Utilization of the carbon and hydrogen atoms of ethanol in the biosynthesis of steroids and bile acids.

Abstract

[1‐2H2]Ethanol, [2‐2H3]ethanol and [1‐13C, 1‐2H2]ethanol were administered to bile fistula rats under conditions ensuring a maximal rate of oxidation for about 24 h. Cholesterol, cholic acid, chenodeoxycholic acid and 3β,11β,21‐trihydroxy‐5α‐pregnan‐20‐one were isolated from bile collected at intervals during the experiment. The fraction of molecules containing different numbers of heavy isotope atoms was measured by gas chromatography–mass spectrometry–computer techniques. The results were used to determine the origin of the cholesterol pools used as precursors for the different compounds isolated from bile.The bile acids were found to be formed from a cholesterol pool, the turnover of which was about 5 times more rapid than that of the cholesterol pool used for biliary excretion. The cholesterol pools used for biliary excretion and as corticosterone precursor seemed to be in equilibrium.The acetyl groups derived from ethanol were introduced into the steroids without exchange of hydrogens at C‐2, and the acetyl‐CoA pool used as precursor did not exchange with acetyl groups in e.g. citrate or fatty acids. A difference in incorporation of [2‐2H3]acetyl groups and [1‐13C]acetyl groups was interpreted to be due to an isotope effect. Ethanol contributed about 45% of the acetyl‐CoA pool used as precursor of cholesterol and bile acids.Deuterium from [1‐2H2]ethanol was incorporated in many positions of all the steroids. If it is assumed that the incorporation is mediated by NADPH, the deuterium excess of the hydrogens introduced was about 10 atoms%. The contribution via different pathways of an important part of the hydrogen and carbon atoms in cholesterol, bile acids and corticosteroids provides possible mechanisms by which ethanol may affect the biosynthesis and metabolism of steroids.