ABSTRACT

The rate of overall bile acid biosynthesis is regulated by bile acids at the rate-limiting enzyme of the neutral pathway, cholesterol 7α-hydroxylase. Bile acid feedback also regulates other regulatory enzymes in the pathway, oxysterol 7α-hydroxylase, sterol 12αhydroxylase, and 3β-HSD. It has been well established that the rate of bile acid synthesis and cholesterol 7α-hydroxylase activity is regulated by the hydrophobicity index of bile. Hydrophobic bile acids are more potent inhibitors of bile acid biosynthesis than hydrophilic bile acids (Heuman et al., 1989). Sterol 12α-hydroxylase may regulate hydrophobicity of bile by regulating the ratio of cholic acid to chenodeoxycholic acid.