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 5β cholestane 3α,7α,12α triol. A small extent of 23, 24, and 26 hydroxylation of the same substrate was observed. 5β Cholestane 3α,7α diol 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 3β,7α diol, 5β cholestane 3α,7α diol, 7α hydroxy 4 cholesten 3 one, and 5β cholestane 3α,7α,12α 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.
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