On the Conversion of Cholesterol to 5beta-Cholestane-3alpha, 7alpha-Diol in Guinea Pig Liver Homogenates

作者：Ingemar Björkhem, Henry Danielsson, Kurt Einarsson · 发表于：European Journal of Biochemistry · 年份：1967 · DOI：10.1111/j.1432-1033.1967.tb00138.x · 被引用次数：34 · 研究领域：Drug Transport and Resistance Mechanisms、Cholesterol and Lipid Metabolism、Estrogen and related hormone effects

[1,2-3H2]Cholesterol was incubated with the 20,000 ×g supernatant fluid of homogenates of liver from guinea pigs that had chenodeoxycholic acid as the main primary bile acid. 7α-Hydroxycholest-4-en-3-one was identified as the main metabolite and cholest-5-ene-3β,7α-diol as a minor metabolite of cholesterol. [7β-3H]Cholest-5-ene-3β,7α-diol was transformed into 7α-hydroxycholest-4-en-3-one in the presence of microsomal fraction fortified with NAD. In the presence of 100,000 ×g supernatant fluid tritium-labeled 7α-hydroxycholest-4-en-3-one was converted into 5β-cholestane-3α,7α-diol by means of the intermediate formation of 7α-hydroxy-5β-cholestan-3-one. In the presence of 20,000 ×g supernatant fluid 7α-hydroxycholest-4-en-3-one was converted only to a small extent into 5β-cholestane-3α,7α-diol. In these incubations the formation of small amounts of cholest-4-ene-3β,7α-diol and cholest-4-ene-3α,7α-diol was demonstrated. The low extent of conversion of 7α-hydroxycholest-4-en-3-one into 5β-cholestane-3α,7α-diol in the presence of 20,000 ×g supernatant fluid might be due to an inhibition of the soluble Δ4-3-ketosteroid 5β-reductase by the microsomal fraction, as tritium-labeled 7α-hydroxy-5β-cholestan-3-one was found to be rapidly converted into 5β-cholestane-3α,7α-diol in the presence of 20,000 ×g supernatant fluid. The results suggest that a major pathway in the conversion of cholesterol into chenodeoxycholic acid might be: cholesterol → cholest-5-ene-3β,7α-diol → 7α-hydroxychole...