Transport of cholesterol into mitochondria is rate-limiting for bile acid synthesis via the alternative pathway in primary rat hepatocytes
Transport of cholesterol into mitochondria is rate-limiting for bile acid synthesis via the alternative pathway in primary rat hepatocytes
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DOI：
10.1074/jbc.m205244200
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发表时间：
2002-12-13
影响因子：
4.8
通讯作者：
Hylemon, P
中科院分区：
文献类型：
--
作者：
Pandak, WM;Ren, SL;Hylemon, P
胆汁酸的合成主要通过两条途径进行：由微粒体胆固醇启动的“经典”途径。固醇7 α-羟化酶（CYP 7A 1）和“替代”（酸性）途径，由固醇27-羟化酶（CYP 27）启动。CYP 27位于胆固醇含量非常低的线粒体内膜。我们假设胆固醇进入线粒体的转运可能是胆汁酸合成的限速途径。编码类固醇生成急性调节（星星）蛋白（一种已知的线粒体胆固醇转运蛋白）的基因的过表达导致胆汁酸合成增加5倍。星星蛋白的增加与胆汁酸合成的增加一致。CYP 27过表达增加胆汁酸合成，
Bile acid synthesis occurs mainly via two pathways: the "classic" pathway, initiated by microsomal choles. terol 7alpha-hydroxylase (CYP7A1), and an "alternative" (acidic) pathway, initiated by sterol 27-hydroxylase (CYP27). CYP27 is located in the inner mitochondrial membrane, where cholesterol content is very low. We hypothesized that cholesterol transport into mitochondria may be rate-limiting for bile acid synthesis via the "alternative" pathway. Overexpression of the gene encoding steroidogenic acute regulatory (StAR) protein, a known mitochondrial cholesterol transport protein, led to a 5-fold increase in bile acid synthesis. An increase in StAR protein coincided with an increase in bile acid synthesis. CYP27 overexpression increased bile acid synthesis by