Bile Acids

Abstract

a-Muricholic acid (3a, 6p, 7a-trihydroxy-5@-cholanoic acid)' and ,&muricholic acid (3~) 6/I, 7@-trihydroxy-5@-cholanoic acid), which are constituents of rat bile (2), are metabolites of chenodeoxycholic acid in both the rat (2-5) and the mouse (6).The a! acid was found to be present in slightly higher concentration than the p acid in rat bile (2).It was also observed that the latter acid is the principal bile acid in the urine of surgically jaundiced rats (4).These and other observations have led to the suggestion that a-muricholic acid may be an intermediate in the formation of /?-muricholic acid and that the inversion of the 'I-hydroxyl group may proceed through the formation of a 7-keto intermediate (7, 8).The metabolic conversion of the cy acid to the @ acid in the rat was reported by Samuelsson (8) and Cherayil et al. ( 9).This paper reports our study on the metabolism of cr-muricholic acid in surgically jaundiced rats.During the course of the identification of metabolites of cr-muricholic acid, it became apparent that at least one new radioactive compound was present in the urine.This led to a consideration of the possible reactions of the ketol postulated to be an intermediate between LL-and P-muricholic acids.Since it appeared likely that ring B which bears the ketolic structure might be ruptured (lo), the seco la&one was prepared.It proved to be identical with the unknown radioactive compound present in the urine.EXPERIMENTAL PROCEDURE'! Synthesis of or-Muricholic Acid-@-P-a-Muricholic acid was prepared by a procedure previously described (11).After