Biosynthesis of bile acids in man. An in vivo evaluation of the conversion of R and S 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic and 3 alpha, 7 alpha, 12 alpha-24 xi-tetrahydroxy-5 beta-cholestanoic acids to cholic acid.
1981
Abstract In vivo studies were carried out on three bile fistula patients to further elucidate the side chain oxidation pathways from C-27 bile acids to cholic acid in man. Two patients each received (25-R)- and (25-S)-3 alpha, 7 alpha,-12 alpha-trihydroxy-5 beta-[7 beta-3H]cholestanoic acid (THCA) on consecutive days and three patients wee administered 3 alpha, 7 alpha, 12 alhpa, 24 xi-tetrahydroxy-5 beta-[7 beta-3H]cholestanoic acid (varanic acid). The varanic acid was biosynthetically prepared with rat liver microsomes and was probably the 24 alpha isomer. The patients efficiently (84 to 97%) converted both (R)- and (S)-THCA to cholic acid. There was no apparent significant difference in the ability of either (R)- or (S)-THCA to form cholic acid. Varanic acid was poorly converted (20 to 27%) to cholic acid in all three patients. From 49 to 75% of the administered 3H activity was recovered in the bile as other labeled products. The bulk (30 to 35%) of this 3H activity was identified by thin layer chromatography as varanic acid. The rate of conversion of (R)-THCA, (S)-THCA, and varanic acid was extremely rapid in all three patients with a t 1/2 of 35 to 74 min. The findings suggest that (a) the stereospecific configuration at C-25 of THCA has no significant effect on the efficiency of side chain oxidation to cholic acid; and (b) side chain cleavage pathways may exist which do not pass through varanic acid, or the oxidation of varanic acid in man is highly stereospecific with respect to the hydroxyl group at C-24. To prove the latter, it will be necessary to compare the metabolism of the 24 alpha and 24 beta isomers of varanic acid.
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