Bile acid induced interconversion of 3-hydroxy-3-methylglutaryl Coenzyme A reductase in cultured intestine.

The effect of bile acids and bile acid/cholesterol micelles on 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key enzyme of cholesterol synthesis, was investigated in cultured intestine. Glycocholic and glycodeoxycholic acid both suppressed total (fully activated) reductase activity after 3 h culture. The portion of expressed reductase, determined in the presence of NaF, was unaffected at 3 h, but decreased after 24 h of bile acid treatment. In contrast, total enzyme activity was stimulated up to 2.5-fold at 24 h; this bile acid effect was blocked by additional cholesterol. These results suggest that bile acids modulate both total reductase activity and the activation state of the enzyme in cultured intestine.