Formation and Metabolism of some Δ4‐Cholestenols in the Rat

The synthesis of unlabeled and tritium‐labeled cholest‐4‐ene‐3α, 7α‐diol and cholest‐4‐ene 3β, 7α‐diol is described. Both compounds were found to be efficiently converted into cheodeoxycholic acid and cholic acid in the bile fistula rat. The presence in liver of microsomal and soluble Δ4‐3‐hydroxysteroid dehydrogenases active on Δ4‐3‐hydroxysteroids of the C27 series was demonstrated. The soluble dehydrogenase(s) was more active on the Δ4‐3α‐hydroxysteroids than on the Δ4‐3β‐hydroxysteroids. The microsomal fraction contained dehydrogenase(s) capable of oxidizing both the Δ4‐3α‐hydroxysteroids and the Δ4‐3α‐hydroxysteroids in the presence of NAD or NADP, NAD being preferred. No significant conversion of cholest‐5‐ene‐3β, 7α‐diol to cholest‐4‐ene‐3β, 7α‐diol could be shown nor could any direct saturation of the double bond in cholest‐4‐ene‐3α, 7α‐diol or that in cholest‐4‐ene‐3α, 7α,12α‐triol be shown. Cholest‐4‐ene‐3α, 7α‐diol was hydroxylated in the 12α‐position more efficiently than cholest‐4‐ene‐3β, 7α‐diol. It is suggested that the Δ4‐cholestenols are converted to bile acids by first being oxidized to the corresponding Δ4‐3‐ketosteroids.