Chenodeoxycholic acid

Chenodeoxycholic acid

Names
IUPAC names chenodiol OR 3α,7α-dihydroxy-5β-cholanic acid OR 5β-cholanic acid-3α,7α-diol OR (R)-((3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy -10,13-dimethylhexadecahydro- 1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid
Identifiers
CAS Number	474-25-9
ChEBI	CHEBI:16755
ChEMBL	ChEMBL240597
ChemSpider	9728
DrugBank	DB06777
IUPHAR/BPS	608
Jmol 3D model	Interactive image
KEGG	C02528
UNII	0GEI24LG0J
InChI InChI=1S/C24H40O4/c1-14(4-7-21(27)28)17-5-6-18-22-19(9-11-24(17,18)3)23(2)10-8-16(25)12-15(23)13-20(22)26/h14-20,22,25-26H,4-13H2,1-3H3,(H,27,28)/t14-,15+,16-,17-,18+,19+,20-,22+,23+,24-/m1/s1 Key: RUDATBOHQWOJDD-BSWAIDMHSA-N InChI=1/C24H40O4/c1-14(4-7-21(27)28)17-5-6-18-22-19(9-11-24(17,18)3)23(2)10-8-16(25)12-15(23)13-20(22)26/h14-20,22,25-26H,4-13H2,1-3H3,(H,27,28)/t14-,15+,16-,17-,18+,19+,20-,22+,23+,24-/m1/s1 Key: RUDATBOHQWOJDD-BSWAIDMHBF
SMILES C[C@H](CCC(=O)O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2[C@@H](C[C@H]4[C@@]3(CC[C@H](C4)O)C)O)C
Properties
Chemical formula	C24H40O4
Molar mass	392.57 g/mol
Melting point	165 to 167 °C (329 to 333 °F; 438 to 440 K)
Pharmacology
ATC code	A05AA01 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Chenodeoxycholic acid (also known as chenodesoxycholic acid, chenocholic acid and 3α,7α-dihydroxy-5β-cholan-24-oic acid) is a bile acid. It occurs as a white crystalline substance insoluble in water but soluble in alcohol and acetic acid, with melting point at 165-167 °C. Salts of this carboxylic acid are called chenodeoxycholates. Chenodeoxycholic acid is one of the main bile acids produced by the liver.^[1]

It was first isolated from the bile of the domestic goose, which gives it the "cheno" portion of its name (Greek: χήν = goose).^[2]

Chenodeoxycholic acid and cholic acid are the two primary bile acids in humans. Some other mammals have muricholic acid or deoxycholic acid rather than chenodeoxycholic acid.^[1]

Chenodeoxycholic acid is synthesized in the liver from cholesterol by a process which involves several enzymatic steps.^[1] Like other bile acids, it can be conjugated in the liver with taurine or glycine, forming taurochenodeoxycholate or glycochenodeoxycholate. Conjugation results in a lower pKa. This means the conjugated bile acids are ionized at the usual pH in the intestine and will stay in the gastrointestinal tract until reaching the ileum where most will be reabsorbed. Bile acids form micelles which facilitate lipid digestion. After absorption, they are taken up by the liver and resecreted, so undergoing an enterohepatic circulation. Unabsorbed chenodeoxycholic acid can be metabolised by bacteria in the colon to form the secondary bile acid known as lithocholic acid.

Choendeoxycholic acid is the most potent natural bile acid at stimulating the nuclear bile acid receptor, farnesoid X receptor (FXR).^[3] The transcription of many genes is activated by FXR.

Therapeutic applications

Chenodeoxycholic acid has been used as medical therapy to dissolve gallstones.^[4]

Chenodeoxycholic acid can be used in the treatment of cerebrotendineous xanthomatosis.^[5]

The Australian biotechnology company Giaconda has tested a treatment for Hepatitis C infection that combines chenodeoxycholic acid with bezafibrate.^[6]

As diarrhea is a complication of chenodeoxycholic acid therapy, it has also been used to treat constipation.^[7][8]

In supramolecular chemistry, molecular tweezers based on a chenodeoxycholic acid scaffold is a urea receptor that can contain anions in its binding pocket in order of affinity: H₂PO₄⁻ (dihydrogen phosphate) > Cl⁻ > Br⁻ > I⁻ reflecting their basicities (tetrabutylammonium counter ion).^[9]

See Also

• Ursodeoxycholic acid - an enantiomer
• Hyodeoxycholic acid - an isomer

References

1. Russell DW (2003). "The enzymes, regulation, and genetics of bile acid synthesis". Annu. Rev. Biochem. 72: 137–74. doi:10.1146/annurev.biochem.72.121801.161712. PMID 12543708.
2. Carey MC (December 1975). "Editorial: Cheno and urso: what the goose and the bear have in common". N. Engl. J. Med. 293 (24): 1255–7. doi:10.1056/NEJM197512112932412. PMID 1186807.
3. Parks DJ, Blanchard SG, Bledsoe RK; et al. (May 1999). "Bile acids: natural ligands for an orphan nuclear receptor". Science 284 (5418): 1365–8. doi:10.1126/science.284.5418.1365. PMID 10334993.
4. Thistle JL, Hofmann AF (September 1973). "Efficacy and specificity of chenodeoxycholic acid therapy for dissolving gallstones". N. Engl. J. Med. 289 (13): 655–9. doi:10.1056/NEJM197309272891303. PMID 4580472.
5. Berginer VM, Salen G, Shefer S (December 1984). "Long-term treatment of cerebrotendinous xanthomatosis with chenodeoxycholic acid". N. Engl. J. Med. 311 (26): 1649–52. doi:10.1056/NEJM198412273112601. PMID 6504105.
6. Giaconda. "Press release". Retrieved 5 April 2014.
7. Bazzoli F, Malavolti M, Petronelli A, Barbara L, Roda E (1983). "Treatment of constipation with chenodeoxycholic acid". J. Int. Med. Res. 11 (2): 120–3. PMID 6852359.
8. Rao AS, Wong BS, Camilleri M; et al. (November 2010). "Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis". Gastroenterology 139 (5): 1549–58, 1558.e1. doi:10.1053/j.gastro.2010.07.052. PMC 3189402. PMID 20691689.
9. Ki Soo Kim, Hong-Seok Kim Molecular Tweezer Based on Chenodeoxycholic Acid:Synthesis, Anion Binding Properties. Bulletin of the Korean Society 1411-1413 2004 Article