Chenodeoxycholic acid structure and its applications

Chenodeoxycholic acid (CDCA;also known as chenodeoxycholic acid,chenodelic acid,and 3α,7α-dihydroxy-5β-cholan-24-oic acid) is a bile acid.The salt of this carboxylic acid is called chenodeoxycholate.Chenodeoxycholic acid is one of the main bile acids.It was first isolated from the bile of domestic geese, which gave it the "cheno" part of its name (Greek: χήν = goose).

Structure 

Chenodeoxycholic acid and cholic acid are the two main bile acids in the human body.Chenodeoxycholic acid has two hydroxyl groups,which can be modified by adding another hydroxyl group to produce cholic acid.Some other mammals contain muricholic acid or deoxycholic acid instead of chenodeoxycholic acid.It exists as a white crystalline substance that is insoluble in water but soluble in alcohol and acetic acid, melting at 165–167 °C.

Biosynthesis and Function

Chenodeoxycholic acid is synthesized from cholesterol in the liver through several enzymatic steps.Like other bile acids,it can combine with taurine or glycine to form taurochenodeoxycholate or glycochenodeoxycholate.Conjugation results in lower pKa.This causes conjugated bile acids to become ionized at normal pH in the gut and stay in the GI tract until they reach the ileum to be reabsorbed.CDCA and other bile acids form micelles that facilitate lipid digestion.After absorption,it is taken up by the liver and re-secreted for enterohepatic circulation.Unabsorbed CDCA can be metabolized by bacteria in the colon to form a secondary bile acid,lithocholic acid,or the epimer,ursodeoxycholic acid.CDCA is the most potent natural bile acid that stimulates the nuclear bile acid receptor farnesoid X receptor (FXR).The transcription of many genes is activated by FXR,including FGF19 and SHP.

Therapeutic application

Gallstones

CDCA has been used as a drug therapy to dissolve gallstones.Oral bile acid drug therapy has been used in patients with small cholesterol gallstones,as well as in patients with larger cholesterol gallstones who are unable or unwilling to undergo surgery.CDCA treatment can cause diarrhea,mildly reversible liver injury,and a small increase in plasma cholesterol levels.Xanthomatosis of the Cerebral Tendon.CDCA can be used in the treatment of tendon xanthomatosis.

Others

CDCA has been used in several other situations.Because of the frequent diarrhea that occurs when CDCA is used for gallstone dissolution,it has been investigated as a possible treatment for constipation and has been shown to accelerate colonic transit and improve bowel function.

Deoxycholic acid

Deoxycholic acid is a bile acid.Deoxycholic acid is one of the secondary bile acids and is a metabolic by-product of gut bacteria.The two main bile acids secreted by the liver are cholic acid and chenodeoxycholic acid.Bacteria metabolize chenodeoxycholic acid to the secondary bile acid lithocholic acid and metabolize cholic acid to deoxycholic acid.There are other secondary bile acids,such as ursodeoxycholic acid.Deoxycholic acid is soluble in alcohol and acetic acid.When pure,it takes the form of a white to off-white crystalline powder.Deoxycholic acid has been used in various fields of human medicine since its discovery.In humans,deoxycholic acid is used to emulsify fats for absorption in the intestine.It has been licensed as an emulsifier in the food industry,but it is no longer common.In vitro,it is used in the experimental basis of choleretic agents and also in the prevention and dissolution of gallstones.Deoxycholic acid was used as a mild detergent for the separation of membrane-associated proteins.The critical micelle concentration of deoxycholic acid is approximately 2.4–4 mM.Sodium deoxycholate,the sodium salt of deoxycholic acid,is commonly used as a biodetergent to lyse cells and dissolve cellular and membrane components.Sodium deoxycholate mixed with phosphatidylcholine is used in mesotherapy injections to generate lipolysis and has been used as an alternative to surgical excision in the treatment of lipomas.In general,deoxycholate and bile acid derivatives are being actively studied as binding structures for nanotechnology.They also found application as photoresist elements in microlithography.