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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-05-13 19:19:41 UTC
HMDB IDHMDB00761
Secondary Accession NumbersNone
Metabolite Identification
Common NameLithocholic acid
DescriptionLithocholic acid is a bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic. A bile acid. Bile acids are steroid acids found predominantly in bile of mammals. The distinction between different bile acids is minute, depends only on 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 ).
Structure
Thumb
Synonyms
ValueSource
(3a,5b)-3-Hydroxy-cholan-24-OateHMDB
(3a,5b)-3-Hydroxy-cholan-24-Oic acidHMDB
3a-Hydroxy-5b-cholan-24-OateHMDB
3a-Hydroxy-5b-cholan-24-Oic acidHMDB
LithocholateHMDB
Chemical FormulaC24H40O3
Average Molecular Weight376.5726
Monoisotopic Molecular Weight376.297745146
IUPAC Name(4R)-4-[(1S,2S,5R,10R,11S,14R,15R)-5-hydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]pentanoic acid
Traditional Nameacid, lithocholic
CAS Registry Number434-13-9
SMILES
[H][C@@]12CC[C@H]([C@H](C)CCC(O)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2C[C@H](O)CC[C@]12C
InChI Identifier
InChI=1S/C24H40O3/c1-15(4-9-22(26)27)19-7-8-20-18-6-5-16-14-17(25)10-12-23(16,2)21(18)11-13-24(19,20)3/h15-21,25H,4-14H2,1-3H3,(H,26,27)/t15-,16?,17-,18+,19-,20+,21+,23+,24-/m1/s1
InChI KeyInChIKey=SMEROWZSTRWXGI-YPLGJCPNSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as monohydroxy bile acids, alcohols and derivatives. These are bile acids, alcohols or any of their derivatives bearing a hydroxyl group.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassBile acids, alcohols and derivatives
Direct ParentMonohydroxy bile acids, alcohols and derivatives
Alternative Parents
Substituents
  • Monohydroxy bile acid, alcohol, or derivatives
  • 3-alpha-hydroxysteroid
  • Hydroxysteroid
  • 3-hydroxysteroid
  • Cyclic alcohol
  • Secondary alcohol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External DescriptorsNot Available
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fat solubilization and Waste products
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point186 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.000377 mg/mLNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.000505 mg/mLALOGPS
logP4.38ALOGPS
logP5.02ChemAxon
logS-5.9ALOGPS
pKa (Strongest Acidic)4.79ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.53 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity107.68 m3·mol-1ChemAxon
Polarizability45.8 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-004i-0009000000-e3a2f64bd8834594c115View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0006-9000000000-b27641d2926e1d3e69edView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-0900000000-d895d3aa84e2458a8507View in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Extracellular
Biofluid Locations
  • Bile
  • Blood
  • Feces
  • Urine
Tissue Location
  • Intestine
  • Liver
Pathways
NameSMPDB LinkKEGG Link
27-Hydroxylase DeficiencySMP00720Not Available
Bile Acid BiosynthesisSMP00035map00120
Cerebrotendinous Xanthomatosis (CTX)SMP00315Not Available
Congenital Bile Acid Synthesis Defect Type IISMP00314Not Available
Congenital Bile Acid Synthesis Defect Type IIISMP00318Not Available
Familial Hypercholanemia (FHCA)SMP00317Not Available
Zellweger SyndromeSMP00316Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BileDetected and Quantified930 (890-960) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.08 +/- 0.02 uMNewborn (0-30 days old)BothNormal details
BloodDetected and Quantified0.33 +/-0.04 uMAdult (>18 years old)BothNormal details
FecesDetected and Quantified1016.60 +/- 647.31 nmol/g of fecesNot SpecifiedNot Specified
Normal
details
UrineDetected and Quantified0.16 (0.10-0.20) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified1.5 (0.5-3.0) uMAdult (>18 years old)Both
Biliary cirrhosis
details
BloodDetected and Quantified0.11 +/- 0.04 uMNewborn (0-30 days old)BothExtrahepatic biliary atresia (EHBA) details
BloodDetected and Quantified0.11 +/- 0.02 uMAdult (>18 years old)Both
Cystic fibrosis
details
BloodDetected and Quantified0.16 +/- 0.07 uMChildren (1-13 years old)BothCystic fibrosis details
FecesDetected but not QuantifiedNot ApplicableNot SpecifiedNot Specified
Recurrent Clostridium difficile infection
details
UrineDetected and Quantified0.32 (0.10-0.52) umol/mmol creatinineAdult (>18 years old)Both
Biliary cirrhosis
details
UrineDetected and Quantified1.1 (0.41-2.4) umol/mmol creatinineAdult (>18 years old)Both
Biliary cirrhosis
details
Associated Disorders and Diseases
Disease References
Biliary atresia
  1. Gustafsson J, Alvelius G, Bjorkhem I, Nemeth A: Bile acid metabolism in extrahepatic biliary atresia: lithocholic acid in stored dried blood collected at neonatal screening. Ups J Med Sci. 2006;111(1):131-6. [16553252 ]
Cystic fibrosis
  1. Smith JL, Lewindon PJ, Hoskins AC, Pereira TN, Setchell KD, O'Connell NC, Shepherd RW, Ramm GA: Endogenous ursodeoxycholic acid and cholic acid in liver disease due to cystic fibrosis. Hepatology. 2004 Jun;39(6):1673-82. [15185309 ]
Primary biliary cirrhosis
  1. Batta AK, Arora R, Salen G, Tint GS, Eskreis D, Katz S: Characterization of serum and urinary bile acids in patients with primary biliary cirrhosis by gas-liquid chromatography-mass spectrometry: effect of ursodeoxycholic acid treatment. J Lipid Res. 1989 Dec;30(12):1953-62. [2621422 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022230
KNApSAcK IDNot Available
Chemspider ID9914991
KEGG Compound IDC03990
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB00761
Metagene LinkHMDB00761
METLIN ID209
PubChem Compound11740284
PDB IDNot Available
ChEBI ID16325
References
Synthesis ReferenceXu, Zhengbang; Li, Kaixi; Zhao, Huaming. Synthesis of lithocholic acid by Huang-Min-Lon modification in the presence of crown ether. Sichuan Daxue Xuebao, Ziran Kexueban (1992), 29(4), 527-9.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. Greco AV, Mingrone G: Serum bile acid concentrations in mild liver cirrhosis. Clin Chim Acta. 1993 Nov 30;221(1-2):183-9. [8149635 ]
  8. Kitahara M, Sakata S, Sakamoto M, Benno Y: Comparison among fecal secondary bile acid levels, fecal microbiota and Clostridium scindens cell numbers in Japanese. Microbiol Immunol. 2004;48(5):367-75. [15215624 ]
  9. Dew MJ, van Berge Henegouwen GP, Huybregts AW, Allan RN: Hepatotoxic effect of bile acids in inflammatory bowel disease. Gastroenterology. 1980 Jun;78(6):1393-401. [7372059 ]
  10. Ceryak S, Bouscarel B, Fromm H: Comparative binding of bile acids to serum lipoproteins and albumin. J Lipid Res. 1993 Oct;34(10):1661-74. [8245717 ]
  11. Eklund A, Norlander A, Norman A: Bile acid synthesis and excretion following release of total extrahepatic cholestasis by percutaneous transhepatic drainage. Eur J Clin Invest. 1980 Oct;10(5):349-55. [6777167 ]
  12. Balistreri WF, Suchy FJ, Farrell MK, Heubi JE: Pathologic versus physiologic cholestasis: elevated serum concentration of a secondary bile acid in the presence of hepatobiliary disease. J Pediatr. 1981 Mar;98(3):399-402. [7205448 ]
  13. Fouin-Fortunet H, Le Quernec L, Erlinger S, Lerebours E, Colin R: Hepatic alterations during total parenteral nutrition in patients with inflammatory bowel disease: a possible consequence of lithocholate toxicity. Gastroenterology. 1982 May;82(5 Pt 1):932-7. [6800873 ]
  14. Hofmann AF: [Enterohepatic circulation of bile acids and biliary lipid secretion] Minerva Med. 1977 Sep 19;68(43):3011-7. [409965 ]
  15. Loof L, Wengle B: Enzymatic sulphation of bile salts in human liver. Biochim Biophys Acta. 1978 Sep 28;530(3):451-60. [698243 ]
  16. Tinker LF, Schneeman BO, Davis PA, Gallaher DD, Waggoner CR: Consumption of prunes as a source of dietary fiber in men with mild hypercholesterolemia. Am J Clin Nutr. 1991 May;53(5):1259-65. [1850578 ]
  17. Farrell GC, Duddy SK, Kass GE, Llopis J, Gahm A, Orrenius S: Release of Ca2+ from the endoplasmic reticulum is not the mechanism for bile acid-induced cholestasis and hepatotoxicity in the intact rat liver. J Clin Invest. 1990 Apr;85(4):1255-9. [2318979 ]
  18. 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 ]
  19. 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 ]
  20. 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 ]
  21. 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 ]

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Converts progesterone to its inactive form, 20-alpha-dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.
Gene Name:
AKR1C1
Uniprot ID:
Q04828
Molecular weight:
36788.02
General function:
Involved in oxidoreductase activity
Specific function:
Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha-DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.
Gene Name:
AKR1C2
Uniprot ID:
P52895
Molecular weight:
15747.91
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
Reactions
Lithocholic acid + NADPH + Oxygen → Hyodeoxycholic acid + NADP + Waterdetails
General function:
Involved in sequence-specific DNA binding transcription factor activity
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:
55913.9
General function:
Involved in binding
Specific function:
Ileal protein which stimulates gastric acid and pepsinogen secretion. Seems to be able to bind to bile salts and bilirubins. Isoform 2 is essential for the survival of colon cancer cells to bile acid-induced apoptosis
Gene Name:
FABP6
Uniprot ID:
P51161
Molecular weight:
14371.2
References
  1. Kurz M, Brachvogel V, Matter H, Stengelin S, Thuring H, Kramer W: Insights into the bile acid transportation system: the human ileal lipid-binding protein-cholyltaurine complex and its comparison with homologous structures. Proteins. 2003 Feb 1;50(2):312-28. [12486725 ]

Transporters

General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP)
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular weight:
77402.2
General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular weight:
76448.0
References
  1. Michalski C, Cui Y, Nies AT, Nuessler AK, Neuhaus P, Zanger UM, Klein K, Eichelbaum M, Keppler D, Konig J: A naturally occurring mutation in the SLC21A6 gene causing impaired membrane localization of the hepatocyte uptake transporter. J Biol Chem. 2002 Nov 8;277(45):43058-63. Epub 2002 Aug 23. [12196548 ]
General function:
Involved in ATP binding
Specific function:
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes
Gene Name:
ABCC3
Uniprot ID:
O15438
Molecular weight:
169341.1
General function:
Involved in ATP binding
Specific function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes
Gene Name:
ABCB11
Uniprot ID:
O95342
Molecular weight:
146405.8
General function:
Involved in bile acid:sodium symporter activity
Specific function:
Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism
Gene Name:
SLC10A2
Uniprot ID:
Q12908
Molecular weight:
37697.4
References
  1. Kramer W, Girbig F, Glombik H, Corsiero D, Stengelin S, Weyland C: Identification of a ligand-binding site in the Na+/bile acid cotransporting protein from rabbit ileum. J Biol Chem. 2001 Sep 21;276(38):36020-7. Epub 2001 Jul 10. [11447228 ]
General function:
Involved in bile acid:sodium symporter activity
Specific function:
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presence of sodium.
Gene Name:
SLC10A1
Uniprot ID:
Q14973
Molecular weight:
38118.64
General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids
Gene Name:
SLCO1A2
Uniprot ID:
P46721
Molecular weight:
74144.1
General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and of estrone-3-sulfate and taurocholate
Gene Name:
SLCO4A1
Uniprot ID:
Q96BD0
Molecular weight:
77192.5