Peroxisomal oxidation of the steroid side chain in bile acid formation

An overview of the formation of the primary bile acids is given with special emphasis on the final steps, ie the oxidative cleavage of the steroid side chain. The enzymes involved in this oxidation are localized to liver peroxisomes and catalyze conversion of di- and trihydroxy-5 beta-cholestanoic acid into chenodeoxycholic and cholic acid, respectively. Two of the intermediates in cholic acid formation have been identified, viz 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. The corresponding hypothetical 24-oxo compound has not been finally identified. The first enzyme in the reaction sequence, trihydroxy-5 beta-cholestanoyl-CoA oxidase, has recently been partly purified and shown to be separate from the corresponding peroxisomal acyl-CoA oxidase. The subsequent enzymes, the trifunctional enzyme and the thiolase, are most certainly shared in the oxidation of both fatty acids and cholestanoic acids. In several peroxisomal disorders bile acid intermediates with an uncleaved steroid side chain accumulate, thus clearly demonstrating the importance of liver peroxisomes in the normal formation of bile acids in man.