5-BETA-HYDROXYLATION BY THE LIVER - IDENTIFICATION OF 3,5,7-TRIHYDROXY NOR-BILE ACIDS AS NEW MAJOR BIOTRANSFORMATION PRODUCTS OF 3,7-DIHYDROXY NOR-BILE ACIDS IN RODENTS

24-Norursodeoxycholic acid (nor-UDCA), when administered into the anes thetized biliary fistula hamster or injected into the perfusate of an isolated liver, was hydroxylated at C-5 to give 5beta-hydroxynorursode oxycholic acid 2 lpha,5,7beta-trihydroxy-24-nor-5beta-cholan-23-oic ac id), which was secreted into bile mainly as such. Similarly, 24-norche nodeoxycholic acid (nor-CDCA) was 5beta-hydroxylated to give 5beta-hyd roxynorchenodeoxycholic acid 4 pha,5,7alpha-trihydroxy-24-nor-5beta-ch olan-23-oic acid), which was also secreted into bile without appreciab le further biotransformation. The site of hydroxylation was assigned b y C-13 and H-1 NMR and mass spectrometry. 5-Hydroxylation was a major biotransformation pathway at physiological bile acid loads. 5-Hydroxyl ation of UDCA also occurred in the perfused rat liver but to a lesser extent. 5-Hydroxylation of nor-UDCA was not observed in rabbit, dog, o r man, indicating that its formation is species-specific. 5-Hydroxylat ion of nor-CDCA and nor-UDCA is the first reported example of hydroxyl ation of a tertiary carbon atom of bile acids. Nor-dihydroxy bile acid s appear to be useful for the detection of minor hydroxylation pathway s, because their prolonged hepatobiliary retention exposes them repeat edly to hydroxylases present in the hepatobiliary system.