The hepatic metabolism and the choleretic effect of
homochenodeoxycholic acid, the C25 homologue of
chenodeoxycholic acid, were investigated in the hamster. After
intravenous administration of 3H-labeled
homochenodeoxycholic acid into
biliary fistula hamsters, more than 80% of the radioactivity was recovered in bile in 4 h. A relatively small proportion of
homochenodeoxycholic acid was present in bile as the
taurine (22%) or
glycine (4%) conjugate. However, more than 70% of the administered compound was biotransformed into C23
bile acids. The major C23 metabolites in bile were norchenodeoxycholic
acid (17%), tauronorchenodeoxycholic
acid (33%), and a trihydroxy norbile
acid (identified as 3 alpha, 5 beta, 7 alpha-trihydroxy-24-nor-5 beta-cholan-23-oic
acid, 19%). Small amounts (< 5%) of
sulfate(s) and
glucuronide(s) were also detected.
Homochenodeoxycholic acid, when infused intravenously into the hamster, produced a striking choleresis. The increase in bile flow after infusion of this compound was 6- to 7-times that induced by
chenodeoxycholic acid. The apparent choleretic activity of
homochenodeoxycholic acid, 181 microliters/mumol, was much greater than that of
chenodeoxycholic acid, 11 microliters/mumol. In conclusion,
homochenodeoxycholic acid induced a hypercholeresis of the same order of magnitude as norchenodeoxycholic
acid, presumably because considerable proportions of this compound were degraded to the hypercholeretic norchenodeoxycholic
acid via beta-oxidation in the liver.