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| Record Information |
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| Version | 4.0 |
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| Status | Detected and Quantified |
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| Creation Date | 2005-11-16 15:48:42 UTC |
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| Update Date | 2018-05-20 18:56:22 UTC |
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| HMDB ID | HMDB0000761 |
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| Secondary Accession Numbers | |
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| Metabolite Identification |
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| Common Name | Lithocholic acid |
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| Description | Lithocholic acid, also known as 3α-hydroxy-5β-cholan-24-oic acid or LCA, is a secondary bile acid. It is formed from chenodeoxycholate by bacterial action, and is 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. 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, lithocholic acid can act as an oncometabolite. An oncometabolite is a compound that when present at chronically high levels promotes tumour growth and survival. Chronically high levels of lithocholic acid are associated with several forms of cancer including colon cancer, pancreatic cancer, esophageal cancer, and many other GI cancers. 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 ). Dietary fibre can bind to lithocholic acid and aid in its excretion in stool. As such, fibre can protect against colon cancer. |
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| Structure | |
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| Synonyms | | Value | Source |
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| (3alpha,5beta)-3-Hydroxycholan-24-Oic acid | ChEBI | | 3alpha-Hydroxy-5beta-cholanate | ChEBI | | 3alpha-Hydroxy-5beta-cholanic acid | ChEBI | | 3alpha-Hydroxy-5beta-cholanoic acid | ChEBI | | 5beta-Cholanic acid-3alpha-ol | ChEBI | | (3a,5b)-3-Hydroxycholan-24-Oate | Generator | | (3a,5b)-3-Hydroxycholan-24-Oic acid | Generator | | (3alpha,5beta)-3-Hydroxycholan-24-Oate | Generator | | (3α,5β)-3-hydroxycholan-24-Oate | Generator | | (3α,5β)-3-hydroxycholan-24-Oic acid | Generator | | Lithocholate | Generator | | 3a-Hydroxy-5b-cholanate | Generator | | 3a-Hydroxy-5b-cholanic acid | Generator | | 3α-hydroxy-5β-cholanate | Generator | | 3α-hydroxy-5β-cholanic acid | Generator | | 3a-Hydroxy-5b-cholanoate | Generator | | 3a-Hydroxy-5b-cholanoic acid | Generator | | 3alpha-Hydroxy-5beta-cholanoate | Generator | | 3α-hydroxy-5β-cholanoate | Generator | | 3α-hydroxy-5β-cholanoic acid | Generator | | 5b-Cholanate-3a-ol | Generator | | 5b-Cholanic acid-3a-ol | Generator | | 5beta-Cholanate-3alpha-ol | Generator | | 5β-cholanate-3α-ol | Generator | | 5β-cholanic acid-3α-ol | Generator | | Acid, lithocholic | MeSH |
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| Chemical Formula | C24H40O3 |
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| Average Molecular Weight | 376.5726 |
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| Monoisotopic Molecular Weight | 376.297745146 |
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| IUPAC Name | (4R)-4-[(1S,2S,5R,7R,10R,11S,14R,15R)-5-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-yl]pentanoic acid |
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| Traditional Name | (4R)-4-[(1S,2S,5R,7R,10R,11S,14R,15R)-5-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-yl]pentanoic acid |
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| CAS Registry Number | 434-13-9 |
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| SMILES | [H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCC(O)=O |
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| 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 |
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| InChI Key | SMEROWZSTRWXGI-HVATVPOCSA-N |
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| Chemical Taxonomy |
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| Description | This compound belongs to the class of chemical entities known as monohydroxy bile acids, alcohols and derivatives. These are bile acids, alcohols or any of their derivatives bearing a hydroxyl group. |
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| Kingdom | Chemical entities |
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| Super Class | Organic compounds |
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| Class | Lipids and lipid-like molecules |
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| Sub Class | Steroids and steroid derivatives |
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| Direct Parent | Monohydroxy bile acids, alcohols and derivatives |
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| Alternative Parents | |
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| Substituents | - Monohydroxy bile acid, alcohol, or derivatives
- 3-hydroxysteroid
- Hydroxysteroid
- 3-alpha-hydroxysteroid
- Cyclic alcohol
- Secondary alcohol
- Carboxylic acid derivative
- Carboxylic acid
- Monocarboxylic acid or derivatives
- Organic oxide
- Alcohol
- Organic oxygen compound
- Carbonyl group
- Hydrocarbon derivative
- Organooxygen compound
- Aliphatic homopolycyclic compound
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| Molecular Framework | Aliphatic homopolycyclic compounds |
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| External Descriptors | |
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| Ontology |
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| Physiological effect | Health effect: |
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| Disposition | Route of exposure: Source: Biological location: |
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| Process | Naturally occurring process: |
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| Role | Industrial application: Biological role: |
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| Physical Properties |
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| State | Solid |
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| Experimental Properties | | Property | Value | Reference |
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| Melting Point | 186 °C | Not Available | | Boiling Point | Not Available | Not Available | | Water Solubility | 0.00038 mg/mL | Not Available | | LogP | Not Available | Not Available |
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| Predicted Properties | |
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| Spectra |
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| Spectra | |
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| Biological Properties |
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| Cellular Locations | |
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| Biospecimen Locations | |
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| Tissue Locations | |
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| Pathways | |
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| Normal Concentrations |
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| Bile | Detected and Quantified | 930 (890-960) uM | Adult (>18 years old) | Both | Normal | | details | | Blood | Detected and Quantified | 0.08 +/- 0.02 uM | Newborn (0-30 days old) | Both | Normal | | details | | Blood | Detected and Quantified | 0.33 +/-0.04 uM | Adult (>18 years old) | Both | Normal | | details | | Feces | Detected and Quantified | 1016.60 +/- 647.31 nmol/g dry feces | Not Specified | Not Specified | Normal | | details | | Feces | Detected but not Quantified | | Adult (>18 years old) | Both | Normal | | details | | Feces | Detected but not Quantified | | Adult (>18 years old) | Both | Normal | | details | | Urine | Detected and Quantified | 0.16 (0.10-0.20) umol/mmol creatinine | Adult (>18 years old) | Both | Normal | | details |
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| Abnormal Concentrations |
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| Blood | Detected and Quantified | 1.5 (0.5-3.0) uM | Adult (>18 years old) | Both | Biliary cirrhosis | | details | | Blood | Detected and Quantified | 0.11 +/- 0.04 uM | Newborn (0-30 days old) | Both | Extrahepatic biliary atresia (EHBA) | | details | | Blood | Detected and Quantified | 0.11 +/- 0.02 uM | Adult (>18 years old) | Both | Cystic fibrosis | | details | | Blood | Detected and Quantified | 0.16 +/- 0.07 uM | Children (1-13 years old) | Both | Cystic fibrosis | | details | | Feces | Detected but not Quantified | | Adult (>18 years old) | Both | Colorectal Cancer | | details | | Feces | Detected but not Quantified | | Adult (>18 years old) | Both | Colorectal Cancer | | details | | Feces | Detected but not Quantified | | Not Specified | Not Specified | Recurrent Clostridium difficile infection | | details | | Feces | Detected but not Quantified | | Adult (>18 years old) | Both | Colorectal cancer | | details | | Feces | Detected but not Quantified | | Adult (>18 years old) | Both | Clostridium difficile infection | | details | | Urine | Detected and Quantified | 0.32 (0.10-0.52) umol/mmol creatinine | Adult (>18 years old) | Both | Biliary cirrhosis | | details | | Urine | Detected and Quantified | 1.1 (0.41-2.4) umol/mmol creatinine | Adult (>18 years old) | Both | Biliary cirrhosis | | details |
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| Associated Disorders and Diseases |
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| Disease References | | Biliary atresia |
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- 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. [PubMed:16553252 ]
| | Colorectal cancer |
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- Sinha R, Ahn J, Sampson JN, Shi J, Yu G, Xiong X, Hayes RB, Goedert JJ: Fecal Microbiota, Fecal Metabolome, and Colorectal Cancer Interrelations. PLoS One. 2016 Mar 25;11(3):e0152126. doi: 10.1371/journal.pone.0152126. eCollection 2016. [PubMed:27015276 ]
- Brown DG, Rao S, Weir TL, O'Malia J, Bazan M, Brown RJ, Ryan EP: Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer Metab. 2016 Jun 6;4:11. doi: 10.1186/s40170-016-0151-y. eCollection 2016. [PubMed:27275383 ]
- Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]
| | Cystic fibrosis |
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- 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. [PubMed:15185309 ]
| | Primary biliary cirrhosis |
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- 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. [PubMed:2621422 ]
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| Associated OMIM IDs | |
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| External Links |
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| DrugBank ID | Not Available |
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| Phenol Explorer Compound ID | Not Available |
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| FoodDB ID | Not Available |
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| KNApSAcK ID | Not Available |
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| Chemspider ID | Not Available |
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| KEGG Compound ID | C03990 |
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| BioCyc ID | CPD-7235 |
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| BiGG ID | Not Available |
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| Wikipedia Link | Lithocholic_acid |
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| METLIN ID | Not Available |
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| PubChem Compound | 9903 |
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| PDB ID | Not Available |
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| ChEBI ID | 16325 |
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| References |
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| Synthesis Reference | Xu, 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. |
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| Material Safety Data Sheet (MSDS) | Not Available |
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| General References | - 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. [PubMed:16548228 ]
- 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. [PubMed:11344576 ]
- 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. [PubMed:417931 ]
- 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. [PubMed:6865641 ]
- Rudi J, Schonig T, Stremmel W: -Therapy with ursodeoxycholic acid in primary biliary cirrhosis in pregnancy-. Z Gastroenterol. 1996 Mar;34(3):188-91. [PubMed:8650973 ]
- 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. [PubMed:3349450 ]
- Greco AV, Mingrone G: Serum bile acid concentrations in mild liver cirrhosis. Clin Chim Acta. 1993 Nov 30;221(1-2):183-9. [PubMed:8149635 ]
- 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. [PubMed:15215624 ]
- 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. [PubMed:7372059 ]
- 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. [PubMed:8245717 ]
- 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. [PubMed:6777167 ]
- 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. [PubMed:7205448 ]
- 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. [PubMed:6800873 ]
- Hofmann AF: [Enterohepatic circulation of bile acids and biliary lipid secretion]. Minerva Med. 1977 Sep 19;68(43):3011-7. [PubMed:409965 ]
- Loof L, Wengle B: Enzymatic sulphation of bile salts in human liver. Biochim Biophys Acta. 1978 Sep 28;530(3):451-60. [PubMed:698243 ]
- 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. [PubMed:1850578 ]
- 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. [PubMed:2318979 ]
- 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. [PubMed:11316487 ]
- 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. [PubMed:16037564 ]
- 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. [PubMed:12576301 ]
- 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. [PubMed:11907135 ]
- Ajouz H, Mukherji D, Shamseddine A: Secondary bile acids: an underrecognized cause of colon cancer. World J Surg Oncol. 2014 May 24;12:164. doi: 10.1186/1477-7819-12-164. [PubMed:24884764 ]
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