Structural specificity of bile acid for inhibition of sterol synthesis in cell-free extracts of yeast

Abstract

Inhibitory effects of about 40 species of bile acids and related compounds or 14C incorporation from [14C]acetate into the nonsaponifiable fraction were examined with cell-free extracts of yeast. The presence of a 3α- or 7α-hydroxyl group and of a carboxyl group at the terminal of the side chain was required for the inhibitor yactivity. Introduction of an additional hydroxyl group in the 6α- or 12α-position abolished the inhibition. Bile acids with a 3β-hydroxyl group showed scarcely any inhibition. With regard to length of the side chain, the presence of a C4- or C5-side chain at the 17α-position was necessary. Conjugation with taurine scarcely affected the inhibition while conjugation with glycine lowered the inhibition to about one half. These specific structural requirements of bile acids for the inhibition indicate that the inhibition by bile acids is not a non-specific action due to their detergent action.Evidence was also presented suggesting that the site of inhibition by bile acids in the conversion of acetate into sterol was the reduction step of 3-hydroxy-3-methylglutaryl-CoA to mevalonate.