Biosynthesis of bile acids in man. Hydroxylation of the C27-steroid side chain.
Open Access
- 1 March 1975
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 55 (3), 478-486
- https://doi.org/10.1172/jci107954
Abstract
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.Keywords
This publication has 18 references indexed in Scilit:
- A Biochemical Abnormality in Cerebrotendinous Xanthomatosis IMPAIRMENT OF BILE ACID BIOSYNTHESIS ASSOCIATED WITH INCOMPLETE DEGRADATION OF THE CHOLESTEROL SIDE CHAINJCI Insight, 1974
- Enzymatic Characteristics of CO‐Sensitive 26‐Hydroxylase System for 5β‐Cholestane‐3α, 7α, 12α‐triol in Rat‐Liver Mitochondria and Its Intramitochondrial LocalizationEuropean Journal of Biochemistry, 1973
- The formation and metabolism of 3α,7α-dihydroxy-5β-cholestan-26-oic acid in manJCI Insight, 1971
- Oxidation of 5β‐Cholestane‐3α, 7α, 12α‐triol by Rat Liver MicrosomesEuropean Journal of Biochemistry, 1970
- On the Conversion of Cholesterol to 5beta-Cholestane-3alpha, 7alpha-Diol in Guinea Pig Liver HomogenatesEuropean Journal of Biochemistry, 1967
- Conversion of Cholesterol to Trihydroxycoprostanic Acid and Cholic Acid in Man*JCI Insight, 1964
- CHOLIC-ACID TURNOVER + BILIARY BILE-ACID COMPOSITION IN HUMANS WITH ABNORMAL THYROID FUNCTION - BILE ACIDS + STEROIDS 1391964
- Thin-layer chromatography of bile acidsJournal of Lipid Research, 1963
- Formation of trihydroxycoprostanic acid from cholesterol in manBiochimica et Biophysica Acta, 1962
- CATABOLISM IN VITRO OF CHOLESTEROL .2. FURTHER STUDIES ON OXIDATION OF CHOLESTEROL BY RAT LIVER MITOCHONDRIA1961