Formation of bile acids in man: conversion of cholesterol into 5β-cholestane-3α,7α,12α-triol in liver homogenates

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Abstract

The mechanisms of the conversion of cholesterol into bile acids in man were studied by examining the metabolism of cholesterol-1,2-3H, cholest-5-ene-3β,7α-diol-7β-3H, tritiumlabeled 7α-hydroxycholest-4-en-3-one, 7α,12α-dihydroxycholest-4-en-3-one, and cholest-5-ene-3β,7α,12α-triol in fractions of liver homogenates. The 20,000 g supernatant fluid catalyzed the conversion of cholesterol into cholest-5-ene-3β,7α-diol, 7α-hydroxycholest-4-en-3-one, 7α-12α-dihydroxycholest-4-en-3-one, and 5β-cholestane-3α,7α,12α-triol. In the presence of microsomal fraction fortified with NAD+, cholest-5-ene-3β,7α-diol was converted into 7α-hydroxycholest-4-en-3-one, and when this fraction was fortified with NADPH small amounts of cholest-5-ene-3β-7α,12α-triol were formed. 7α-Hydroxycholest-4-en-3-one was metabolized into 7α-12α-dihydroxycholest-4-en-3-one in the presence of microsomal fraction fortified with NADPH and into 5β-cholestane-3α,7α-diol in the presence of 100,000 g supernatant fluid. Cholest-5-ene-3β,7α,12α-triol was converted into 7α,12α-dihydroxycholest-4-en-3-one in the presence of microsomal fraction fortified with NAD+. The 100,000 g supernatant fluid catalyzed the conversion of 7α,12α-dihydroxycholest-4-en-3-one into 5β-cholestane-3α,7α,12α-triol. The sequence of reactions in the conversion of cholesterol into 5β-cholestane-3α,7α-diol and 5β-cholestane-3α,7α,12α-triol, the subcellular localization of the enzymes, and the cofactor requirements were found to be the same as those described for rat liver.

Authors

Ingemar Björkhem, Henry Danielsson, Kurt Einarsson, Gunnar Johansson