Biosynthesis of cholic acid in rat liver: Formation of cholic acid from 3α, 7α, 12α-trihydroxy- and 3α, 7α, 12α, 24-tetrahydroxy-5β-cholestanoic acids

Conversion of 3α,7α,12α-trihydroxy-5β-cholestanoic acid into 3α,7α,12α24-tetrahydroxy-5β-cholestanoic and cholic acids was catalyzed either by the mitochondrial fraction fortified with coenzyme A, ATP, MgCl₂ and NAD or by the combination of microsomal fraction and 100,000 x g supernatant fluid fortified with coenzyme A, ATP and NAD. 24-Hydroxylation and formation of cholic acid occurred at similar rates with the 25R- and the 25S-forms of 3α,7α,12α-trihydroxy-5β-cholestanoic acid. The 25R- and 25S-forms of 3α,7α,12α-trihydroxy-and 3α,7α,12α,24-tetrahydroxy-5β-cholestanoic acids were administered to bile fistula rats. Labeled cholic acid was isolated from the bile. The initial specific radioactivity of cholic acid was higher and the disappearance of radioactivity more rapid after administration of 3α,7α,12α-trihydroxy-5β-cholestanoic acid than of 3α,7α,12α,24-tetrahydroxy-5β-cholestanoic acid. The findings are discussed in relation to the assumed pathway for side chain cleavage in cholic acid biosynthesis.