Hyodeoxycholic acid, also known as 3α,6α-Dihydroxy-5β-cholan-24-oic acid or HDCA, is a secondary

bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary b ...

, one of the metabolic byproducts of

intestinal bacteria Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut mic ...

. It differs from deoxycholic acid in that the 6α- hydroxyl is in the 12 position in the former. The 6α- hydroxyl group makes HDCA a hydrophilic acid, a property it shares with

hyocholic acid Hyocholic acid or 3α,6α,7α-trihydroxy-5β-cholan-24-oic acid is a bile acid found as one of the main forms in pig, and at low concentrations in other species including humans. Hyocholic acid differs from the primary bile acids found in humans ...

. HDCA is present in mammalian species in different proportions. It is the main acid constituent of hog bile, and for this reason it was used industrially as precursor for steroid synthesis before total synthesis became practical.

Metabolism

In rat intestinal microflora hyodeoxycholic acid is produced by a Gram-positive

rod Rod, Ror, Ród, Rőd, Rød, Röd, ROD, or R.O.D. may refer to: Devices * Birch rod, made out of twigs from birch or other trees for corporal punishment * Ceremonial rod, used to indicate a position of authority * Connecting rod, main, coupling, ...

—termed HDCA-1—from several isomers of

and

muricholic acid Muricholic acids are a group of bile acids found as one of the main forms in mice, which gives them their name, and at low concentrations in other species. Muricholic acids differ from the primary bile acids found in humans, cholic acid and chenode ...

. 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 Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to build ...

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 Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...

. 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 Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

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.

Applications

It was known since 1939 that HDCA could be used to synthesize

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...

. A decade later, an analysis of the composition of hog bile determined that HDCA accounted for approximately 40% of its acid contents. In the 1950s, lacking access to vegetal precursors of steroids, like

diosgenin Diosgenin, a phytosteroid sapogenin, is the product of hydrolysis by acids, strong bases, or enzymes of saponins, extracted from the tubers of ''Dioscorea'' wild yam species, such as the Kokoro. The sugar-free (aglycone) product of such hydrolys ...

, the East German company Jenapharm used hyodeoxycholic acid extracted from hog bile as the sole precursor for steroid synthesis. In the 1980s, hyodeoxycholic acid was investigated for its propensity to prevent cholesterol-induced gallstones in animals fed with a lithogenic diet. Another animal study determined that oral administration of HDCA leads to a decrease in LDL-cholesterol concentration, a strong stimulation of hepatic cholesterol biosynthesis and an excessive loss of cholesterol in feces. Unlike ursodeoxycholic acid, which is an approved drug for the treatment of gallstones, HDCA is not marketed for any medical condition. In supramolecular chemistry a molecular tweezer based on a hyodeoxycholic acid showed a high selectivity the towards the

fluorine Fluorine is a chemical element with the symbol F and atomic number 9. It is the lightest halogen and exists at standard conditions as a highly toxic, pale yellow diatomic gas. As the most electronegative reactive element, it is extremely reacti ...

radical.

References

{{DEFAULTSORT:Hyodeoxycholic Acid Bile acids Cholanes

Metabolism

Applications

See also

References