Hyodeoxycholic Acid - Metabolism

Metabolism

In rat intestinal microflora hyodeoxycholic acid is produced by a Gram-positive rod—termed HDCA-1—from several isomers of hyocholic acid and muricholic acid. In pigs with a normal gastrointestinal flora the majority of hyodeoxycholic acid found in bile is of secondary nature, but a small amount was also found in germ free pigs, which supports the hypothesis that HDCA may be a primary bile acid in this species. In healthy humans only traces of HDCA have been found in urine, but in patients with cholestatic liver disease or intestinal malabsorption a significant amount has been found excreted.

Hyodeoxycholic acid undergoes glucuronidation in human liver and kidneys. Glucuronidation of hyodeoxycholic and hyocholic acids was observed to occur extensively at the 6α-hydroxyl group, unlike primary bile acids which form 3α-hydroxy-linked glucuronides. This suggests an important pathway for the elimination of toxic and cholestatic bile acids, e.g. lithocholic and chenodeoxycholic acids which can form hyodeoxycholic and hyocholic acids, respectively, after 6α-hydroxilation. The enzyme family responsible for glucosidation of hyodeoxycholic acid in human liver is UDP-glucuronosyltransferase. Both the UGT2B4 and UGT2B7 isoforms are able to glucuronidate HDCA. This is an example of redundancy in protection against harmful endogenous compounds provided by UGT isoforms, which present distinct but frequently overlapping substrate specificity. A common amino-acid residue that confers these two isoforms specificity to HDCA has been identified in 2006.

Animal model studies support the concept that bile acids may play a role in the development of colon cancer. Deoxycholic acid (DCA) is believed to be tumor promoter, while ursodeoxycholic acid (UDCA) was found to suppress the development of colon tumors. The mechanism that accounts for this difference in function is not clear. In vitro studies found that DCA induces apoptosis in some colon cancer cell lines, while UDCA arrests cell proliferation without inducing apoptosis. In these studies HDCA exhibited biological activity that is intermediate to DCA and UDCA, arresting growth for a time, but causing apoptosis after extended exposure.