MiMeDB: Showing metabocard for Lithocholic acid (MMDBc0000151)

Record Information

Version

1.0

Status

Detected and Quantified

Creation Date

2020-10-27 23:37:44 UTC

Update Date

2024-10-17 19:07:39 UTC

Metabolite ID

MMDBc0000151

Metabolite Identification

Common Name

Lithocholic acid

Description

Lithocholic acid, also known as 3Œ±-hydroxy-5Œ≤-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.

Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(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
Lithocholate	Kegg
(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
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	HMDB

Molecular Formula

C₂₄H₄₀O₃

Average Mass

376.5726

Monoisotopic Mass

376.297745146

IUPAC Name

Not Available

Traditional Name

Not Available

CAS Registry Number

434-13-9

SMILES

Not Available

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 Key

SMEROWZSTRWXGI-HVATVPOCSA-N

Chemical Taxonomy

Description

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.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Steroids and steroid derivatives

Sub Class

Bile acids, alcohols and derivatives

Direct Parent

Monohydroxy bile acids, alcohols and derivatives

Alternative Parents

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

Molecular Framework

Aliphatic homopolycyclic compounds

External Descriptors

bile acid (CHEBI:16325 )
monohydroxy-5beta-cholanic acid (CHEBI:16325 )
C24 bile acids, alcohols, and derivatives (C03990 )
Cholane and derivatives (C03990 )
C24 bile acids, alcohols, and derivatives (LMST04010003 )

Functional Ontology

Not Available

Physical Properties

State

Expected Solid

Predicted Properties

Not Available

Spectra

Not Available

Biological Properties

Cellular Locations

Extracellular

Biospecimen Locations

Bile
Blood
Feces
Intestine
Liver
Urine

Tissue Locations

Intestine
Liver

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0192053	Aldo-keto reductase family 1 member C1	Unknown	Q04828	Homo sapiens
MMDBp0192054	Aldo-keto reductase family 1 member C2	Unknown	P52895	Homo sapiens
MMDBp0192108	Solute carrier organic anion transporter family member 1B3	Transporter	Q9NPD5	Homo sapiens
MMDBp0192115	Solute carrier organic anion transporter family member 1B1	Transporter	Q9Y6L6	Homo sapiens
MMDBp0192630	Cytochrome P450 3A4	Unknown	P08684	Homo sapiens
MMDBp0193395	Canalicular multispecific organic anion transporter 2	Transporter	O15438	Homo sapiens
MMDBp0193400	Bile salt export pump	Transporter	O95342	Homo sapiens
MMDBp0193547	Ileal sodium/bile acid cotransporter	Transporter	Q12908	Homo sapiens
MMDBp0193558	Bile acid receptor	Enzyme	Q96RI1	Homo sapiens
MMDBp0193577	Sodium/bile acid cotransporter	Transporter	Q14973	Homo sapiens
MMDBp0193639	Solute carrier organic anion transporter family member 1A2	Transporter	P46721	Homo sapiens
MMDBp0193865	Solute carrier organic anion transporter family member 4A1	Transporter	Q96BD0	Homo sapiens
MMDBp0195864	Gastrotropin	Unknown	P51161	Homo sapiens

Human Pathways

Pathways

Name	SMPDB/PathBank

Metabolic Reactions

Reactions

Reaction ID	Precursor	Product	Enzyme	Data Source	Reference
MMDBr0004323	Lithocholic acid	Deoxycholic acid	Not Available	VMH	11980911
MMDBr0004324	Lithocholic acid	Deoxycholic acid	cytochrome P450, family 8, subfamily B, polypeptide 1	VMH	11980911
MMDBr0004325	Lithocholic acid	Lithocholyltaurine	bile acid CoA:amino acid N-acyltransferase	VMH	11980911
MMDBr0004326	Lithocholic acid	Lithocholyltaurine	bile acid CoA:amino acid N-acyltransferase	VMH	11980911
MMDBr0004327	Glycine	Lithocholic acid glycine conjugate	bile acid CoA:amino acid N-acyltransferase	VMH	11980911
MMDBr0004328	Glycine	Lithocholic acid glycine conjugate	bile acid CoA:amino acid N-acyltransferase	VMH	11980911
MMDBr0006130	3Beta-Hydroxy-5-Cholestenal	Lithocholic acid	Not Available	VMH	30371894
MMDBr0009602	Lithocholic acid	Hyodeoxycholic acid	cytochrome P450, family 3, subfamily A, polypeptide 4	VMH; KEGG	30371894

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference
Biliary atresia	Slight Increase	Association	Human Blood	HMDB	16553252
Cystic fibrosis	Decreased	Association	Human Blood	HMDB	15185309
Primary biliary cirrhosis	Slight Increase	Association	Human Urine	HMDB	2621422
Primary biliary cirrhosis	Increased	Association	Human Blood	HMDB	2621422

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Bacteria	Firmicutes	16	Human ; Human feces; Human saliva; Human mucosa; Human stool	Microbial culture; Indirect association between microbiota composition and metabolites measured in host biospecimen; Metabolic reconstruction
Bacteria	Bacteroidetes	2	Human feces; Human ; Human urine; Human stool; Human saliva	Microbial culture
Bacteria	Actinobacteria	7	Human ; Human feces; Human saliva; Human mucosa; Human sputum; Human supragingival plaque; Human subgingival plaque	Microbial culture; Indirect association between microbiota composition and metabolites measured in host biospecimen; Metabolic reconstruction

Exposure Sources

Source Type	Activity	Data Source	Reference
Cosmetics	Not Available	U.S. Environmental Protection Agency	CompTox
Domestics	Not Available	U.S. Environmental Protection Agency	CompTox
Domestics	Not Available	U.S. Environmental Protection Agency	CompTox

Host Biospecimen and Location

Host and Biospecimen	Status	Mean	Std	Min	Max	Units	Age	Sex	Health Condition	Data Source	Reference
Human Feces	Detected but not Quantified									HMDB
Human Blood	Detected and Quantified	0.11	0.04			uM	Newborn (0-30 days old)	Both	Extrahepatic biliary atresia (EHBA)	HMDB	16553252
Human Blood	Detected and Quantified	0.11	0.02			uM	Adult (>18 years old)	Both	Cystic fibrosis	HMDB	15185309
Human Blood	Detected and Quantified	0.16	0.07			uM	Children (1-13 years old)	Both	Cystic fibrosis	HMDB	15185309
Human Urine	Detected and Quantified	0.32		0.10	0.52	umol/mmol creatinine	Adult (>18 years old)	Both	Biliary cirrhosis	HMDB	2621422
Human Urine	Detected and Quantified	1.1		0.41	2.4	umol/mmol creatinine	Adult (>18 years old)	Both	Biliary cirrhosis	HMDB	2621422
Human Blood	Detected and Quantified	1.5		0.5	3.0	uM	Adult (>18 years old)	Both	Biliary cirrhosis	HMDB	2621422
Human Blood	Detected and Quantified	0.08	0.02			uM	Newborn (0-30 days old)	Both	Normal	HMDB	16553252
Human Urine	Detected and Quantified	0.16		0.10	0.20	umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	24023812
Human Blood	Detected and Quantified	0.33	0.04			uM	Adult (>18 years old)	Both	Normal	HMDB	15185309
Human Feces	Detected and Quantified	1016.60	647.31			nmol/g dry feces	Not Specified	Not Specified	Normal	HMDB	22664055
Human Bile	Detected and Quantified	930		890	960	uM	Adult (>18 years old)	Both	Normal	HMDB	16548228
Human Intestine	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Liver	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	27543620
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	25037050
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	29808030
Human Urine	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057
Human Blood	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057

External Links

HMDB ID

HMDB0000761

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

KNApSAcK ID

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Not Available

Wikipedia Link

Lithocholic_acid

METLIN ID

209

PubChem Compound

9903

PDB ID

Not Available

ChEBI ID

16325

Food Biomarker Ontology

Not Available

References

Synthesis Reference

Not Available

General References

Hofmann AF: [Enterohepatic circulation of bile acids and biliary lipid secretion]. Minerva Med. 1977 Sep 19;68(43):3011-7. [PubMed:409965 ]
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. doi: 10.1111/j.1365-2362.1978.tb00807.x. [PubMed:417931 ]
Loof L, Wengle B: Enzymatic sulphation of bile salts in human liver. Biochim Biophys Acta. 1978 Sep 28;530(3):451-60. doi: 10.1016/0005-2760(78)90165-0. [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. doi: 10.1093/ajcn/53.5.1259. [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. doi: 10.1172/JCI114561. [PubMed:2318979 ]
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. doi: 10.1016/0304-3835(88)90023-7. [PubMed:3349450 ]
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. doi: 10.1111/j.1365-2362.1980.tb00044.x. [PubMed:6777167 ]
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 ]
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. doi: 10.1016/0024-3205(83)90643-4. [PubMed:6865641 ]
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. doi: 10.1016/s0022-3476(81)80702-0. [PubMed:7205448 ]
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 ]
Greco AV, Mingrone G: Serum bile acid concentrations in mild liver cirrhosis. Clin Chim Acta. 1993 Nov 30;221(1-2):183-9. doi: 10.1016/0009-8981(93)90032-y. [PubMed:8149635 ]
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 ]
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 ]
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. doi: 10.1242/jeb.204.10.1673. [PubMed:11316487 ]
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. doi: 10.1172/JCI107596. [PubMed:11344576 ]
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 ]
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. doi: 10.1152/ajpgi.00417.2002. [PubMed:12576301 ]
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. doi: 10.1111/j.1348-0421.2004.tb03526.x. [PubMed:15215624 ]
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. doi: 10.1161/01.ATV.0000178994.21828.a7. Epub 2005 Jul 21. [PubMed:16037564 ]
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 ]
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 ]

Showing metabocard for Lithocholic acid (MMDBc0000151)

MOL for #<Metabolite:0x00007fdb0ff92eb8>

3D MOL for #<Metabolite:0x00007fdb0ff92eb8>

3D SDF for #<Metabolite:0x00007fdb0ff92eb8>

3D-SDF for #<Metabolite:0x00007fdb0ff92eb8>

PDB for #<Metabolite:0x00007fdb0ff92eb8>

3D PDB for #<Metabolite:0x00007fdb0ff92eb8>

SMILES for #<Metabolite:0x00007fdb0ff92eb8>

INCHI for #<Metabolite:0x00007fdb0ff92eb8>

Structure for #<Metabolite:0x00007fdb0ff92eb8>

3D Structure for #<Metabolite:0x00007fdb0ff92eb8>