Journal of Lipid Research, Vol. 9, 328-333, May 1968
Copyright © 1968 by Lipid Research, Inc.

7-Hydroxylation of cholestanol by rat liver microsomes

Sarah Shefer , Susan Hauser , 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

In a study of the mechanism whereby 5-bile acids are formed from cholestanol, the 7-hydroxylation of cholestanol was investigated in rat liver preparations in vitro. It was found that in the presence of NADPH and oxygen, rat liver microsomes catalyzed the 7-hydroxylation of cholestanol to the same extent as that of cholesterol.

The rate of the hydroxylation was enhanced by prior treatment of the experimental rats with cholestyramine (a bile acid sequestrant) or by establishment of bile fistulas—i.e., by partial or complete removal of bile acids from the enterohepatic circulation. The 7-hydroxylation reaction was further stimulated by pretreatment of the animals with phenobarbital, a drug known to produce increased biosynthesis of hepatic endoplasmic membranes. The 7-hydroxylase was inhibited by the reaction product, by sterols with 7-keto or 7ßbeta;-hydroxyl groups, and also by mono- and dihydroxy bile acids of the 5ßbeta;-series, although cholic acid or taurocholate produced no inhibition unless added in high concentrations.

The results of these studies are in accord with the concept that the presence of a ⁵-double bond is not required for the enzymatic formation of the 7-hydroxy derivative. The rate of this hydroxylation reaction in vitro appears to depend on the concentration of bile salts in the enterohepatic circulation of the experimental animals from whom the microsomes were obtained.

Supplementary key words 7-hydroxylation • in vitro • rat liver microsomes • cholesterol • cholestanol • phenobarbital • cholestyramine • bile acids

Submitted on November 27, 1967
Accepted on January 12, 1968

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