Effect of Cholestyramine and Diet on Hydroxylations in the Biosynthesis and Metabolism of Bile Acids

Abstract

The effects of biliary drainage, cholestyramine treatment, starvation and a semisynthetic diet on nine different hydroxylations in the biosynthesis and metabolism of bile acids were studied. Biliary drainage and feeding a diet containing 3% cholestyramine resulted in a five‐ to seven‐fold stimulation of the 7α‐hydroxylation of cholesterol. Biliary drainage resulted in a five‐fold stimulation of the 12α‐hydroxylation of 7α‐hydroxy‐4‐cholesten‐3‐one. The other hydroxylations as well as the formation of 7α‐hydroxy‐4‐cholesten‐3‐one from 5‐cholestene‐3β,7α‐diol were unaffected by biliary drainage and cholestyramine treatment. Starvation stimulated the 12α‐hydroxylation of 7α‐hydroxy‐4‐cholesten‐3‐one about four‐fold. Feeding a fat‐free, semisynthetic diet resulted in a decrease in the rate of all reactions. The results support the concept that the 7α‐hydroxylation of cholesterol is a major rate‐limiting reaction in the biosynthesis of bile acids and indicate that also the 12α‐hydroxylation of 7α‐hydroxy‐4‐cholesten‐3‐one may be rate limiting to some extent.