Stereochemistry of intermediates in the conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid to cholic acid by rat liver peroxisomes.

We have investigated the stereochemistry of the side chain of the intermediates, 3 alpha, 7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic acid and 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestanoic acid, in the conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid to cholic acid by rat liver peroxisomes. The intermediates formed were converted to the p-bromophenacyl ester derivatives and analyzed by reversed-phase high-performance liquid chromatography. Only the (24E) form of the two isomers of the delta 24-unsaturated acid and the (24R,25S) form of the four isomers at C-24 and C-25 of the 24-hydroxy acid were found to be formed stereospecifically from either (25R)- or (25S)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid. Formation of the other isomers of the alpha beta-unsaturated bile acid or the beta-hydroxy bile acid was not detected. The findings support the proposed pathway for the side-chain cleavage in cholic acid biosynthesis, which is thought to be similar to that of peroxisomal fatty acid beta-oxidation.