuronyltransferase. Lithocholic acid competitively inhibits etiocholanolone glucuronidation by the purified 3-OH androgen isoenzyme. These results suggest that a UDP-glucuronyltransferase isoenzyme is present in female rat liver which is capable of specifically glucuronidating the 3-OH group of bile acids and androgenic steroids.
胆汁酸的葡萄糖醛酸化是胆汁淤积期间滞留胆汁酸解毒和消除的重要途径。使用层析聚焦法和UDP-己醇胺-Sepharose 4B亲和层析法从溶解的雌性大鼠肝微粒体中纯化出一种3-OH特异性雄激素UDP-葡萄糖醛酸基转移酶。纯化的3-OH雄激素UDP-葡萄糖醛酸基转移酶除了对雄激素类固醇本胆烷醇酮和雄酮有反应外，还对包括石胆酸、脱氧胆酸和熊去氧胆酸在内的胆汁酸有反应。对胆汁酸活性最高的是石胆酸-24-甲酯，而石胆酸-3α-硫酸盐或5β-胆烷酸-3-酮则无活性。纯化的17-OH类固醇UDP-葡萄糖醛酸基转移酶或对硝基苯酚-UDP-葡萄糖醛酸基转移酶均未观察到对胆汁酸的葡萄糖醛酸化活性。石胆酸竞争性抑制纯化的3-OH雄激素同工酶对本胆烷醇酮的葡萄糖醛酸化。这些结果表明，雌性大鼠肝脏中存在一种UDP-葡萄糖醛酸基转移酶同工酶，它能够特异性地将胆汁酸和雄激素类固醇的3-OH基团葡萄糖醛酸化。
