Oxysterols derived from cholesterol (Homo sapiens)

From WikiPathways

Revision as of 09:46, 17 April 2023 by Conroy lipids (Talk | contribs)
Jump to: navigation, search
23, 60Peroxisomal side-chain shortening24S- and 25-Hydroxylase pathway7α-Hydroxylase pathway:neutral/classical pathwayof bile acid biosynthesis25-hydroxylase pathway5564825, 26, 58, 5922, 26, 35, 40556020848606060860606086012, 30486024, 60Blood-Brain-Barrier SLOSHSDB15, 28Based on Fig. 1[PMID:31698146]56, 62NPC134CD4+ Th17 cellsReduction and oxidation (presumably by AKR1D1 and AKR1C4)may precede before or after 24-hydroxylation.LabelINSIGCYP3A4IL-17AAKR1C4CYP7B17α,24R-Dihydroxy-3-oxocholest-4-en-(25R)26-oyl-CoABACS (SLC27A5)7α,12α−Dihydroxycholest-4-en-3-one36CYP3A4AKR1D17β,(25R)26-Dihydroxycholesterol7α-Hydroxy-3-oxocholest-4,24(E)-dien-26-oyl-CoACYP27A1histamineDHCR7HSD3B79ACOT1EBI27α-Hydroxy-3-oxochol-4-en-24-oyl-CoAHSD3B7CYP8B17α(25S)26-DihydroxycholesterolHSD3B760DBPLXR-alphaACOX23α,7α,12α−Trihydroxy-5β-cholestan-(25R)26-oic acid7-Oxocholesterol and7β-Hydroxycholesterol pathwaysD8D7I97α-Hydroxy-3-oxochol-4-en-24-oyl-taurineDendrogenin A8CYP27A1BAATEBI2AMACR365β-Cholestane-3α,7α,12α,(25R)26-tetrolCholesterol7α,24S-Dihydroxy-3-oxocholest-4-en-(25R)26-oic acidSCPx (SCP2)7α,25-Dihydroxycholest-4-en-3-oneAKR1C4CYP3A432, 60Estrogen receptor alpha7α-Hydroxy-3-oxocholest-4-en-(25S)26-oyl-CoA24S-hydroxycholesterol 7α-Hydroxy-3-oxocholest-4-en-(25R)26-oyl-CoA7α,24S-Dihydroxy-3-oxocholest-4-en-(25R)26-oyl CoA7α,12α,(25R)26-Trihydroxy-5β-cholestan-3-oneAKR1D1LBPCYP8B13β,7α-Dihydroxycholest-5-en-(25R)26-oic acid60PXR7α,25-Dihydroxycholesterol7α-Hydroxy-3-oxochol-4-en-24-oic acid247α-Hydroxy-3-oxochol-4-en-24-oyl-glycineROR-γt 527α−Hydroxycholest-4-en-3-one607α-Hydroxy-3,24-bisoxocholest-4-en-(25R)26-oyl-CoAACOTVLCS (SLC27A2)5α,6α-Epoxycholesterol36Cholestane-3β,5α,6β-triol7β-Hydroxycholesterol7α-Hydroxycholesterol25-Hydroxycholesterol 7α,25-Dihydroxycholesterol3, 13, 42, 4312, 30(25R)26-Hydroxycholesterol7α,(25R)26-Dihydroxycholesterol44, 60885, 16, 31, 54, 6041, 54, 6039, 46, 50, 54, 60...6014, 17, 21, 60CYP27A1CYP27A137, 60, 6137, 61CYP7A1CYP27A160CYP7B137, 60, 6160CH25HCYP46A160ChEH36836IL-17BIL-17CIL-17DIL-17EIL-17F48Estrogen receptor beta48LXR-betaCTX7, 28, 47SPG515, 28NP Type B57NP type A577α−Hydroxycholest-4-en-3-one60607α-Hydroxycholesterol607α(25S)26-Dihydroxycholest-4-en-3-one24, 60607α,12α−Dihydroxy-5β-cholestan-3-one5β-Cholestane-3α,7α,12α−triolCYP27A13β-Hydroxycholest-5-en-(25R)-26-oicacid37, 60, 6154, 60CYP27A16037, 60, 61607α,(25R)26−Dihydroxycholest-4-en-3-one607α-Hydroxy-3-oxocholest-4-en-(25R)26-oic acid606060CYP27A1CYP27A160607α, 12α,(25R)26−Trihydroxycholest-4-en-3-one606060607α,12α-Dihydroxy-3-oxocholest-4-en-(25R)26-oic acid6060CYP8B160607α,12α-Dihydroxy-3-oxo-5β-cholestan-(25R)26-oic acid606060AKR1D1CYP27A160Based on Fig. 1[PMID:31698146]CYP8B17α,12α,25-Trihydroxycholest-4-en-3-one7α,25-Dihydroxycholest-4-en-3-one7α,25-Dihydroxy-3-oxocholest-4-en-26-oic acid7α,12α-Dihydroxy-3-oxochol-4-en-24-oic107α,12α,25-Trihydroxycholest-4-en-3,24-dioneCholic acid7α,12α,24,25-Tetrahydroxycholest-4-en-3-one367α,24S-Dihydroxycholest-4-en-3-oneHSD3B7CYP39A17α,24S-Dihydroxy-3-oxocholest-4-en-(25R)26-oic acid3610, 18CYP27A17α,24S-Dihydroxycholesterol,5346, 60606032, 6060601, 60601, 6018, 6018, 60AKR1C418Based on Fig. 2[PMID:31698146]LXR-alphaLXR-beta24S-Hydroxycholesterol22, 35, 4022, 35, 40EBI2207α-Hydroxy-3-oxocholest-4-en-(25R)26-oic acid6060606060606045, 49, 606060606060Based on Fig. 3[PMID:31698146]AMACRD4, 38CBAS633ACOT245, 49, 602, 51ACOT4ACOT651ACOT7ACOT8ACOT9ACOT11ACOT12ACOT13ACOT7LACOT15DBPD19LKDMN29FHCA11BACS (SLC27A5)36VLCS (SLC27A2)36Wolman DiseaseCholic acid53Chenodeoxycholic acidAKR1D1AKR1C4BACS (SLC27A5)36AMACR36ACOX2DBPSCPx (SCP2)ACOT3β,7β-Dihydroxycholest-5-en(25R)26-oic acidCYP27A137, 613β,7β-Dihydroxychol-5-en-24-oic acid7-DehydrocholesterolDHCR77-OxocholesterolHSD11B126-Hydroxy-7-oxocholesterol3β-Hydroxy-7-oxocholest-5-en-(25R)26-oic acid3β-Hydroxy-7-oxochol-5-en-24-oic acidCYP27A137, 613β,5α-Dihydroxycholestan-6-oneHSD11B2812, 3018


Description

The Oxysterol group of compounds are oxygenated derivatives of cholesterol or its sterol precursors, e.g. 7-dehydrocholesterol (7-DHC) or desmosterol. There are three mechanisms leading to the formation of oxysterols: 1) Enzymatically (first steps of sterol metabolism, being intermediates for the formation of steroid hormones, bile acids and 1,25-dihydroxyvitamin D3), 2) Non-enzymatically by encountering reactive oxygen species (ROS), providing a second pool of metabolites (this pool also includes oxidized cholesterol molecules taken in from diet), see https://www.wikipathways.org/instance/WP5064, and 3) Generation by the gut microflora and uptake through the enterohepatic circulation.

Previously oxysterols where though to be inactive metabolic intermediates, however recent findings have established that these metabolites are involved in cholesterol homoeostasis, can be ligands to nuclear and G protein-coupled receptors and biomarkers of diseases (for example Niemann-Pick disease).

This pathway drawing was inspired by Figure 3 of the review article by Griffiths et al. 2016, and has been extended with immune system, receptor agonists, steroidal alkaloid and biomarker information from the same paper. This pathway has been updated with Figure 1 from Griffiths et al. 2020 (green areas), Figure 2 (yellow area) and Figure 3 (blue area).

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Honda A, Miyazaki T, Ikegami T, Iwamoto J, Maeda T, Hirayama T, Saito Y, Teramoto T, Matsuzaki Y; ''Cholesterol 25-hydroxylation activity of CYP3A.''; J Lipid Res, 2011 PubMed Europe PMC Scholia
  2. Griffiths WJ, Wang Y; ''Oxysterols as lipid mediators: Their biosynthetic genes, enzymes and metabolites.''; Prostaglandins Other Lipid Mediat, 2020 PubMed Europe PMC Scholia
  3. Björkhem I; ''Cerebrotendinous xanthomatosis.''; Curr Opin Lipidol, 2013 PubMed Europe PMC Scholia
  4. Setchell KD, Heubi JE, Shah S, Lavine JE, Suskind D, Al-Edreesi M, Potter C, Russell DW, O'Connell NC, Wolfe B, Jha P, Zhang W, Bove KE, Knisely AS, Hofmann AF, Rosenthal P, Bull LN; ''Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency.''; Gastroenterology, 2013 PubMed Europe PMC Scholia
  5. Song C, Liao S; ''Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha.''; Endocrinology, 2000 PubMed Europe PMC Scholia
  6. Cheng JB, Jacquemin E, Gerhardt M, Nazer H, Cresteil D, Heubi JE, Setchell KD, Russell DW; ''Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease.''; J Clin Endocrinol Metab, 2003 PubMed Europe PMC Scholia
  7. Hunt MC, Rautanen A, Westin MA, Svensson LT, Alexson SE; ''Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs.''; FASEB J, 2006 PubMed Europe PMC Scholia
  8. 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
  9. Ferdinandusse S, Ylianttila MS, Gloerich J, Koski MK, Oostheim W, Waterham HR, Hiltunen JK, Wanders RJ, Glumoff T; ''Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis.''; Am J Hum Genet, 2006 PubMed Europe PMC Scholia
  10. Rosen H, Reshef A, Maeda N, Lippoldt A, Shpizen S, Triger L, Eggertsen G, Björkhem I, Leitersdorf E; ''Markedly reduced bile acid synthesis but maintained levels of cholesterol and vitamin D metabolites in mice with disrupted sterol 27-hydroxylase gene.''; J Biol Chem, 1998 PubMed Europe PMC Scholia
  11. de Medina P, Paillasse MR, Segala G, Poirot M, Silvente-Poirot S; ''Identification and pharmacological characterization of cholesterol-5,6-epoxide hydrolase as a target for tamoxifen and AEBS ligands.''; Proc Natl Acad Sci U S A, 2010 PubMed Europe PMC Scholia
  12. Lund EG, Guileyardo JM, Russell DW; ''cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain.''; Proc Natl Acad Sci U S A, 1999 PubMed Europe PMC Scholia
  13. Radhakrishnan A, Ikeda Y, Kwon HJ, Brown MS, Goldstein JL; ''Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig.''; Proc Natl Acad Sci U S A, 2007 PubMed Europe PMC Scholia
  14. Porter FD, Scherrer DE, Lanier MH, Langmade SJ, Molugu V, Gale SE, Olzeski D, Sidhu R, Dietzen DJ, Fu R, Wassif CA, Yanjanin NM, Marso SP, House J, Vite C, Schaffer JE, Ory DS; ''Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease.''; Sci Transl Med, 2010 PubMed Europe PMC Scholia
  15. Russell DW; ''The enzymes, regulation, and genetics of bile acid synthesis.''; Annu Rev Biochem, 2003 PubMed Europe PMC Scholia
  16. Griffiths WJ, Abdel-Khalik J, Yutuc E, Roman G, Warner M, Gustafsson JÅ, Wang Y; ''Concentrations of bile acid precursors in cerebrospinal fluid of Alzheimer's disease patients.''; Free Radic Biol Med, 2019 PubMed Europe PMC Scholia
  17. Shackleton CH; ''Role of a disordered steroid metabolome in the elucidation of sterol and steroid biosynthesis.''; Lipids, 2012 PubMed Europe PMC Scholia
  18. Klinke G, Rohrbach M, Giugliani R, Burda P, Baumgartner MR, Tran C, Gautschi M, Mathis D, Hersberger M; ''LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases.''; Clin Biochem, 2015 PubMed Europe PMC Scholia
  19. Soroosh P, Wu J, Xue X, Song J, Sutton SW, Sablad M, Yu J, Nelen MI, Liu X, Castro G, Luna R, Crawford S, Banie H, Dandridge RA, Deng X, Bittner A, Kuei C, Tootoonchi M, Rozenkrants N, Herman K, Gao J, Yang XV, Sachen K, Ngo K, Fung-Leung WP, Nguyen S, de Leon-Tabaldo A, Blevitt J, Zhang Y, Cummings MD, Rao T, Mani NS, Liu C, McKinnon M, Milla ME, Fourie AM, Sun S; ''Oxysterols are agonist ligands of RORγt and drive Th17 cell differentiation.''; Proc Natl Acad Sci U S A, 2014 PubMed Europe PMC Scholia
  20. Bodin K, Andersson U, Rystedt E, Ellis E, Norlin M, Pikuleva I, Eggertsen G, Björkhem I, Diczfalusy U; ''Metabolism of 4 beta -hydroxycholesterol in humans.''; J Biol Chem, 2002 PubMed Europe PMC Scholia
  21. Norlin M, Toll A, Björkhem I, Wikvall K; ''24-hydroxycholesterol is a substrate for hepatic cholesterol 7alpha-hydroxylase (CYP7A).''; J Lipid Res, 2000 PubMed Europe PMC Scholia
  22. Pikuleva IA, Babiker A, Waterman MR, Björkhem I; ''Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative bile acid biosynthetic pathways.''; J Biol Chem, 1998 PubMed Europe PMC Scholia
  23. de Medina P, Diallo K, Huc-Claustre E, Attia M, Soulès R, Silvente-Poirot S, Poirot M; ''The 5,6-epoxycholesterol metabolic pathway in breast cancer: Emergence of new pharmacological targets.''; Br J Pharmacol, 2021 PubMed Europe PMC Scholia
  24. Nelson ER, Wardell SE, Jasper JS, Park S, Suchindran S, Howe MK, Carver NJ, Pillai RV, Sullivan PM, Sondhi V, Umetani M, Geradts J, McDonnell DP; ''27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology.''; Science, 2013 PubMed Europe PMC Scholia
  25. Lund EG, Kerr TA, Sakai J, Li WP, Russell DW; ''cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism.''; J Biol Chem, 1998 PubMed Europe PMC Scholia
  26. Jones JM, Gould SJ; ''Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase.''; Biochem Biophys Res Commun, 2000 PubMed Europe PMC Scholia
  27. Hunt MC, Siponen MI, Alexson SE; ''The emerging role of acyl-CoA thioesterases and acyltransferases in regulating peroxisomal lipid metabolism.''; Biochim Biophys Acta, 2012 PubMed Europe PMC Scholia
  28. Fakheri RJ, Javitt NB; ''27-Hydroxycholesterol, does it exist? On the nomenclature and stereochemistry of 26-hydroxylated sterols.''; Steroids, 2012 PubMed Europe PMC Scholia
  29. Jelinek DF, Andersson S, Slaughter CA, Russell DW; ''Cloning and regulation of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis.''; J Biol Chem, 1990 PubMed Europe PMC Scholia
  30. Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, Asplund A, Sjöstedt E, Lundberg E, Szigyarto CA, Skogs M, Takanen JO, Berling H, Tegel H, Mulder J, Nilsson P, Schwenk JM, Lindskog C, Danielsson F, Mardinoglu A, Sivertsson A, von Feilitzen K, Forsberg M, Zwahlen M, Olsson I, Navani S, Huss M, Nielsen J, Ponten F, Uhlén M; ''Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics.''; Mol Cell Proteomics, 2014 PubMed Europe PMC Scholia
  31. Li-Hawkins J, Lund EG, Bronson AD, Russell DW; ''Expression cloning of an oxysterol 7alpha-hydroxylase selective for 24-hydroxycholesterol.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
  32. Blanc M, Hsieh WY, Robertson KA, Kropp KA, Forster T, Shui G, Lacaze P, Watterson S, Griffiths SJ, Spann NJ, Meljon A, Talbot S, Krishnan K, Covey DF, Wenk MR, Craigon M, Ruzsics Z, Haas J, Angulo A, Griffiths WJ, Glass CK, Wang Y, Ghazal P; ''The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response.''; Immunity, 2013 PubMed Europe PMC Scholia
  33. Bauman DR, Bitmansour AD, McDonald JG, Thompson BM, Liang G, Russell DW; ''25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production.''; Proc Natl Acad Sci U S A, 2009 PubMed Europe PMC Scholia
  34. DuSell CD, Umetani M, Shaul PW, Mangelsdorf DJ, McDonnell DP; ''27-hydroxycholesterol is an endogenous selective estrogen receptor modulator.''; Mol Endocrinol, 2008 PubMed Europe PMC Scholia
  35. de Medina P, Paillasse MR, Segala G, Voisin M, Mhamdi L, Dalenc F, Lacroix-Triki M, Filleron T, Pont F, Saati TA, Morisseau C, Hammock BD, Silvente-Poirot S, Poirot M; ''Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties.''; Nat Commun, 2013 PubMed Europe PMC Scholia
  36. Hannedouche S, Zhang J, Yi T, Shen W, Nguyen D, Pereira JP, Guerini D, Baumgarten BU, Roggo S, Wen B, Knochenmuss R, Noël S, Gessier F, Kelly LM, Vanek M, Laurent S, Preuss I, Miault C, Christen I, Karuna R, Li W, Koo DI, Suply T, Schmedt C, Peters EC, Falchetto R, Katopodis A, Spanka C, Roy MO, Detheux M, Chen YA, Schultz PG, Cho CY, Seuwen K, Cyster JG, Sailer AW; ''Oxysterols direct immune cell migration via EBI2.''; Nature, 2011 PubMed Europe PMC Scholia
  37. Lütjohann D, Breuer O, Ahlborg G, Nennesmo I, Sidén A, Diczfalusy U, Björkhem I; ''Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain intothe circulation.''; Proc Natl Acad Sci U S A, 1996 PubMed Europe PMC Scholia
  38. Wu Z, Martin KO, Javitt NB, Chiang JY; ''Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1.''; J Lipid Res, 1999 PubMed Europe PMC Scholia
  39. Noshiro M, Okuda K; ''Molecular cloning and sequence analysis of cDNA encoding human cholesterol 7 alpha-hydroxylase.''; FEBS Lett, 1990 PubMed Europe PMC Scholia
  40. Clayton PT; ''Disorders of bile acid synthesis.''; J Inherit Metab Dis, 2011 PubMed Europe PMC Scholia
  41. Reboldi A, Dang EV, McDonald JG, Liang G, Russell DW, Cyster JG; ''''; , PubMed Europe PMC Scholia
  42. Umetani M, Domoto H, Gormley AK, Yuhanna IS, Cummins CL, Javitt NB, Korach KS, Shaul PW, Mangelsdorf DJ; ''27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen.''; Nat Med, 2007 PubMed Europe PMC Scholia
  43. Griffiths WJ, Crick PJ, Meljon A, Theofilopoulos S, Abdel-Khalik J, Yutuc E, Parker JE, Kelly DE, Kelly SL, Arenas E, Wang Y; ''Additional pathways of sterol metabolism: Evidence from analysis of Cyp27a1-/- mouse brain and plasma.''; Biochim Biophys Acta Mol Cell Biol Lipids, 2019 PubMed Europe PMC Scholia
  44. Autio KJ, Schmitz W, Nair RR, Selkälä EM, Sormunen RT, Miinalainen IJ, Crick PJ, Wang Y, Griffiths WJ, Reddy JK, Baes M, Hiltunen JK; ''Role of AMACR (α-methylacyl-CoA racemase) and MFE-1 (peroxisomal multifunctional enzyme-1) in bile acid synthesis in mice.''; Biochem J, 2014 PubMed Europe PMC Scholia
  45. Theofilopoulos S, Griffiths WJ, Crick PJ, Yang S, Meljon A, Ogundare M, Kitambi SS, Lockhart A, Tuschl K, Clayton PT, Morris AA, Martinez A, Reddy MA, Martinuzzi A, Bassi MT, Honda A, Mizuochi T, Kimura A, Nittono H, De Michele G, Carbone R, Criscuolo C, Yau JL, Seckl JR, Schüle R, Schöls L, Sailer AW, Kuhle J, Fraidakis MJ, Gustafsson JÅ, Steffensen KR, Björkhem I, Ernfors P, Sjövall J, Arenas E, Wang Y; ''Cholestenoic acids regulate motor neuron survival via liver X receptors.''; J Clin Invest, 2014 PubMed Europe PMC Scholia
  46. Yantsevich AV, Dichenko YV, Mackenzie F, Mukha DV, Baranovsky AV, Gilep AA, Usanov SA, Strushkevich NV; ''Human steroid and oxysterol 7α-hydroxylase CYP7B1: substrate specificity, azole binding and misfolding of clinically relevant mutants.''; FEBS J, 2014 PubMed Europe PMC Scholia
  47. Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, Sundseth SS, Winegar DA, Blanchard DE, Spencer TA, Willson TM; ''Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway.''; J Biol Chem, 1997 PubMed Europe PMC Scholia
  48. Griffiths WJ, Yutuc E, Abdel-Khalik J, Crick PJ, Hearn T, Dickson A, Bigger BW, Hoi-Yee Wu T, Goenka A, Ghosh A, Jones SA, Covey DF, Ory DS, Wang Y; ''Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders.''; Free Radic Biol Med, 2019 PubMed Europe PMC Scholia
  49. Dussault I, Yoo HD, Lin M, Wang E, Fan M, Batta AK, Salen G, Erickson SK, Forman BM; ''Identification of an endogenous ligand that activates pregnane X receptor-mediated sterol clearance.''; Proc Natl Acad Sci U S A, 2003 PubMed Europe PMC Scholia
  50. 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
  51. Abdel-Khalik J, Hearn T, Dickson AL, Crick PJ, Yutuc E, Austin-Muttitt K, Bigger BW, Morris AA, Shackleton CH, Clayton PT, Iida T, Sircar R, Rohatgi R, Marschall HU, Sjövall J, Björkhem I, Mullins JGL, Griffiths WJ, Wang Y; ''Bile acid biosynthesis in Smith-Lemli-Opitz syndrome bypassing cholesterol: Potential importance of pathway intermediates.''; J Steroid Biochem Mol Biol, 2021 PubMed Europe PMC Scholia
  52. Ogundare M, Theofilopoulos S, Lockhart A, Hall LJ, Arenas E, Sjövall J, Brenton AG, Wang Y, Griffiths WJ; ''Cerebrospinal fluid steroidomics: are bioactive bile acids present in brain?''; J Biol Chem, 2010 PubMed Europe PMC Scholia
  53. He S, Nelson ER; ''27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator.''; Maturitas, 2017 PubMed Europe PMC Scholia
  54. Mast N, Norcross R, Andersson U, Shou M, Nakayama K, Bjorkhem I, Pikuleva IA; ''Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain.''; Biochemistry, 2003 PubMed Europe PMC Scholia
  55. Toll A, Wikvall K, Sudjana-Sugiaman E, Kondo KH, Björkhem I; ''7 alpha hydroxylation of 25-hydroxycholesterol in liver microsomes. Evidence that the enzyme involved is different from cholesterol 7 alpha-hydroxylase.''; Eur J Biochem, 1994 PubMed Europe PMC Scholia
  56. Mast N, White MA, Bjorkhem I, Johnson EF, Stout CD, Pikuleva IA; ''Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain.''; Proc Natl Acad Sci U S A, 2008 PubMed Europe PMC Scholia
  57. Villey I, de Chasseval R, de Villartay JP; ''RORgammaT, a thymus-specific isoform of the orphan nuclear receptor RORgamma / TOR, is up-regulated by signaling through the pre-T cell receptor and binds to the TEA promoter.''; Eur J Immunol, 1999 PubMed Europe PMC Scholia
  58. Diczfalusy U, Olofsson KE, Carlsson AM, Gong M, Golenbock DT, Rooyackers O, Fläring U, Björkbacka H; ''Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide.''; J Lipid Res, 2009 PubMed Europe PMC Scholia
  59. Hunt MC, Solaas K, Kase BF, Alexson SE; ''''; , PubMed Europe PMC Scholia
  60. Vaz FM, Ferdinandusse S; ''Bile acid analysis in human disorders of bile acid biosynthesis.''; Mol Aspects Med, 2017 PubMed Europe PMC Scholia
  61. Griffiths WJ, Abdel-Khalik J, Hearn T, Yutuc E, Morgan AH, Wang Y; ''Current trends in oxysterol research.''; Biochem Soc Trans, 2016 PubMed Europe PMC Scholia
  62. Abdel-Khalik J, Crick PJ, Yutuc E, DeBarber AE, Duell PB, Steiner RD, Laina I, Wang Y, Griffiths WJ; ''Identification of 7α,24-dihydroxy-3-oxocholest-4-en-26-oic and 7α,25-dihydroxy-3-oxocholest-4-en-26-oic acids in human cerebrospinal fluid and plasma.''; Biochimie, 2018 PubMed Europe PMC Scholia
  63. Björkhem I, Lütjohann D, Diczfalusy U, Ståhle L, Ahlborg G, Wahren J; ''Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation.''; J Lipid Res, 1998 PubMed Europe PMC Scholia
  64. Liu C, Yang XV, Wu J, Kuei C, Mani NS, Zhang L, Yu J, Sutton SW, Qin N, Banie H, Karlsson L, Sun S, Lovenberg TW; ''Oxysterols direct B-cell migration through EBI2.''; Nature, 2011 PubMed Europe PMC Scholia
  65. 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

History

View all...
CompareRevisionActionTimeUserComment
128535view18:11, 11 February 2024EweitzOntology Term : 'CD4-positive helper T cell' added !
128534view18:11, 11 February 2024EweitzFix typos, soften disease color, standardize case
127388view19:59, 27 September 2023Conroy lipidsfix type of missing attribute
126793view14:16, 22 June 2023DeSlConnected unconnected lines
126778view09:31, 22 June 2023Conroy lipidsadd 5,6-ECS, more GlcNag BAs
126777view07:56, 22 June 2023Conroy lipidscorrected lipid ID, added enzymes and further reaction from 33246156
126485view21:02, 8 May 2023AlexanderPicofixed links in description
126234view09:46, 17 April 2023Conroy lipidsconvert lipid metabolites to LIPID MAPS IDs
126202view14:20, 14 April 2023Conroy lipidscorrected 7α,25-Dihydroxy-3-oxocholest -5-en-26-oic acid to -4-en-. updated ID to lipidmaps
125491view10:10, 20 February 2023EgonwModified description
125487view09:27, 20 February 2023WilliamJGriffithsModified description
125481view06:29, 20 February 2023RobertAndrewsModified description
123863view20:16, 20 August 2022EgonwLipidMaps ID seems to have been replaced.
123769view13:47, 12 August 2022EgonwModern Uniprot data source
123764view13:10, 12 August 2022EgonwMade a pathway clickable
123711view12:48, 11 August 2022Conroy lipidsupdated with modifications made by Bill Griffiths offline
121824view07:02, 7 March 2022EgonwLipidMaps ID seems to have been replaced.
120921view12:13, 31 January 2022Conroy lipidscorrected ID for 7a,12a-diHCO. Previous ID was for 7a-HCO
120411view09:29, 30 November 2021Fehrhartboxed pathway node
116235view14:54, 21 April 2021DeSlLast updates to LIPIDMAPS IDs
116234view14:49, 21 April 2021DeSlAdded more LIPIDMAPS IDs
116233view14:40, 21 April 2021DeSlStarted adding LIPIDMAPS IDs again, without UTF-8 encoding issues
116228view14:32, 21 April 2021DeSlReverted to version '10:06, 31 March 2021' by DeSl
116222view09:15, 21 April 2021Conroy lipidsupdated IDs to lipidmaps identifiers from inchikey- inchikey was not giving any cross refs to other DBs
116029view10:06, 31 March 2021DeSlSmall layout change
115605view12:23, 1 March 2021DeSlConnected unconnected line to INSIG
115603view12:20, 1 March 2021DeSl
115586view10:34, 1 March 2021DeSlAdded WP5064 linkout for more details on Fig.4
115571view05:58, 27 February 2021EgonwRemoved a few more InChIKeys with their respective PubChem CIDs
115570view05:52, 27 February 2021EgonwRemoved a number of InChIKeys with their respective PubChem CIDs
115566view18:33, 26 February 2021DeSlOntology Term : 'alpha-methylacyl-CoA racemase deficiency' added !
115565view18:32, 26 February 2021DeSlOntology Term : 'congenital bile acid synthesis defect 6' added !
115564view18:32, 26 February 2021DeSlOntology Term : 'congenital bile acid synthesis defect' added !
115563view18:31, 26 February 2021DeSlOntology Term : 'D-bifunctional protein deficiency' added !
115562view18:29, 26 February 2021DeSlOntology Term : 'familial hypercholanemia pathway' added !
115561view18:28, 26 February 2021DeSl
115560view18:26, 26 February 2021DeSlAdded other missing proteins from Fig.3
115559view18:16, 26 February 2021DeSlAdded diseases for DBP, ACPx and BAAT
115558view18:07, 26 February 2021DeSlAdded BAAT + refs
115557view17:47, 26 February 2021DeSlAdded ACOT
115556view16:41, 26 February 2021DeSlAdded DBP
115555view16:33, 26 February 2021DeSlAdded ACOX2 and accompanying IEM
115552view16:23, 26 February 2021DeSlAdded AMACR protein + disease
115548view15:49, 26 February 2021DeSlAdded first proteins including refs.
115547view15:35, 26 February 2021DeSlConnected last metabolites from Fig.3
115546view15:31, 26 February 2021DeSlAdded metabolites from Fig.3
115536view11:09, 26 February 2021DeSlAdded more refs for bidning to LXR, INSIGa nd estrogen receptors.
115535view10:44, 26 February 2021DeSlAdded last lit. refs for Fig.2
115532view10:28, 26 February 2021DeSlAdded BBB-crossover for 24S-HC
115531view10:22, 26 February 2021DeSlAdded binding of 24S-HC as ligand

External references

DataNodes

View all...
NameTypeDatabase referenceComment
7α,25-DihydroxycholesterolMetaboliteLMST04030166 (LIPID MAPS)
  • AKA 7α,25-Dihydroxycholesterol
  • Involved in immune response (agonist of G-protein-coupled receptor EBI2 (AKA GPR183)) [PMID: 21796212, 21796211].
7α-Hydroxy-3-oxocholest-4-en -(25R)26-oyl-CoAMetaboliteLMST04030252 (LIPID MAPS) aka 7α-Hydroxy-3-oxocholest-4-en-(25R)26-oyl-CoA
(25R)26-Hydroxycholesterol MetaboliteLMST01010088 (LIPID MAPS)
  • "AKA (25R)26-hydroxycholesterol; Named with systematic nomenclature, where hydroxylation at the terminal side chain of cholesterol is on C-26 leading to 26-hydroxycholesterol (26-HC) which may have 25R or 25S stereochemistry [26]. Unless stated otherwise 25R stereochemistry is assumed. In much of the literature (25R)26-HC is referred to 27-hydroxycholesterol (27-HC), presumably the 25R isomer." [PMID:22366074]
  • "26-HC, 25R-stereochemistry is assumed unless indicated otherwise, also called 27-hydroxycholesterol" [PMID:31698146]
24S-HydroxycholesterolMetaboliteLMST01010019 (LIPID MAPS)
  • AKA (24S)-hydroxycholesterol
  • Can corss the Blood-Brain-Barrier (to remove cholesterol from brain tissue) [PMID:8790411; 9717719]
24S-hydroxycholesterolMetaboliteLMST01010019 (LIPID MAPS)
  • AKA 24S-hydroxycholesterol
  • Can corss the Blood-Brain-Barrier (to remove cholesterol from brain tissue) [PMID:8790411; 9717719]
25-HydroxycholesterolMetaboliteLMST01010018 (LIPID MAPS)
  • AKA 25-Hydroxycholesterol
  • Produced by macrophages [PMID: 19805370, 19502589, 23273843], in vivo [PMID: 25104388].
26-Hydroxy-7-oxocholesterolMetaboliteLMST04030180 (LIPID MAPS)
3α,7α,12α−Trihydroxy-5β-cholestan -(25R)26-oic acidMetaboliteLMST04030151 (LIPID MAPS) AKA (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oic acid
3β,5α-Dihydroxycholestan-6-oneMetaboliteLMST01010126 (LIPID MAPS)
3β,7α-Dihydroxycholest

-5-en-(25R)26-oic

acid		MetaboliteLMST04030241 (LIPID MAPS) Aka 3β,7α-dihydroxycholest-5-en-(25R)26-oic acid
3β,7β-Dihydroxychol-5-en-24-oic acidMetaboliteLMST04010280 (LIPID MAPS)
3β,7β-Dihydroxycholest-5-en(25R)26-oic acidMetaboliteLMST04030235 (LIPID MAPS)
3β-Hydroxy-7-oxochol-5-en- 24-oic acidMetaboliteLMST04010394 (LIPID MAPS)
3β-Hydroxy-7-oxocholest-5-en- (25R)26-oic acidMetaboliteLMST04030239 (LIPID MAPS)
3β-Hydroxycholest

-5-en-(25R)-26-oic

acid		MetaboliteLMST04030072 (LIPID MAPS)
  • "AKA (25R)-3beta-hydroxycholest-5-en-26-oic acid; 3β-HC-5-en-(25R)26-oic acid
  • "Pathway starting from this metabolite to 3β,7alpha-HCA is considered the acidic or alternative PW of bile acid biosynthesis" [PMID:31698146,12543708]
5α,6α-EpoxycholesterolMetaboliteLMST01010011 (LIPID MAPS) AKA 5,6α-epoxycholesterol
5β-Cholestane-

3α,7α,12α,(25R)26-

tetrol		MetaboliteLMST04030160 (LIPID MAPS) aka (25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol
5β-Cholestane-3α,7α,12α−triolMetaboliteLMST04030035 (LIPID MAPS) aka 5beta-cholestane-3alpha,7alpha,12alpha-triol ; trihydroxycoprostane
7-DehydrocholesterolMetaboliteLMST01010069 (LIPID MAPS)
7-Oxocholesterol and 7β-Hydroxycholesterol pathwaysPathwayWP5064 (WikiPathways)
7-OxocholesterolMetaboliteLMST01010049 (LIPID MAPS)
7α(25S)26- DihydroxycholesterolMetaboliteLMST01010466 (LIPID MAPS) aka 7α,(25S)26-dihydroxycholesterol
7α(25S)26-Dihydroxycholest -4-en-3-oneMetaboliteLMST01010465 (LIPID MAPS) aka 7α,(25S)26-dihydroxycholest-4-en-3-one
7α, 12α,(25R)26−

Trihydroxycholest

-4-en-3-one		MetaboliteLMST01010464 (LIPID MAPS) aka 7alpha,12alpha,(25R)26-trihydroxycholest-4-en-3-one
7α,(25R)26-DihydroxycholesterolMetaboliteLMST01010462 (LIPID MAPS) AKA 7α,26-dihydroxycholesterol; 7-alpha, (25R)26-diHC
7α,(25R)26−Dihydroxycholest -4-en-3-oneMetaboliteLMST01010463 (LIPID MAPS) aka (25R)-7alpha,26-dihydroxycholest-4-en-3-one
7α,12α,(25R)26-

Trihydroxy-5β-

cholestan-3-one		MetaboliteLMST04030246 (LIPID MAPS) aka 7α,12α,(25R)26-TriHydroxy-5β-cholestan-3-one
7α,12α,24,25-Tetrahydroxycholest -4-en-3-oneMetaboliteLMST04030248 (LIPID MAPS) aka 7α,12α,24,25-Tetrahydroxycholest-4-en-3-one
7α,12α,25-Trihydroxycholest -4-en-3,24-dioneMetaboliteLMST04030249 (LIPID MAPS) aka 7α,12α,25-Trihydroxycholest-4-en-3,24-dione
7α,12α,25-Trihydroxycholest -4-en-3-oneMetaboliteLMST04030105 (LIPID MAPS) aka 7α,12α,25-Trihydroxycholest-4-en-3-one
7α,12α-Dihydroxy

-3-oxocholest-4-en-

(25R)26-oic acid		MetaboliteLMST04030243 (LIPID MAPS) aka 7-alpha,12-alpha-diHydroxy-3-oxocholest-4-en-(25R)26-oic acid (not available in Wikidata)
7α,12α-Dihydroxy-3-oxo-5β- cholestan-(25R)26-oic acidMetaboliteLMST04030245 (LIPID MAPS) aka 7α,12α-diHydroxy-3-oxo-5β-cholestan-(25R)26-oic acid
7α,12α-Dihydroxy-3-oxochol-4-en-24-oicMetaboliteLMST04010241 (LIPID MAPS) aka 7a,12a-Dihydroxy-3-oxochol-4-en-24-oic acid
7α,12α−Dihydroxy-5β-cholestan -3-oneMetaboliteLMST04030113 (LIPID MAPS) aka 7alpha,12alpha-dihydroxy-5beta-cholestan-3-one
7α,12α−Dihydroxycholest -4-en-3-oneMetaboliteLMST04030114 (LIPID MAPS) aka 7alpha-hydroxycholest-4-en-3-one
7α,24R-Dihydroxy-3-oxocholest- 4-en-(25R)26-oyl-CoAMetaboliteLMST04030256 (LIPID MAPS)
7α,24S-Dihydroxy-3-oxocholest -4-en-(25R)26-oic acidMetaboliteLMST04030247 (LIPID MAPS)
  • aka 7α,24S-Dihydroxy-3-oxocholest-4-en-26-oic acid
  • Identified in human plasma [PMID:29960034] and CSF [PMID:30578919,29960034]
7α,24S-Dihydroxy-3-oxocholest- 4-en-(25R)26-oic acidMetaboliteLMST04030247 (LIPID MAPS)
7α,24S-Dihydroxy-3-oxocholest- 4-en-(25R)26-oyl CoAMetaboliteLMST04030251 (LIPID MAPS)
7α,24S-Dihydroxycholest -4-en-3-oneMetaboliteLMST04030216 (LIPID MAPS) aka 7α,24S-Dihydroxycholest-4-en-3-one
7α,24S-Dihydroxycholesterol,MetaboliteLMST04030168 (LIPID MAPS)
  • aka 7α,24S-Dihydroxycholesterol,
  • Found in human plasma [PMID:31009661]
7α,25-Dihydroxy-3-oxocholest -4-en-26-oic acidMetaboliteLMST04030263 (LIPID MAPS)
  • aka 7a,25-Dihydroxy-3-oxocholest-4-en-26-oic acid; 7alpha,25-diH,3O-CA
  • Found in human plasma and cerebrospinal fluid (CSF) [PMID:29960034]; reduced levels found in Alzheimers disease.
7α,25-Dihydroxycholest -4-en-3-oneMetaboliteLMST04030107 (LIPID MAPS) aka 7α,25-Dihydroxycholest-4-en-3-one, 7a,25-diHCO.
7α,25-DihydroxycholesterolMetaboliteLMST04030166 (LIPID MAPS)
  • aka 7α,25-dihydroxycholesterol
  • "the most potent EBI2 agonist 7α,25-dihydroxycholesterol (7α,25-diHC))" [PMID:31698146]
7α-Hydroxy-3,24-bisoxocholest-4- en-(25R)26-oyl-CoAMetaboliteLMST04030254 (LIPID MAPS)
7α-Hydroxy-3-

oxocholest-4-en-

(25R)26-oic acid		MetaboliteLMST04030242 (LIPID MAPS) aka 7-Hydroxy-3-oxocholest-4-en-(25R)26-oic acid
7α-Hydroxy-3-oxochol- 4-en-24-oic acidMetaboliteLMST04010239 (LIPID MAPS)
7α-Hydroxy-3-oxochol- 4-en-24-oyl-CoAMetaboliteLMST04010462 (LIPID MAPS)
7α-Hydroxy-3-oxochol- 4-en-24-oyl-glycineMetaboliteLMST05030020 (LIPID MAPS)
7α-Hydroxy-3-oxochol- 4-en-24-oyl-taurineMetaboliteLMST05040022 (LIPID MAPS)
7α-Hydroxy-3-oxocholest -4-en-(25R)26-oic acidMetaboliteLMST04030242 (LIPID MAPS) aka 7-Hydroxy-3-oxocholest-4-en-(25R)26-oic acid
7α-Hydroxy-3-oxocholest -4-en-(25S)26-oyl-CoAMetaboliteLMST04030253 (LIPID MAPS) aka 7α-Hydroxy-3-oxocholest-4-en-(25S)26-oyl-CoA
7α-Hydroxy-3-oxocholest- 4,24(E)-dien-26-oyl-CoAMetaboliteLMST04030258 (LIPID MAPS)
7α-HydroxycholesterolMetaboliteLMST01010013 (LIPID MAPS) AKA 7α-hydroxycholesterol (7α-HC)
7α−Hydroxycholest -4-en-3-oneMetaboliteCHEBI:17899 (ChEBI)
  • aka 7α-hydroxycholest-4-en-3-one
  • "7α−HCO is a ligand to the pregnane X receptor (PXR), a member of the nuclear receptor superfamily" [PMID:31698146]
7α−Hydroxycholest -4-en-3-oneMetaboliteLMST04030123 (LIPID MAPS) aka 7α-hydroxycholest-4-en-3-one
7β,(25R)26-DihydroxycholesterolMetaboliteLMST04030178 (LIPID MAPS) AKA 7β,26-dihydroxycholesterol (7β,26-diHC).
7β-HydroxycholesterolMetaboliteLMST01010047 (LIPID MAPS) AKA 7β-hydroxycholesterol (7β-HC)
ACOT11ProteinQ8WXI4 (Uniprot-TrEMBL)
ACOT12ProteinQ8WYK0 (Uniprot-TrEMBL)
ACOT13ProteinQ9NPJ3 (Uniprot-TrEMBL)
ACOT15ProteinQ8N1Q8 (Uniprot-TrEMBL)
ACOT1ProteinQ86TX2 (Uniprot-TrEMBL)
ACOT2ProteinP49753 (Uniprot-TrEMBL) "originally thought to be in peroxisome [PMID:10944470)], later found to be mitochondrial [PMID:16940157]" [https://www.uniprot.org/uniprot/P49753]
ACOTProtein3.1.2.2 (Enzyme Nomenclature) acyl-CoA thioesterase are a group of enzymes
ACOT4ProteinQ8N9L9 (Uniprot-TrEMBL) "Compared to mouse peroxisomal succinyl-coenzyme A thioesterase/ACOT4, the human enzyme has a broad substrate specificity overlapping the activity of three mouse acyl-coenzyme A thioesterases, providing an explanation for the unexpectedly low number of acyl-coenzyme A thioesterase genes in the human genome [PMID:16940157]" [https://www.uniprot.org/uniprot/Q8N9L9]
ACOT6ProteinQ3I5F7 (Uniprot-TrEMBL)
ACOT7LProteinQ6ZUV0 (Uniprot-TrEMBL) "Could be the product of a pseudogene. The peptide used to produce antibodies against ACOT7L matches at 85% with ACOT7 and the antibodies may not be specific to ACOT7L." [https://www.uniprot.org/uniprot/Q6ZUV0]
ACOT7ProteinO00154 (Uniprot-TrEMBL)
ACOT8ProteinO14734 (Uniprot-TrEMBL)
ACOT9ProteinQ9Y305 (Uniprot-TrEMBL)
ACOX2GeneProductACOX2 (HGNC)
AKR1C4GeneProductAKR1C4 (HGNC)
AKR1D1GeneProductAKR1D1 (HGNC)
AMACRGeneProductAMACR (HGNC)
  • alpha-methylacyl-CoA racemase
  • broadly expressed [PMID:24309898, 25409824(mouse)]
BAATGeneProductBAAT (HGNC) amino acid N-acyl transferase
BACS (SLC27A5)GeneProductSLC27A5 (HGNC)
  • Bile Acid CoA ligase (or synthetase)
  • microsomal protein mostly expressed in liver [PMID:24309898, 25409824(mouse)]
CH25HProteinO95992 (Uniprot-TrEMBL) AKA cholesterol 25-hydroxylase
CYP27A1GeneProductCYP27A1 (HGNC)
CYP27A1ProteinQ02318 (Uniprot-TrEMBL)
CYP39A1GeneProductCYP39A1 (HGNC) Mostly expressed in liver, also in brain [PMID:24309898,25409824 (mouse)]
CYP3A4GeneProductCYP3A4 (HGNC) Alternative protein to CH25H for hydroxylation
CYP3A4ProteinP08684 (Uniprot-TrEMBL) Reaction also occurs in mouse: CYP3A11
CYP46A1ProteinQ9Y6A2 (Uniprot-TrEMBL) Responsible for cholesterol homeostasis in brain [PMID:8790411]. Expressed mainly in Brain, however also small quantities in testis and ovary [PMID:24309898,25409824(mouse)].
CYP7A1ProteinP22680 (Uniprot-TrEMBL)
  • cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis.
  • "the transcript of which is almost exclusively expressed in liver" [PMID:31698146]
CYP7B1ProteinO75881 (Uniprot-TrEMBL)
CYP8B1GeneProductCYP8B1 (HGNC)
ChEHProteinP34913 (Uniprot-TrEMBL)
  • AKA cholesterol epoxide hydrolase (ChEH); EC: 3.3.2.11
  • "ChEH is a dimer of 7-dehydrocholesterol reductase (DHCR7) and 3β-hydroxysteroid-Δ8-Δ7-isomerase (D8D7I)"
Chenodeoxycholic acidMetaboliteLMST04010032 (LIPID MAPS)
Cholestane-3β, 5α,6β-triolMetaboliteLMST01010510 (LIPID MAPS)
  • AKA cholestane-3β,5α,6β-triol
  • "Biomarker for NPC1; elevated levels of cholestane-3β,5α,6β-triol in plasma from NPC1 patients." [PMID: 21048217].
CholesterolMetaboliteLMST01010001 (LIPID MAPS)
Cholic acidMetaboliteLMST04010001 (LIPID MAPS)
D8D7IProteinQ15125 (Uniprot-TrEMBL)
  • "ChEH is a dimer of 7-dehydrocholesterol reductase (DHCR7) and 3β-hydroxysteroid-Δ8-Δ7-isomerase (D8D7I)"
  • also known as the emopamyl binding protein (EBP), which is the catalytic subunit [https://en.wikipedia.org/wiki/Cholesterol-5,6-oxide_hydrolase]
DBPGeneProductDBP (HGNC) D-biofinctional protein; aka MFE2, HSD17B4
DHCR7ProteinQ9UBM7 (Uniprot-TrEMBL)
Dendrogenin AMetaboliteLMST05050025 (LIPID MAPS) AKA Dendrogenin A
EBI2ProteinP32249 (Uniprot-TrEMBL)
Estrogen receptor alphaProteinP03372 (Uniprot-TrEMBL) Expressed in vascular cells.
Estrogen receptor betaProteinQ92731 (Uniprot-TrEMBL) Expressed in vascular cells.
HSD11B1ProteinP28845 (Uniprot-TrEMBL)
HSD11B2ProteinP80365 (Uniprot-TrEMBL)
HSD3B7GeneProductHSD3B7 (HGNC)
HSD3B7ProteinQ9H2F3 (Uniprot-TrEMBL)
IL-17AProteinQ16552 (Uniprot-TrEMBL) "IL-17 familiy is essential in host defense and may play key pathogenic roles in autoimmune diseases." [PMID: 25092323]
IL-17BProteinQ9UHF5 (Uniprot-TrEMBL) "IL-17 familiy is essential in host defense and may play key pathogenic roles in autoimmune diseases." [PMID: 25092323]
IL-17CProteinQ9P0M4 (Uniprot-TrEMBL) "IL-17 familiy is essential in host defense and may play key pathogenic roles in autoimmune diseases." [PMID: 25092323]
IL-17DProteinQ8TAD2 (Uniprot-TrEMBL) "IL-17 familiy is essential in host defense and may play key pathogenic roles in autoimmune diseases." [PMID: 25092323]
IL-17EProteinQ9H293 (Uniprot-TrEMBL) "IL-17 familiy is essential in host defense and may play key pathogenic roles in autoimmune diseases." [PMID: 25092323]
IL-17FProteinQ96PD4 (Uniprot-TrEMBL) "IL-17 familiy is essential in host defense and may play key pathogenic roles in autoimmune diseases." [PMID: 25092323]
INSIGProteinO15503 (Uniprot-TrEMBL)
LBPGeneProductLBP (HGNC) L-bifunctional protein, aka MFP1, enoyl-CoA hydratase and 3-hydroxacyl CoA dehydrogenase EHHADH).
LXR-alphaProteinP13133 (Uniprot-TrEMBL)
LXR-betaProteinP55055 (Uniprot-TrEMBL)
PXRProteinO75469 (Uniprot-TrEMBL)
ROR-γt ProteinF1D8P6 (Uniprot-TrEMBL)
  • AKA RAR-related orphan receptor gamma (RORγt); consists of 2 isoforms: RORγ and RORγt. This nuclear receptor is required for generating IL-17-producing CD4(+) Th17 T cells.
  • "RORγt (also known as RORγ2) – produced from an mRNA identical to that of RORγ, except that the two 5'-most exons are replaced by an alternative exon, located downstream in the gene. This causes a different, shorter N-terminus." [https://en.wikipedia.org/wiki/RAR-related_orphan_receptor_gamma]
SCPx (SCP2)GeneProductSCP2 (HGNC)
VLCS (SLC27A2)GeneProductSLC27A2 (HGNC)
  • very-long chain acyl-CoA synthetase
  • expressed mostly in liver and kidney, and present in ER and peroxisome [PMID:24309898, 25409824(mouse)]
histamineMetaboliteQ61233 (Wikidata)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
25-Hydroxycholesterol 7α,25-Dihydroxycholesterolmim-conversion24309 (Rhea)
7α,25-Dihydroxycholesterol7α,25-Dihydroxycholest -4-en-3-onemim-conversion47157 (Rhea)
7α-Hydroxycholesterol7α−Hydroxycholest -4-en-3-onemim-conversion11897 (Rhea) oxidation
Cholesterol(25R)26-Hydroxycholesterol mim-conversion46401 (Rhea)
Cholesterol24S-hydroxycholesterolmim-conversion22717 (Rhea)
Cholesterol25-Hydroxycholesterolmim-conversion21105 (Rhea)
Cholesterol7α-Hydroxycholesterolmim-conversion21813 (Rhea) 7α-hydroxylation
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4545"
Personal tools