Journal of Lipid Research, Vol. 11, 404-411, September 1970
Copyright © 1970 by Lipid Research, Inc.

Biochemical site of regulation of bile acid biosynthesis in the rat

Sarah Shefer , Susan Hauser , Ihor Bekersky , and Erwin H. Mosbach

Department of Laboratory Diagnosis, Public Health Research Institute of the City of New York, Inc., and the Bureau of Laboratories, New York City Department of Health, New York 10016

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 7-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 7-hydroxylase provided that hepatic cholesterol synthesis is adequate.

Supplementary key words in vivo bile acid biosynthesis • enterohepatic circulation • cholesterol 7-hydroxylase

Submitted on February 16, 1970
Accepted on April 30, 1970

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