Increased formation of ursodeoxycholic acid in patients treated with chenodeoxycholic acid.
Increased formation of ursodeoxycholic acid in patients treated with chenodeoxycholic acid.
复制标题
使用鹅去氧胆酸治疗的患者中熊去氧胆酸的形成增加。
DOI：
10.1172/jci107596
复制
发表时间：
1974
期刊：
影响因子：
--
通讯作者：
Erwin H. Mosbach
中科院分区：
文献类型：
--
作者：
Gerald Salen;G. Tint;Bess Eliav;Norma Deering;Erwin H. Mosbach
对3例脑腱黄瘤病和4例胆结石患者的鹅去氧胆酸的7β-羟基同分异构体熊去氧胆酸的形成进行了研究。用鹅去氧胆酸0.75g/d治疗4个月后，用气-液色谱分析胆汁总酸组成。用质谱仪鉴定单个胆汁酸。治疗前，脑腱黄瘤病(CTX)患者胆汁中胆酸含量为85%，鹅去氧胆酸为7%，脱氧胆酸为3%，别胆酸为3%，类固醇为2%；胆结石患者胆汁中胆酸含量为45%，鹅去氧胆酸为43%，脱氧胆酸为11%，石胆酸为1%。在所有受试者中，4个月的鹅去氧胆酸治疗使胆汁酸的比例增加到约80%，胆酸占总胆汁酸的比例降低到3%，其余17%的胆汁酸被鉴定为熊去氧胆酸。静脉注射[~3H]鹅去氧胆酸后，胆汁熊去氧胆酸的比活力超过鹅去氧胆酸的比活力，其比活力衰减曲线符合前体-产物关系。给另一名用鹅去氧胆酸治疗的病人注射7-酮胆酸时，在熊去氧胆酸和鹅去氧胆酸部分都检测到放射性。这些结果表明，在接受鹅去氧胆酸治疗的患者中形成了大量的熊去氧胆酸。熊去氧胆酸可能是由鹅去氧胆酸通过7-酮胆酸合成的。
The formation of ursodeoxycholic acid, the 7 beta-hydroxy epimer of chenodeoxycholic acid, was investigated in three subjects with cerebrotendinous xanthomatosis and in four subjects with gallstones. Total biliary bile acid composition was analyzed by gas-liquid chromatography before and after 4 months of treatment with 0.75 g/day of chenodeoxycholic acid. Individual bile acids were identified by mass spectrometry. Before treatment, bile from cerebrotendinous xanthomatosis (CTX) subjects contained cholic acid, 85%; chenodeoxycholic acid, 7%; deoxycholic acid, 3%; allocholic acid, 3%; and unidentified steroids, 2%; while bile from gallstone subjects contained cholic acid, 45%; chenodeoxycholic acid, 43%; deoxycholic acid, 11%, and lithocholic acid, 1%. In all subjects, 4 months of chenodeoxycholic acid therapy increased the proportion of this bile acid to approximately 80% and decreased cholic acid to 3% of the total biliary bile acids, the remaining 17% of bile acids were identified as ursodeoxycholic acid. After the intravenous injection of [3H]chenodeoxycholic acid, the specific activity of biliary ursodeoxycholic acid exceeded the specific activity of chenodeoxycholic acid, and the resulting specific activity decay curves suggested precursor-product relationships. When [3H]7-ketolithocholic acid was administrated to another patient treated with chenodeoxycholic acid, radioactivity was detected in both the ursodeoxycholic acid and chenodeoxycholic acid fractions. These results indicate that substantial amounts of ursodeoxycholic acid are formed in patients treated with chenodeoxycholic acid. The ursodeoxycholic acid was synthesized from chenodeoxycholic acid presumably via 7-ketolithocholic acid.