Factors Influencing Cholesterol 7α-Hydroxylase Activity in the Rat Liver

Abstract

From a quantitative standpoint the breakdown of cholesterol to bile acids is very important and from the studies of Lindstedt (1) it was argued that one of the possible early metabolites on this pathway was cholest-5-en-3β, 7α-diol (7α-hydroxycholesterol). As far as can be established bile acid formation occurs exclusively in the liver and the enzymic hydroxylation of cholesterol to 7α-hydroxy-cholesterol is a function of the endoplasmic reticulum or the microsomal fraction of rat liver. Since few sterol metabolites other than bile acids have oxygenated functions at C₇ it follows that if 7α-hydroxylation is the initial step on the pathway of degradation of cholesterol to bile acids, then this proposed reaction might be the rate limiting reaction. Thus the introduction of the 7α-hydroxyl group into the ubiquitous cholesterol molecule would result in the conversion of cholesterol to 7α-hydroxycholesterol, a metabolite on an exclusive pathway to bile acids. Such branchpoints in metabolism are possible targets for regulation mechanisms. The conversion of cholesterol to bile acids has been reviewed by Danielsson (2).