On the Conversion of Cholestanol into Allocholic Acid in Rat Liver

The early steps in the conversion of cholestanol into allocholic acid were studied in homogenates of rat liver. The 20000 ×g supernatant fluid was found to catalyze 7α‐hydroxylation of cholestanol. Under the same conditions 7α‐hydroxylation of 5α‐cholestan‐3α‐ol and 5α‐cholestan‐3‐one was insignificant. The microsomal fraction fortified with NAD catalyzed oxidation of 5α‐cholestande‐3β,7α‐diol into 7α‐hydroxy‐5aL‐cholestan‐3‐one. The 100 000 ×g supernatant fluid catalyzed reduction of 7α‐hydroxy‐5α‐cholestan‐3‐one into 5α‐cholestane‐3α,7α‐diol. The same reaction was effected by a partially purified 3α‐hydroxysteroid dehydrogenase from rat liver in the presence of NADPH. The microsomal fraction fortified with NADPH catalyzed 12α‐hydroxylation of 5α‐cholestane‐3α, 7α‐diol at a rate about six times faster than that with either 5α‐cholestane‐3β,7α‐diol or 7α‐hydroxy‐5α‐cholestan‐3‐one. In rats with a biliary fistula 5α‐cholestane‐3β,7α‐diol and 5α‐cholestane‐3α,7α‐diol were converted into allocholic acid. The results indicate that the main pathway for the conversion of cholestanol into allocholic acid involves the following steps: cholestanl → 5α‐cholestane‐3β,7α‐diol → 7α hydroxy‐5α‐cholestan‐3‐one → 5α‐cholestane‐3α,7α‐diol → 5α‐cholestane‐3α,7α,12α‐triol → allocholic acid.