Disorders of bile acid synthesis and biliary transport (Homo sapiens)

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CYTOSOLSLCO1B1SLCO1B31, 16, 3126 PEROXISOMEProteinMore significant in adults.CatalysisPORTAL BLOOD SYSTEM- Side-chain shortening through β-oxidation - Converting C27-bile acids (cholestanoids) to C24-bile acids (cholanoids). - Amidation of newly synthesized bile acidsGeneProductInvolved enzymes(different cellular locations)- Amidation of recycled bile acidsConversionTransporters:Bile acid-CoAligase deficiencyMetaboliteConnection to diseaseAssummed to be spontenous conversions (pH difference)CANALICULUSHEPATOCYTE'Acidic' pathway5beta-cholestane-3alpha,7alpha,26-triolSCPxBACSCBH3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl-CoA(24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy-5beta-cholestan-26-oyl-CoA3alpha,7alpha,24-trihydroxy-5beta-cholestan-26-oyl-CoA(25S)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oic acidACOX23α,7α,12α-trihydroxy-24-oxo-5β-cholestan-26-oyl-CoABilirubin disposal3alpha,7alpha-Dihydroxy-5beta-cholest-24-enoyl-CoAtaurocholateglycocholateTaurine3alpha,7alpha,12alpha-Trihydroxy-5beta-cholest-24-enoyl-CoA3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid3alpha,7alpha-dihydroxy-5beta-cholestan-26-al6, 255beta-cholestane-3alpha,7alpha,12alpha,26-tetrol7alpha,26-dihydroxycholest-4-en-3-one7alpha,26-dihydroxy-5beta-cholestan-3-onePhosphatidylserine3beta-Hydroxy-5-cholestenoic acidABCB11Bile acidABCC2phosphatidylcholinesBilirubin glucuronidechenodeoxycholate(1-)SLC27A5cholesterol7-alpha-HydroxycholesterolCYP7A17alpha,12alpha-Dihydroxy-4-cholesten-3-one(25S)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoA5beta-cholestane-3alpha,7alpha,12alpha-triolGlycocholic acidABCB4CYP7B1HSD3B7(25R)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoAcholyl-CoA3beta,7alpha-Dihydroxy-5-cholestenoateTaurocholic acidChenodeoxycholoyl-CoA7alpha,12alpha-dihydroxy-5beta-cholestan-3-one5beta-cholestane-3alpha,7alpha-diolcholate27-Hydroxycholesterol7alpha-hydroxy-5beta-cholestan-3-oneAKR1D17alpha-Hydroxy-4-cholesten-3-oneGlycochenodeoxycholic acidCYP8B1Taurochenodeoxycholic acid5beta-Cholestane-3alpha,7alpha,27-triol'Neutral' pathwayAMACRHSD3B7Aldo-keto reductase family 1 member C4HEPATOCYTEATP8B1CYP27A1AKR1D1CYP27A13β-Dehydrogenase deficiency4, 7, 125β-Reductase deficiency7, 10, 17Spastic Paraplegia 5A2, 8Cholesterol 7α-hydroxylase deficiency11Sterol 27-hydroxylase deficiency19, 30Bile acid amidation defect24Bile acid amidation defect24Bile acid-CoA ligase deficiency21Bilirubin glucuronidephosphatidylcholinesPhosphatidylserineBile acidABCC2 deficiency18ABCB4 deficiency20ATP8B1 deficiency15ABCB11 deficiency15OATP1B1 disease283β-Dehydrogenase deficiency4, 7, 125β-Reductase deficiency7, 10, 17AMACR deficiency9, 13, 27OATP1B3 disease28cholesterolSterol 27-hydroxylase deficiency19, 30HSD17B4Aldo-keto reductase family 1 member C4CYP27A1Very long-chain acyl-CoA synthetaseglycocholatetaurocholateSterol carrier protein 2 deficiency 23Congenital bile acid synthesis defect 63, 5D-bifunctional protein deficiency14, 22, 29LegendDiseaseMore prominant early in life.ENDOPLASMATIC RETICULUM (25R)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoA(25R)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestan-26-oyl-CoA(25R)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestan-26-oyl-CoAABCD3 or PMP70Congenital bileacid synthesisdefect type 5Bile acid-CoA:amino acid N-acyltransferaseBile acid-CoA:amino acid N-acyltransferase1Enterohepatic circulation of bile acidsNTCPOATP1B1OATP1B3MRP2MRP3BSEPMRP4OSTαOSTβMDR1ILBPASBT


Description

This pathway model displays disorders of bile acid synthesis and biliary transport.

Bile acids have a crucial role in the absorption of lipids and hydrophilic vitamins. Furthermore, bile acids aid in the maintenance of cholesterol homeostasis, excretion of toxic substances, processing of food intake, and used as signaling molecules influencing glucose homeostasis, lipid metabolism, and energy expenditure. First, bile acids with a low solubility (less hydrophilic, unconjugated) must be activated using CoA, so that conjugation to taurine or glycine can happen.

This model includes 20 disorders, of which 14 are enzyme deficiencies, and 6 are related to transporters.

The enzyme deficiencies include 3β-Dehydrogenase deficiency, 5β-Reductase deficiency, Spastic Paraplegia 5A, Cholesterol 7α-hydroxylase deficiency, Sterol 27-hydroxylase deficiency, α-Methylacyl-CoA racemase (AMACR) deficiency, Bile acid amidation defect, and Bile acid-CoA ligase deficiency (BA CoA LD, BACS), congenital bile acid synthesis defect 6 and type 5, D-bifunctional protein deficiency, sterol carrier protein 2 deficiency.

Disorders of transporters are related to deficiencies in ATP8B1 (Progressive familial intrahepatic cholestasis type 1; PFIC1), ABCB11 (Progressive familial intrahepatic cholestasis type 2; PFIC 2), ABCB4 (Progressive familial intrahepatic cholestasis type 3), and ABCC2 (Dubin-Johnson syndrome), as well as Rotor Syndrome (linked to two distinct genes, OATP1B1 and OATP1B3, related to taurocholate and glycocholate transport).


This pathway is based on Chapter 34 of Blau’s ‘Physicians Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases (ISBN 3642403360 (978-3642403361)), edition 4 (and is currently in the process of being updated to edition 5, Chapter 56). We would like to thank two authors from this chapter (Frédéric M. Vaz and Sacha Ferdinandusse) for their efforts in curating this pathway model!

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Bibliography

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  1. Frédéric M Vaz, Sacha Ferdinandusse; ''Bile acid analysis in human disorders of bile acid biosynthesis''; Mol. Aspects Med., 2017 PubMed Europe PMC Scholia
  2. Setchell KD, Schwarz M, O'Connell NC, Lund EG, Davis DL, Lathe R, Thompson HR, Weslie Tyson R, Sokol RJ, Russell DW; ''Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease.''; J Clin Invest, 1998 PubMed Europe PMC Scholia
  3. Vilarinho S, Sari S, Mazzacuva F, Bilgüvar K, Esendagli-Yilmaz G, Jain D, Akyol G, Dalgiç B, Günel M, Clayton PT, Lifton RP; ''ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment.''; Proc Natl Acad Sci U S A, 2016 PubMed Europe PMC Scholia
  4. Subramaniam P, Clayton PT, Portmann BC, Mieli-Vergani G, Hadzić N; ''Variable clinical spectrum of the most common inborn error of bile acid metabolism--3beta-hydroxy-Delta 5-C27-steroid dehydrogenase deficiency.''; J Pediatr Gastroenterol Nutr, 2010 PubMed Europe PMC Scholia
  5. Monte MJ, Alonso-Peña M, Briz O, Herraez E, Berasain C, Argemi J, Prieto J, Marin JJG; ''ACOX2 deficiency: An inborn error of bile acid synthesis identified in an adolescent with persistent hypertransaminasemia.''; J Hepatol, 2017 PubMed Europe PMC Scholia
  6. Sean E McGarr, Jason M Ridlon, Phillip B Hylemon; ''Diet, anaerobic bacterial metabolism, and colon cancer: a review of the literature''; J. Clin. Gastroenterol., 2005 PubMed Europe PMC Scholia
  7. Clayton PT; ''Disorders of bile acid synthesis.''; J Inherit Metab Dis, 2011 PubMed Europe PMC Scholia
  8. Arnoldi A, Crimella C, Tenderini E, Martinuzzi A, D'Angelo MG, Musumeci O, Toscano A, Scarlato M, Fantin M, Bresolin N, Bassi MT; ''Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations.''; Clin Genet, 2012 PubMed Europe PMC Scholia
  9. Setchell KD, Heubi JE, Bove KE, O'Connell NC, Brewsaugh T, Steinberg SJ, Moser A, Squires RH Jr; ''Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy.''; Gastroenterology, 2003 PubMed Europe PMC Scholia
  10. Lemonde HA, Custard EJ, Bouquet J, Duran M, Overmars H, Scambler PJ, Clayton PT; ''Mutations in SRD5B1 (AKR1D1), the gene encoding delta(4)-3-oxosteroid 5beta-reductase, in hepatitis and liver failure in infancy.''; Gut, 2003 PubMed Europe PMC Scholia
  11. Pullinger CR, Eng C, Salen G, Shefer S, Batta AK, Erickson SK, Verhagen A, Rivera CR, Mulvihill SJ, Malloy MJ, Kane JP; ''Human cholesterol 7alpha-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype.''; J Clin Invest, 2002 PubMed Europe PMC Scholia
  12. Clayton PT, Leonard JV, Lawson AM, Setchell KD, Andersson S, Egestad B, Sjövall J; ''Familial giant cell hepatitis associated with synthesis of 3 beta, 7 alpha-dihydroxy-and 3 beta,7 alpha, 12 alpha-trihydroxy-5-cholenoic acids.''; J Clin Invest, 1987 PubMed Europe PMC Scholia
  13. Ferdinandusse S, Denis S, Clayton PT, Graham A, Rees JE, Allen JT, McLean BN, Brown AY, Vreken P, Waterham HR, Wanders RJ; ''Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy.''; Nat Genet, 2000 PubMed Europe PMC Scholia
  14. Gloerich J, Denis S, van Grunsven EG, Dacremont G, Wanders RJ, Ferdinandusse S; ''A novel HPLC-based method to diagnose peroxisomal D-bifunctional protein enoyl-CoA hydratase deficiency.''; J Lipid Res, 2003 PubMed Europe PMC Scholia
  15. Pawlikowska L, Strautnieks S, Jankowska I, Czubkowski P, Emerick K, Antoniou A, Wanty C, Fischler B, Jacquemin E, Wali S, Blanchard S, Nielsen IM, Bourke B, McQuaid S, Lacaille F, Byrne JA, van Eerde AM, Kolho KL, Klomp L, Houwen R, Bacchetti P, Lobritto S, Hupertz V, McClean P, Mieli-Vergani G, Shneider B, Nemeth A, Sokal E, Freimer NB, Knisely AS, Rosenthal P, Whitington PF, Pawlowska J, Thompson RJ, Bull LN; ''Differences in presentation and progression between severe FIC1 and BSEP deficiencies.''; J Hepatol, 2010 PubMed Europe PMC Scholia
  16. Nenad Blau, Marinus Duran, K Michael Gibson, Carlo Dionisi Vici; ''Physicians Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases''; Springer, 2014
  17. Clayton PT; ''Delta 4-3-oxosteroid 5 beta-reductase deficiency and neonatal hemochromatosis.''; J Pediatr, 1994 PubMed Europe PMC Scholia
  18. Talaga ZJ, Vaidya PN; ''Dubin Johnson Syndrome''; , 2022 PubMed Europe PMC Scholia
  19. Verrips A, Hoefsloot LH, Steenbergen GC, Theelen JP, Wevers RA, Gabreëls FJ, van Engelen BG, van den Heuvel LP; ''Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis.''; Brain, 2000 PubMed Europe PMC Scholia
  20. Jones-Hughes T, Campbell J, Crathorne L; ''Epidemiology and burden of progressive familial intrahepatic cholestasis: a systematic review.''; Orphanet J Rare Dis, 2021 PubMed Europe PMC Scholia
  21. Chong CP, Mills PB, McClean P, Gissen P, Bruce C, Stahlschmidt J, Knisely AS, Clayton PT; ''Bile acid-CoA ligase deficiency--a new inborn error of bile acid metabolism.''; J Inherit Metab Dis, 2012 PubMed Europe PMC Scholia
  22. Grønborg S, Krätzner R, Spiegler J, Ferdinandusse S, Wanders RJ, Waterham HR, Gärtner J; ''Typical cMRI pattern as diagnostic clue for D-bifunctional protein deficiency without apparent biochemical abnormalities in plasma.''; Am J Med Genet A, 2010 PubMed Europe PMC Scholia
  23. Ferdinandusse S, Kostopoulos P, Denis S, Rusch H, Overmars H, Dillmann U, Reith W, Haas D, Wanders RJ, Duran M, Marziniak M; ''Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy.''; Am J Hum Genet, 2006 PubMed Europe PMC Scholia
  24. Hadžić N, Bull LN, Clayton PT, Knisely AS; ''Diagnosis in bile acid-CoA: amino acid N-acyltransferase deficiency.''; World J Gastroenterol, 2012 PubMed Europe PMC Scholia
  25. Zixing Dong, Byong H. Lee; ''Bile salt hydrolases: Structure and function, substrate preference, and inhibitor development''; Protein Sci., 2018 PubMed Europe PMC Scholia
  26. Stephanie J Mihalik, Steven J Steinberg, Zhengtong Pei, Joseph Park, Do G Kim, Ann K Heinzer, Georges Dacremont, Ronald J A Wanders, Dean A Cuebas, Kirby D Smith, Paul A Watkins; ''Participation of two members of the very long-chain acyl-CoA synthetase family in bile acid synthesis and recycling''; J. Biol. Chem., 2002 PubMed Europe PMC Scholia
  27. Thompson SA, Calvin J, Hogg S, Ferdinandusse S, Wanders RJ, Barker RA; ''Relapsing encephalopathy in a patient with alpha-methylacyl-CoA racemase deficiency.''; J Neurol Neurosurg Psychiatry, 2008 PubMed Europe PMC Scholia
  28. van de Steeg E, Stránecký V, Hartmannová H, Nosková L, Hřebíček M, Wagenaar E, van Esch A, de Waart DR, Oude Elferink RP, Kenworthy KE, Sticová E, al-Edreesi M, Knisely AS, Kmoch S, Jirsa M, Schinkel AH; ''Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver.''; J Clin Invest, 2012 PubMed Europe PMC Scholia
  29. McMillan HJ, Worthylake T, Schwartzentruber J, Gottlieb CC, Lawrence SE, Mackenzie A, Beaulieu CL, Mooyer PA, Wanders RJ, Majewski J, Bulman DE, Geraghty MT, Ferdinandusse S, Boycott KM; ''Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency.''; Orphanet J Rare Dis, 2012 PubMed Europe PMC Scholia
  30. Clayton PT, Verrips A, Sistermans E, Mann A, Mieli-Vergani G, Wevers R; ''Mutations in the sterol 27-hydroxylase gene (CYP27A) cause hepatitis of infancy as well as cerebrotendinous xanthomatosis.''; J Inherit Metab Dis, 2002 PubMed Europe PMC Scholia
  31. Nenad Blau, Carlo Dionisi Vici, Carlos R. Ferreira, Christine Vianey-Saban, Clara D. M. van Karnebeek; ''Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases''; Springer, 2021

History

View all...
CompareRevisionActionTimeUserComment
128232view13:42, 29 January 2024EweitzSoften disease color
126993view15:09, 12 July 2023DeSlAdded detail for taurocholic acid conversion
126987view14:34, 12 July 2023DeSlAdded enzyme nodes for enterohepatic circulation
126952view13:38, 7 July 2023DeSlOntology Term : 'transport pathway' added !
126951view13:38, 7 July 2023DeSlOntology Term : 'secondary bile acid biosynthetic pathway' added !
126950view13:38, 7 July 2023DeSlOntology Term : 'primary bile acid biosynthetic pathway' added !
126948view13:37, 7 July 2023DeSlAdded link to WP5396
126946view13:17, 7 July 2023DeSlAdded another pathway for referal
126944view13:05, 7 July 2023DeSlUpdated layout
126943view13:04, 7 July 2023DeSlAdded three primary references describing the pathway
126942view13:00, 7 July 2023DeSlAdded dual localization of BAAT and ref.
126940view12:31, 7 July 2023DeSlAdded transport to PR for THC-CoA by ABCD3, added new disorder to description
126939view12:02, 7 July 2023DeSlTrying to resolve issues between ID mapping for taurocholate and taurocholic acid; added bacterial conversion CB(A)H
126938view11:32, 7 July 2023DeSlAdded BACS in ER
126937view11:24, 7 July 2023DeSlAdded link to other relevant PW from Blau book (ch. 58, ed. 5)
126936view11:20, 7 July 2023DeSlUnified OMIM IDs, updated description with more disorder names
126935view11:10, 7 July 2023DeSlAdded BACS related IMD
126934view10:08, 7 July 2023DeSlMerging identifical disease nodes, reconnected some proteins to one datanode
126933view09:57, 7 July 2023DeSlUpdated description
126932view09:36, 7 July 2023DeSlAdded BACS protein in pathway model
123799view12:29, 15 August 2022EgonwI am guess it is not specifically the sodium salt
122283view13:54, 17 March 2022DeSlmore layout changes for PW condensation
122282view13:45, 17 March 2022DeSlAdditional condensation of pathways
122280view13:38, 17 March 2022DeSlStarted condensing pathway and structuring layout.
122276view11:49, 17 March 2022DeSlChanged layout for some disorder nodes
122265view16:43, 16 March 2022Maria van de MeentReplaced a non-existant Rhea identifier with an existing identifier.
122009view09:41, 9 March 2022Maria van de MeentAnother attempt to fix glycocholate interactions.
122006view09:34, 9 March 2022Maria van de MeentUsed type converter plugin to fix legend interactions.
121898view00:20, 8 March 2022Maria van de MeentOntology Term : 'congenital bile acid synthesis defect' added !
121897view00:16, 8 March 2022Maria van de MeentOntology Term : 'alpha-methylacyl-CoA racemase deficiency' added !
121896view00:14, 8 March 2022Maria van de MeentOntology Term : 'Dubin-Johnson syndrome' added !
121895view00:14, 8 March 2022Maria van de MeentOntology Term : 'progressive familial intrahepatic cholestasis 3' added !
121894view00:14, 8 March 2022Maria van de MeentOntology Term : 'progressive familial intrahepatic cholestasis 2' added !
121893view00:13, 8 March 2022Maria van de MeentOntology Term : 'progressive familial intrahepatic cholestasis 1' added !
121892view00:11, 8 March 2022Maria van de MeentOntology Term : 'cerebrotendinous xanthomatosis' added !
121891view00:11, 8 March 2022Maria van de MeentOntology Term : 'hereditary spastic paraplegia 5A' added !
121890view00:09, 8 March 2022Maria van de MeentOntology Term : 'bile acid transport pathway' added !
121889view00:08, 8 March 2022Maria van de MeentOntology Term : 'bile acid biosynthetic pathway' added !
121888view00:02, 8 March 2022Maria van de MeentOntology Term : 'PW:0001475' removed !
121887view00:01, 8 March 2022Maria van de MeentOntology Term : 'disease pathway' added !
121886view00:00, 8 March 2022Maria van de MeentOntology Term : 'hepatocyte' added !
121885view23:54, 7 March 2022Maria van de MeentAdded a legend.
121880view23:27, 7 March 2022Maria van de MeentSecond attempt to fix an interaction.
121879view23:24, 7 March 2022Maria van de MeentReviewed outdated database identifiers, fixed two incomplete interactions, added additional diseases and their OMIM identifiers.
121648view11:15, 23 February 2022Maria van de MeentChanged colour of disease nodes and pathway labels, added alternative names to some metabolites, and organized the pathway a bit more.
121527view08:15, 21 February 2022Maria van de MeentOntology Term : 'inborn error of metabolism pathway' added !
121526view08:14, 21 February 2022Maria van de MeentOntology Term : 'cerebrotendinous xanthomatosis pathway' added !
121513view12:57, 20 February 2022Maria van de MeentFixed lines that were not properly connected.
121499view13:06, 18 February 2022Maria van de MeentHepatocyte layout change.
121498view13:03, 18 February 2022Maria van de MeentAdded some additional comments to disease nodes and made small changes to pathway layout.

External references

DataNodes

View all...
NameTypeDatabase referenceComment
(24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy -5beta-cholestan-26-oyl-CoAMetaboliteCHEBI:52050 (ChEBI)
(25R)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestan-26-oyl-CoAMetaboliteCHEBI:37642 (ChEBI) AKA THC-CoA
(25R)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoAMetaboliteHMDB0060304 (HMDB)
(25S)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoAMetaboliteCHEBI:37643 (ChEBI)
(25S)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoAMetaboliteHMDB0060306 (HMDB)
27-HydroxycholesterolMetaboliteCHEBI:17703 (ChEBI) C27-carboxylic acid
3alpha,7alpha,12alpha-Trihydroxy-5beta-cholest-24-enoyl-CoAMetaboliteCHEBI:27505 (ChEBI)
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-alMetaboliteCHEBI:16466 (ChEBI)
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oic acidMetaboliteCHEBI:18402 (ChEBI) AKA THCA, trihydroxycholestanoic acid, 3α,7α,12α-trihydroxy-5β-cholestanoic acid
3alpha,7alpha,24-trihydroxy -5beta-cholestan-26-oyl-CoAMetaboliteQ27103111 (Wikidata)
3alpha,7alpha-Dihydroxy-5beta-cholest-24-enoyl-CoAMetaboliteCHEBI:27393 (ChEBI)
3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl-CoAMetaboliteCHEBI:87704 (ChEBI)
3alpha,7alpha-dihydroxy-5beta-cholestan-26-alMetaboliteCHEBI:27428 (ChEBI)
3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acidMetaboliteCHEBI:16577 (ChEBI)
3beta,7alpha-Dihydroxy-5-cholestenoateMetaboliteHMDB0012454 (HMDB) Alternative name: 3β,7α-Dihydroxy-5-cholestenoic acid
3beta-Hydroxy-5-cholestenoic acidMetaboliteCHEBI:81014 (ChEBI)
3α,7α,12α-trihydroxy-24-oxo-5β-cholestan-26-oyl-CoAMetaboliteCHEBI:27379 (ChEBI)
5beta-Cholestane-3alpha,7alpha,27-triolMetaboliteHMDB0060138 (HMDB) Alternative name: 5β-Cholestan-3α,7α,27-triol
5beta-cholestane-3alpha,7alpha,12alpha,26-tetrolMetaboliteCHEBI:17278 (ChEBI)
5beta-cholestane-3alpha,7alpha,12alpha-triolMetaboliteCHEBI:16496 (ChEBI)
5beta-cholestane-3alpha,7alpha,26-triolMetaboliteCHEBI:28540 (ChEBI)
5beta-cholestane-3alpha,7alpha-diolMetaboliteCHEBI:28047 (ChEBI)
7-alpha-HydroxycholesterolMetaboliteCHEBI:17500 (ChEBI)
7alpha,12alpha-Dihydroxy-4-cholesten-3-oneMetaboliteCHEBI:28477 (ChEBI)
7alpha,12alpha-dihydroxy-5beta-cholestan-3-oneMetaboliteCHEBI:2288 (ChEBI)
7alpha,26-dihydroxy-5beta-cholestan-3-oneMetaboliteCHEBI:48778 (ChEBI)
7alpha,26-dihydroxycholest-4-en-3-oneMetaboliteCHEBI:48825 (ChEBI)
7alpha-Hydroxy-4-cholesten-3-oneMetaboliteCHEBI:17899 (ChEBI)
7alpha-hydroxy-5beta-cholestan-3-oneMetaboliteCHEBI:2290 (ChEBI)
ABCB11GeneProductENSG00000073734 (Ensembl)
ABCB4GeneProductENSG00000005471 (Ensembl)
ABCC2GeneProductENSG00000023839 (Ensembl)
ABCD3 or PMP70ProteinP28288 (Uniprot-TrEMBL)
ACOX2GeneProductENSG00000168306 (Ensembl)
AKR1D1GeneProductENSG00000122787 (Ensembl)
AMACRGeneProductQ9UHK6 (Uniprot-TrEMBL)
ASBTProteinQ12908 (Uniprot-TrEMBL) AKA SLC10A2
ATP8B1GeneProductENSG00000081923 (Ensembl)
Aldo-keto reductase family 1 member C4ProteinP17516 (Uniprot-TrEMBL)
BACSProteinQ9Y2P5 (Uniprot-TrEMBL) AKA Bile acid-CoA ligase, gene symbol: SLC27A5, Long-chain fatty acid transport protein 5
BSEPProteinO95342 (Uniprot-TrEMBL) AKA ABCB11
Bile acid-CoA:amino acid N-acyltransferaseProteinQ14032 (Uniprot-TrEMBL) amino acid N-acyltransferase (BAAT), which has a dual localization (peroxisome and cytosol)
Bile acidMetaboliteCHEBI:36277 (ChEBI)
Bilirubin disposalPathway
Bilirubin glucuronideMetaboliteCHEBI:16427 (ChEBI)
CBHProteinP54965 (Uniprot-TrEMBL)
  • AKA conjugated bile acid hydrolase, or CBAH, bacterial conversion
  • Tentatively annotated for species Clostridium perfringens (strain 13 / Type A), C. perfringens, based on Table 1 from PMID: 30098054
CYP27A1GeneProductENSG00000135929 (Ensembl)
CYP7A1GeneProductENSG00000167910 (Ensembl) aka sterol 7α-hydroxylase
CYP7B1GeneProductENSG00000172817 (Ensembl)
CYP8B1GeneProductQ9UNU6 (Uniprot-TrEMBL)
Chenodeoxycholoyl-CoAMetaboliteCHEBI:28701 (ChEBI)
Enterohepatic circulation of bile acidsPathwayWP5396 (WikiPathways)
Glycochenodeoxycholic acidMetaboliteCHEBI:36274 (ChEBI)
Glycocholic acidMetaboliteCHEBI:17687 (ChEBI)
HSD17B4GeneProductENSG00000133835 (Ensembl)
HSD3B7GeneProductENSG00000099377 (Ensembl)
ILBPProteinP51161 (Uniprot-TrEMBL) AKA FABP6
MDR1ProteinP08183 (Uniprot-TrEMBL) AKA ABCB1A (PMID:21103970), UniProt: ABCB1 (ABCB1A is used for mouse). MDR1A in Figure (PMID:21103970)
MRP2ProteinQ92887 (Uniprot-TrEMBL) AKA ABCC2
MRP3ProteinO15438 (Uniprot-TrEMBL) AKA ABCC3
MRP4ProteinO15439 (Uniprot-TrEMBL) AKA ABBC4 (PMID:21103970); according to UniProt ABCC4 is the correct gene name.
NTCPProteinQ14973 (Uniprot-TrEMBL) AKA SLC10A1
OATP1B1ProteinQ9Y6L6 (Uniprot-TrEMBL) AKA SLCO1B1
OATP1B3ProteinQ9NPD5 (Uniprot-TrEMBL) AKA SLCO1B3
OSTαProteinQ86UW1 (Uniprot-TrEMBL) heteromeric transporter OSTα-OSTβ , assumed to be gene SLC51A based on UniProt entry (gene name not mentioned in publication)
OSTβProteinQ86UW2 (Uniprot-TrEMBL) heteromeric transporter OSTα-OSTβ , assumed to be gene SLC51B based on UniProt entry (gene name not mentioned in publication)
PhosphatidylserineMetaboliteCHEBI:18303 (ChEBI)
SCPxGeneProductP22307 (Uniprot-TrEMBL) Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoA [Source: UniProt]
SLC27A5GeneProductENSG00000083807 (Ensembl)
SLCO1B1GeneProductQ9Y6L6 (Uniprot-TrEMBL)
SLCO1B3GeneProductQ9NPD5 (Uniprot-TrEMBL)
TaurineMetaboliteCHEBI:507393 (ChEBI)
Taurochenodeoxycholic acidMetaboliteCHEBI:16525 (ChEBI)
Taurocholic acidMetaboliteCHEBI:36257 (ChEBI)
Very long-chain acyl-CoA synthetaseProteinO14975 (Uniprot-TrEMBL)
  • Full name: very long chain acyl-CoA synthase (VLCS)/di-/trihydroxycholestanoic acid-CoA ligase
  • Check annotation of this enzyme!
chenodeoxycholate(1-)MetaboliteCHEBI:36234 (ChEBI)
cholateMetaboliteCHEBI:29747 (ChEBI)
cholesterolMetaboliteCHEBI:16113 (ChEBI)
cholyl-CoAMetaboliteCHEBI:15519 (ChEBI)
glycocholateMetaboliteCHEBI:29746 (ChEBI)
phosphatidylcholinesMetaboliteCHEBI:49183 (ChEBI)
taurocholateMetaboliteCHEBI:36257 (ChEBI) AKA cholyltaurine

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
(24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy -5beta-cholestan-26-oyl-CoA3α,7α,12α-trihydroxy-24-oxo-5β-cholestan-26-oyl-CoAmim-conversionR-HSA-193455 (Reactome)
(25R)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestan-26-oyl-CoA(25S)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoAmim-conversionR-HSA-192056 (Reactome)
(25R)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoA(25S)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoAmim-conversion40456 (Rhea)
(25S)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA3alpha,7alpha,12alpha-Trihydroxy-5beta-cholest-24-enoyl-CoAmim-conversionR-HSA-192335 (Reactome)
(25S)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoA3alpha,7alpha-Dihydroxy-5beta-cholest-24-enoyl-CoAmim-conversionR-HSA-193369 (Reactome)
27-Hydroxycholesterol3beta-Hydroxy-5-cholestenoic acidmim-conversion46093 (Rhea)
3alpha,7alpha,12alpha-Trihydroxy-5beta-cholest-24-enoyl-CoA(24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy -5beta-cholestan-26-oyl-CoAmim-conversionR-HSA-192331 (Reactome)
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oic acidmim-conversionR-HSA-192054 (Reactome)
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oic acid(25R)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestan-26-oyl-CoAmim-conversionR-HSA-193401 (Reactome) Activated to CoA-ester at the endoplasmic reticulum.
3alpha,7alpha,24-trihydroxy -5beta-cholestan-26-oyl-CoA3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl-CoAmim-conversionR-HSA-193508 (Reactome)
3alpha,7alpha-Dihydroxy-5beta-cholest-24-enoyl-CoA3alpha,7alpha,24-trihydroxy -5beta-cholestan-26-oyl-CoAmim-conversionR-HSA-193535 (Reactome)
3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl-CoAChenodeoxycholoyl-CoAmim-conversionR-HSA-193533 (Reactome)
3alpha,7alpha-dihydroxy-5beta-cholestan-26-al3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acidmim-conversionR-HSA-193460 (Reactome)
3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid(25R)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoAmim-conversionR-HSA-193424 (Reactome)
3beta,7alpha-Dihydroxy-5-cholestenoate7alpha,26-dihydroxycholest-4-en-3-onemim-conversionR-HSA-193816 (Reactome)
3beta-Hydroxy-5-cholestenoic acid3beta,7alpha-Dihydroxy-5-cholestenoatemim-conversionR-HSA-191972 (Reactome)
3α,7α,12α-trihydroxy-24-oxo-5β-cholestan-26-oyl-CoAcholyl-CoAmim-conversionR-HSA-192341 (Reactome)
5beta-Cholestane-3alpha,7alpha,27-triol3alpha,7alpha-dihydroxy-5beta-cholestan-26-almim-conversionR-HSA-193497 (Reactome)
5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-almim-conversionR-HSA-192042 (Reactome)
5beta-cholestane-3alpha,7alpha,12alpha-triol5beta-cholestane-3alpha,7alpha,12alpha,26-tetrolmim-conversionR-HSA-191999 (Reactome)
5beta-cholestane-3alpha,7alpha,26-triol3alpha,7alpha-dihydroxy-5beta-cholestan-26-almim-conversionR-HSA-193497 (Reactome)
5beta-cholestane-3alpha,7alpha-diol5beta-Cholestane-3alpha,7alpha,27-triolmim-conversionR-HSA-193393 (Reactome)
7-alpha-Hydroxycholesterol7alpha-Hydroxy-4-cholesten-3-onemim-conversion11897 (Rhea)
7alpha,12alpha-Dihydroxy-4-cholesten-3-one7alpha,12alpha-dihydroxy-5beta-cholestan-3-onemim-conversion46633 (Rhea)
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one5beta-cholestane-3alpha,7alpha,12alpha-triolmim-conversionR-HSA-192036 (Reactome)
7alpha,26-dihydroxy-5beta-cholestan-3-one5beta-cholestane-3alpha,7alpha,26-triolmim-conversionR-HSA-193841 (Reactome)
7alpha,26-dihydroxycholest-4-en-3-one7alpha,26-dihydroxy-5beta-cholestan-3-onemim-conversionR-HSA-193824 (Reactome)
7alpha-Hydroxy-4-cholesten-3-one7alpha,12alpha-Dihydroxy-4-cholesten-3-onemim-conversionR-HSA-192033 (Reactome)
7alpha-Hydroxy-4-cholesten-3-one7alpha-hydroxy-5beta-cholestan-3-onemim-conversion46641 (Rhea)
7alpha-hydroxy-5beta-cholestan-3-one5beta-cholestane-3alpha,7alpha-diolmim-conversionR-HSA-192160 (Reactome)
Bile acidBile acidArrowR-HSA-193362 (Reactome)
Bilirubin glucuronideBilirubin glucuronideArrowR-HSA-5679041 (Reactome)
Chenodeoxycholoyl-CoAGlycochenodeoxycholic acidmim-conversion49789 (Rhea)
Chenodeoxycholoyl-CoATaurochenodeoxycholic acidmim-conversion49785 (Rhea)
Glycochenodeoxycholic acidchenodeoxycholate(1-)mim-conversion47114 (Rhea) Enzymatic step: intraluminal bacterial deconjugation
Glycocholic acidcholatemim-conversion19354 (Rhea) Enzymatic step: intraluminal bacterial deconjugation
PhosphatidylserinePhosphatidylserineArrowR-HSA-939763 (Reactome)
Taurochenodeoxycholic acidchenodeoxycholate(1-)mim-conversion16310 (Rhea) Enzymatic step: intraluminal bacterial deconjugation
Taurocholic acidcholatemim-conversion47110 (Rhea) Enzymatic step: intraluminal bacterial deconjugation. Hydrolysis of taurocholic acid yields taurine.
chenodeoxycholate(1-)Chenodeoxycholoyl-CoAmim-conversion31513 (Rhea)
cholatecholyl-CoAmim-conversion23533 (Rhea)
cholesterol27-Hydroxycholesterolmim-conversion46401 (Rhea)
cholesterol7-alpha-Hydroxycholesterolmim-conversion21813 (Rhea) Hydroxylation
cholyl-CoATaurocholic acidmim-conversion47101 (Rhea)
cholyl-CoAmim-conversion14002 (Rhea)
glycocholateArrowR-HSA-194079 (Reactome)
glycocholateArrowR-HSA-194083 (Reactome)
mim-conversion47110 (Rhea)
phosphatidylcholinesphosphatidylcholinesArrowR-HSA-5678706 (Reactome)
taurocholatetaurocholateArrow71704 (Rhea) Previous annotation Reactome R-HSA-194083
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