Biochemical site of regulation of bile acid biosynthesis in the rat

Abstract

The production of bile salts by rat liver is regulated by a feedback mechanism, but it is not known which enzyme controls endogenous bile acid synthesis. In order to demonstrate the biochemical site of this control mechanism, bile fistula rats were infused intravenously with 14C-labeled bile acid precursors, and bile acid biosynthesis was inhibited as required by intraduodenal infusion of sodium taurocholate.The infusion of taurocholate (11–14 mg/100 g of rat per hr) inhibited the incorporation of acetate-1-14C, mevalonolactone-2-14C, and cholesterol-4-14C into bile acids by approximately 90%. In contrast, the incorporation of 7α-hydroxycholesterol-4-14C into bile acids was reduced by less than 10% during taurocholate infusion.These results indicate that the regulation of bile acid biosynthesis is exerted via cholesterol 7α-hydroxylase provided that hepatic cholesterol synthesis is adequate.

Keywords

• in vivo bile acid biosynthesis
• enterohepatic circulation
• cholesterol 7α-hydroxylase