Deoxycholic acid (T3D4961)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2014-10-02 18:57:11 UTC
Update Date2018-03-21 17:46:17 UTC
Accession NumberT3D4961
Identification
Common NameDeoxycholic acid
ClassSmall Molecule
DescriptionDeoxycholic acid is a secondary bile acid produced in the liver and is usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion. Bile acids are steroid acids found predominantly in the bile of mammals. The distinction between different bile acids is minute, and depends only on the presence or absence of hydroxyl groups on positions 3, 7, and 12. Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids recirculate through the liver, bile ducts, small intestine, and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH, and consequently require a carrier for transport across the membranes of the enterohepatic tissues. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g. membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues (PMID: 11316487, 16037564, 12576301, 11907135). When present in sufficiently high levels, deoxycholic acid can act as a hepatotoxin, a metabotoxin, and an oncometabolite. A hepatotoxin causes damage to the liver or liver cells. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. An oncometabolite is a compound, when present at chronically high levels, that promotes tumour growth and survival. Among the primary bile acids, cholic acid is considered to be the least hepatotoxic while deoxycholic acid is the most hepatoxic (PMID: 1641875). The liver toxicity of bile acids appears to be due to their ability to peroxidate lipids and to lyse liver cells. High bile acid levels lead to the generation of reactive oxygen species and reactive nitrogen species, disruption of the cell membrane and mitochondria, induction of DNA damage, mutation and apoptosis, and the development of reduced apoptosis capability upon chronic exposure (PMID: 24884764). Chronically high levels of deoxycholic acid are associated with familial hypercholanemia. In hypercholanemia, bile acids, including deoxycholic acid, are elevated in the blood. This disease causes liver damage, extensive itching, poor fat absorption, and can lead to rickets due to lack of calcium in bones. The deficiency of normal bile acids in the intestines results in a deficiency of vitamin K, which also adversely affects clotting of the blood. The bile acid ursodiol (ursodeoxycholic acid) can improve symptoms associated with familial hypercholanemia. Chronically high levels of deoxycholic acid are also associated with several forms of cancer including colon cancer, pancreatic cancer, esophageal cancer, and many other GI cancers.
Compound Type
  • Animal Toxin
  • Metabolite
  • Natural Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
5b-Cholanic acid-3a,12a-diol
5b-Deoxycholate
5b-Deoxycholic acid
7-Deoxycholate
7-Deoxycholic acid
Cholerebic
Cholorebic
Degalol
Deoxy-Cholate
Deoxy-Cholic acid
Deoxycholatate
Deoxycholate
Deoxycholatic acid
Chemical FormulaC24H40O4
Average Molecular Mass392.572 g/mol
Monoisotopic Mass392.293 g/mol
CAS Registry Number83-44-3
IUPAC Name(4R)-4-[(2S,5R,14R,15R,16S)-5,16-dihydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]pentanoic acid
Traditional Name(4R)-4-[(2S,5R,14R,15R,16S)-5,16-dihydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]pentanoic acid
SMILESC[C@H](CCC(O)=O)[C@H]1CCC2C3CCC4C[C@H](O)CC[C@]4(C)C3C[C@H](O)[C@]12C
InChI IdentifierInChI=1S/C24H40O4/c1-14(4-9-22(27)28)18-7-8-19-17-6-5-15-12-16(25)10-11-23(15,2)20(17)13-21(26)24(18,19)3/h14-21,25-26H,4-13H2,1-3H3,(H,27,28)/t14-,15?,16-,17?,18-,19?,20?,21+,23+,24-/m1/s1
InChI KeyInChIKey=KXGVEGMKQFWNSR-TXNNXGFQSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dihydroxy bile acids, alcohols and derivatives. Dihydroxy bile acids, alcohols and derivatives are compounds containing or derived from a bile acid or alcohol, and which bears exactly two carboxylic acid groups.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassBile acids, alcohols and derivatives
Direct ParentDihydroxy bile acids, alcohols and derivatives
Alternative Parents
Substituents
  • Dihydroxy bile acid, alcohol, or derivatives
  • 3-alpha-hydroxysteroid
  • Hydroxysteroid
  • 12-hydroxysteroid
  • 3-hydroxysteroid
  • Cyclic alcohol
  • Secondary alcohol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginNot Available
Cellular Locations
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Erythrocyte
  • Fibroblasts
  • Intestine
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point171 - 174 °C
Boiling PointNot Available
Solubility0.0436 mg/mL
LogP3.5
Predicted Properties
PropertyValueSource
Water Solubility0.017 g/LALOGPS
logP3.3ALOGPS
logP3.79ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)4.65ChemAxon
pKa (Strongest Basic)-0.35ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area77.76 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity109.2 m³·mol⁻¹ChemAxon
Polarizability46.62 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0009000000-ab9ac299290313e78fe42016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-006x-1009000000-6444232cac6b7a24dd962016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-9006000000-b2f4c82d34550211259c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-056r-0009000000-db8bf3905980e8620f122016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-056r-0009000000-6a632f1c8fbb19a314cb2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-4219000000-29a9a2c5d3d148fca2022016-08-01View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsChronically high levels of deoxycholic acid are associated with several forms of cancer including colon cancer.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB03619
HMDB IDHMDB00626
PubChem Compound ID222528
ChEMBL IDNot Available
ChemSpider ID193196
KEGG IDC04483
UniProt IDNot Available
OMIM ID
ChEBI ID28834
BioCyc IDNot Available
CTD IDD003840
Stitch IDNot Available
PDB IDDXC
ACToR IDNot Available
Wikipedia LinkDeoxycholic acid
References
Synthesis ReferenceNot Available
MSDST3D4961.pdf
General References
  1. Berr F, Stellaard F, Pratschke E, Paumgartner G: Effects of cholecystectomy on the kinetics of primary and secondary bile acids. J Clin Invest. 1989 May;83(5):1541-50. [2708522 ]
  2. Yamaga N, Adachi K, Shimizu K, Miyake S, Sumi F, Miyagawa I, Goto H: Bile acids of patients with renal failure receiving chronic hemodialysis. Steroids. 1986 Nov-Dec;48(5-6):427-38. [3445292 ]
  3. Stellaard F, Paumgartner G, van Berge Henegouwen GP, van der Werf SD: Determination of deoxycholic acid pool size and input rate using [24-13C]deoxycholic acid and serum sampling. J Lipid Res. 1986 Nov;27(11):1222-5. [3559388 ]
  4. Andersen RB, Bruusgaard A: Effect of the common bile acids on the fibrin/fibrinogen fragments in rheumatoid synovial fluid. A possible clue to the ameliorating effect of jaundice in rheumatoid arthritis. Scand J Rheumatol. 1975;4(3):158-64. [52191 ]
  5. Deleze G, Paumgartner G, Karlaganis G, Giger W, Reinhard M, Sidiropoulos D: Bile acid pattern in human amniotic fluid. Eur J Clin Invest. 1978 Feb;8(1):41-5. [417931 ]
  6. Beher WT, Gabbard A, Norum RA, Stradnieks S: Effect of blood high density lipoprotein cholesterol concentration on fecal steroid excretion in humans. Life Sci. 1983 Jun 27;32(26):2933-7. [6865641 ]
  7. Nobuoka A, Takayama T, Miyanishi K, Sato T, Takanashi K, Hayashi T, Kukitsu T, Sato Y, Takahashi M, Okamoto T, Matsunaga T, Kato J, Oda M, Azuma T, Niitsu Y: Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid. Gastroenterology. 2004 Aug;127(2):428-43. [15300575 ]
  8. Rudi J, Schonig T, Stremmel W: -Therapy with ursodeoxycholic acid in primary biliary cirrhosis in pregnancy-. Z Gastroenterol. 1996 Mar;34(3):188-91. [8650973 ]
  9. Heikkinen J, Maentausta O, Tuimala R, Ylostalo P, Janne O: Amniotic fluid bile acids in normal and pathologic pregnancy. Obstet Gynecol. 1980 Jul;56(1):60-4. [7383489 ]
  10. Duret G, Delcour AH: Deoxycholic acid blocks vibrio cholerae OmpT but not OmpU porin. J Biol Chem. 2006 Jul 21;281(29):19899-905. Epub 2006 May 2. [16670088 ]
  11. Costarelli V, Sanders TA: Plasma deoxycholic acid concentration is elevated in postmenopausal women with newly diagnosed breast cancer. Eur J Clin Nutr. 2002 Sep;56(9):925-7. [12209383 ]
  12. Stadler J, Yeung KS, Furrer R, Marcon N, Himal HS, Bruce WR: Proliferative activity of rectal mucosa and soluble fecal bile acids in patients with normal colons and in patients with colonic polyps or cancer. Cancer Lett. 1988 Jan;38(3):315-20. [3349450 ]
  13. Tadano T, Kanoh M, Matsumoto M, Sakamoto K, Kamano T: Studies of serum and feces bile acids determination by gas chromatography-mass spectrometry. Rinsho Byori. 2006 Feb;54(2):103-10. [16548228 ]
  14. Salen G, Tint GS, Eliav B, Deering N, Mosbach EH: Increased formation of ursodeoxycholic acid in patients treated with chenodeoxycholic acid. J Clin Invest. 1974 Feb;53(2):612-21. [11344576 ]
  15. St-Pierre MV, Kullak-Ublick GA, Hagenbuch B, Meier PJ: Transport of bile acids in hepatic and non-hepatic tissues. J Exp Biol. 2001 May;204(Pt 10):1673-86. [11316487 ]
  16. Claudel T, Staels B, Kuipers F: The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2020-30. Epub 2005 Jul 21. [16037564 ]
  17. Chiang JY: Bile acid regulation of hepatic physiology: III. Bile acids and nuclear receptors. Am J Physiol Gastrointest Liver Physiol. 2003 Mar;284(3):G349-56. [12576301 ]
  18. Davis RA, Miyake JH, Hui TY, Spann NJ: Regulation of cholesterol-7alpha-hydroxylase: BAREly missing a SHP. J Lipid Res. 2002 Apr;43(4):533-43. [11907135 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. G-protein coupled bile acid receptor 1
General Function:
G-protein coupled bile acid receptor activity
Specific Function:
Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macrophage functions by bile acids.
Gene Name:
GPBAR1
Uniprot ID:
Q8TDU6
Molecular Weight:
35247.795 Da
References
  1. Yoneno K, Hisamatsu T, Shimamura K, Kamada N, Ichikawa R, Kitazume MT, Mori M, Uo M, Namikawa Y, Matsuoka K, Sato T, Koganei K, Sugita A, Kanai T, Hibi T: TGR5 signalling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease. Immunology. 2013 May;139(1):19-29. doi: 10.1111/imm.12045. [23566200 ]
Target Details
2. Glutathione S-transferase P
General Function:
S-nitrosoglutathione binding
Specific Function:
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
Gene Name:
GSTP1
Uniprot ID:
P09211
Molecular Weight:
23355.625 Da
References
  1. Nobuoka A, Takayama T, Miyanishi K, Sato T, Takanashi K, Hayashi T, Kukitsu T, Sato Y, Takahashi M, Okamoto T, Matsunaga T, Kato J, Oda M, Azuma T, Niitsu Y: Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid. Gastroenterology. 2004 Aug;127(2):428-43. [15300575 ]
Target Details
3. Bile acid receptor
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
Gene Name:
NR1H4
Uniprot ID:
Q96RI1
Molecular Weight:
55913.915 Da
References
  1. Fujino T, Une M, Imanaka T, Inoue K, Nishimaki-Mogami T: Structure-activity relationship of bile acids and bile acid analogs in regard to FXR activation. J Lipid Res. 2004 Jan;45(1):132-8. Epub 2003 Sep 16. [13130122 ]