24-羟基胆甾醇介导胆汁酸和胆汁盐的合成
中文名称
通路描述
在体内，24-羟基胆甾醇在脑中合成，转运至肝脏，并在此处转化为胆汁酸和胆汁盐。该途径是胆汁酸和胆汁盐的次要来源，但对从大脑排出过量胆固醇至关重要（Bjorkhem et al. 1998; Javitt 2002）。在肝脏中，24-羟基胆甾醇转化为胆汁酸和胆汁盐的起始步骤是羟基化和氧化还原反应，形成4-胆甾烯-7α,24(S)-二醇-3-酮。随后途径分支：4-胆甾烯-7α,24(S)-二醇-3-酮的羟基化生成4-胆甾烯-7α,12α,24(S)-三醇-3-酮，最终形成胆酸；而其还原生成5β-胆甾烷-7α,24(S)-二醇-3-酮则形成去氧胆酸。在两条分支中，细胞质、线粒体基质和过氧化物酶体基质的反应导致环结构修饰、侧链缩短和氧化、转化为辅酶A衍生物，以及与甘氨酸或牛磺酸结合（Russell 2003）。这些反应如图示。最后三个反应与由7α-羟基化启动的胆汁盐合成反应相同，并以无底物的箭头表示。
英文描述
Synthesis of bile acids and bile salts via 24-hydroxycholesterol In the body, 24-hydroxycholesterol is synthesized in the brain, exported to the liver, and converted there to bile acids and bile salts. This pathway is only a minor source of bile acids and bile salts, but appears to be critical for the disposal of excess cholesterol from the brain (Bjorkhem et al. 1998; Javitt 2002).In the liver, conversion of 24-hydroxycholesterol to bile acids and bile salts is initiated with hydroxylation and oxidoreductase reactions to form 4-cholesten-7alpha,24(S)-diol-3-one. The pathway then branches: hydroxylation of 4-cholesten-7alpha,24(S)-diol-3-one to 4-cholesten-7alpha,12alpha,24(S)-triol-3-one leads ultimately to the formation of cholate, while its reduction to 5beta-cholestan-7alpha,24(S)-diol-3-one leads to chenodeoxycholate formation. In both branches, reactions in the cytosol, the mitochondrial matrix, and the peroxisomal matrix result in modifications to the ring structure, shortening and oxidation of the side chain, conversion to a Coenzyme A derivative, and conjugation with the amino acids glycine or taurine (Russell 2003). These reactions are outlined in the figure below. The final three reactions are identical to ones of bile salt synthesis initiated by 7alpha-hydroxylation and are shown as arrows with no substrates.
所含基因
13 个基因