Björkhem I, Gustafsson J, Johansson G, Persson B
J Clin Invest. 1975 Mar;55(3):478-86. doi: 10.1172/JCI107954.
The first step in the degradation of the steroid side chain during biosynthesis of bile acids from cholesterol in man was studied in microsomal and mitochondrial fraction of homogenate of livers from 14 patients. The microsomal fraction was found to catalyze an efficient 25-hydroxylation of 5,8-cholestane-3a,7a,12atriol. A small extent of 23-, 24-, and 26-hydroxylation of the same substrate was observed. 53-Cholestane-3a,7adiol was hydroxylated in the 25-position only to a very small extent. The mitochondrial fraction was found to catalyze 26-hydroxylation of cholesterol, 5-cholestene-3P,7a-diol, 5P-cholestane-3a,7a-diol, 7a-hydroxy-4-cholesten-3-one, and 5,0-cholestane-3a,7a,12a-triol. Addition of Mg++ stimulated the 26-hydroxylation of cholesterol but had no effect or an inhibitory effect on 26-hydroxylation of the other substrates, indicating a heterogeneity of the mitochondrial 26-hydroxylating system. The level of 26-hydroxylase activity towards different substrates varied considerably with different mitochondrial preparations. The roles of the microsomal and mitochondrial 26- hydroxylations as well as the microsomal 25-hydroxylation in biosynthesis of bile acids in man are discussed. The results indicate that microsomal 26-hydroxylation is less important than mitochondrial 26-hydroxylation under normal conditions. The possibility that microsomal 25-hydroxylation is important cannot be ruled out.
对14例患者肝脏匀浆的微粒体和线粒体部分进行研究，以探讨人体从胆固醇生物合成胆汁酸过程中甾体侧链降解的第一步。发现微粒体部分能有效地催化5,8 - 胆甾烷 - 3α,7α,12α - 三醇的25 - 羟化反应。观察到同一底物有少量的23 -、24 - 和26 - 羟化反应。5β - 胆甾烷 - 3α,7α - 二醇仅在25位有极少量的羟化反应。发现线粒体部分能催化胆固醇、5 - 胆甾烯 - 3β,7α - 二醇、5β - 胆甾烷 - 3α,7α - 二醇、7α - 羟基 - 4 - 胆甾烯 - 3 - 酮和5β - 胆甾烷 - 3α,7α,12α - 三醇的26 - 羟化反应。添加Mg++能刺激胆固醇的26 - 羟化反应，但对其他底物的26 - 羟化反应无影响或有抑制作用，这表明线粒体26 - 羟化系统具有异质性。不同线粒体制剂对不同底物的26 - 羟化酶活性水平差异很大。文中讨论了微粒体和线粒体26 - 羟化反应以及微粒体25 - 羟化反应在人体胆汁酸生物合成中的作用。结果表明，在正常情况下，微粒体26 - 羟化反应不如线粒体26 - 羟化反应重要。不能排除微粒体25 - 羟化反应重要的可能性。
