A 25-hydroxylation pathway of cholic acid biosynthesis in man and rat.
A 25-hydroxylation pathway of cholic acid biosynthesis in man and rat.
复制标题
人和大鼠胆酸生物合成的 25-羟基化途径。
DOI：
10.1172/jci108366
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发表时间：
1976
期刊：
影响因子：
--
通讯作者：
E. Mosbach
中科院分区：
文献类型：
--
作者：
S. Shefer;F. Cheng;B. Dayal;S. Hauser;G. Tint;G. Salen;E. Mosbach
本文描述了人和大鼠体内胆酸合成的途径，该途径涉及 25-羟基化中间体，并由微粒体和可溶性酶催化。使用正常血脂受试者、脑腱黄瘤病患者和大鼠的肝脏部分研究了所涉及酶的亚细胞定位、立体特异性和其他特性。在 NADPH 和 O2 存在下，微粒体级分将 5β-胆甾烷-3α,7α,12α,25-四醇转化为 5β-胆甾烷-3α,7α,12α,24β,25-戊醇。还形成5β-胆甾烷-3α，7α，12α，24α，25-戊醇，5β-胆甾烷-3α，7α，12α，-23xi，25-戊醇和5β-胆甾烷-3α，7α，12α，25，26-戊醇。在 NAD 存在下，5β-胆甾烷-3α,7α,12α,24β,25-五醇（但不是形成的其他 5β-胆甾烷五醇）通过可溶性酶以良好的产率转化为胆酸。这些实验证明了胆酸合成中存在侧链降解途径，该途径不涉及C-26处的羟基化或线粒体的参与。
This paper describes a pathway of cholic acid synthesis, in man and in the rat, which involves 25-hydroxylated intermediates and is catalyzed by microsomal and soluble enzymes. The subcellular localization, stereospecificity, and other properties of the enzymes involved were studied with liver fractions of normolipidemic subjects, cerebrotendinous xanthomatosis patients, and rats. 5beta-Cholestane-3alpha,7alpha,12alpha,25-tetrol was converted to 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol by the microsomal fraction in the presence of NADPH and O2. 5beta-Cholestane-3alpha,7alpha,12alpha,24alpha,25-pentol, 5beta-cholestane-3alpha,7alpha,12alpha,-23xi,25-pentol, and 5beta-cholestane-3alpha,7alpha,12alpha,25,26-pentol were also formed. In the presence of NAD, 5beta-cholestane-3alpha,7alpha,12alpha,24beta,25-pentol, but not the other 5beta-cholestanepentols formed, was converted to cholic acid by soluble enzymes in good yield. These experiments demonstrate the existence of a pathway for side-chain degradation in cholic acid synthesis which does not involve hydroxylation at C-26 or the participation of mitochondria.