Steroid Metabolism in Rats Given [1‐ 2 H 2 ]Ethanol

The formation and metabolism of 3‐hydroxycholanoic acids were studied in bile fistula rats. When 3‐oxo‐4‐cholenoic acid was given, 3α‐hydroxy‐5α‐cholanoic acid was the major metabolite. Judging from the behaviour on chromatography and solvolysis, most of this metabolite was excreted as a sulphate of the conjugated bile acid. The major part of the 3‐hydroxycholanoic acids excreted after injection of 3β‐hydroxy‐5α‐cholanoic acid was also present in this form. Epimerization of 3β‐hydroxy‐5α‐cholanoic acid was very limited and the relative amount of 3α epimer was much higher in the “non‐sulphate” than in the “sulphate” fraction. In contrast, epimerization of administered 3β‐hydroxy‐5β‐cholanoic acid was complete, and only 10–20% of the metabolites were excreted in the “sulphate” form. The inversion of the hydroxyl group of 3β‐hydroxy‐5β‐cholanoic acid was complete also during the metabolism of ethanol. Administration of pyrazole resulted in partial inhibition of the epimerization of both 3β‐hydroxy‐5β‐and 3β‐hydroxy‐5α‐cholanoic acids. Since alcohol dehydrogenase is specific for the 3β‐hydroxy‐5β‐steroid structure this indicates that alcohol dehydrogenase is not the only 3β‐hydroxysteroid dehydrogenase inhibited by pyrazole. Deuterium was incorporated into the 3β position of lithocholic acid during the metabolism of [1‐ 2 H 2 ]ethanol. The deuterium excess was about 12 atoms % when lithocholic acid was formed by epimerization of 3β‐hydroxy‐5β‐cholanoic acid, and about 5 atoms % when lithocholic acid was given. This indicates that about 40% of the lithocholic acid underwent oxidoreduction before being excreted in bile. The deuterium excess in the 3β position of 3α‐hydroxy‐5α‐cholanoic acid formed from 3‐oxo‐4‐cholenoic acid was about 14 atoms %. No deuterium was found in the 5α position. This indicates that different coenzyme pools were utilized in the reductions of the oxo group and the double bond.