Oxysterols derived from cholesterol (Homo sapiens)

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Peroxisomal side-chain shortening24S- and 25-Hydroxylase pathway7α-Hydroxylase pathway:neutral/classical pathwayof bile acid biosynthesis25-hydroxylase pathway26, 4717292932, 46, 50, 5647, 6147294722, 30, 50, 624735171247474740, 431247414717145947Blood-Brain-Barrier NPC1Reduction and oxidation (presumably by AKR1D1 and AKR1C4)may precede before or after 24-hydroxylation.Based on Fig. 1[PMID:31698146]SLOSHSDBCD4+ Th17 cells5431, 385, 283α,7α,12α−tri-H-5β-cholestan-(25R)26-oic acid7-beta, (25R)26-diHC7a-Hydroxy-3,24-bisoxocholest-4-en-(25R)26-oyl-CoACYP3A47a-Hydroxy-3-oxocholest-4-en-(25S)26-oyl-CoA24S-HCDBP7a-Hydroxy-3-oxocholest-4-en-(25R)26-oyl-CoACYP3A47a,24S-Dihydroxy-3-oxocholest-4-en-(25R)26-oic acidHSD3B7EBI2DDAPXR7a-Hydroxy-3-oxochol-4-en-24-oyl-taurineSCPx (SCP2)7α,12α,(25R)26-TriH-5β-COAMACRINSIGCyp3A47α(25S)26-diHCD8D7IACOT1histamineCYP8B17α,25-diHCOCYP27A13β,7α-diHCA7a-Hydroxy-3-oxochol-4-en-24-oyl-glycineVLCS (SLC27A2)AKR1C47α,25-diHCDHCR7LBP7a,24R-Dihydroxy-3-oxocholest-4-en-(25R)26-oyl-CoABAAT7a,24S-Dihydroxy-3-oxocholest-4-en-(25R)26-oyl CoAIL-17AHSD3B7AKR1D17α−HCO7a-Hydroxy-3-oxochol-4-en-24-oyl-CoAEstrogen receptor alpha7α,12α−diHCOCYP8B1BACS (SLC27A5)LXR-alphaCyp7B15β-CO-3α,7α,12α−(25R)26-tetrolEBI2HSD3B77a-Hydroxy-3-oxochol-4-en-24-oic acidCYP27A1ROR-γt AKR1D1AKR1C4ACOTCholesterol7a-Hydroxy-3-oxocholest-4,24(E)-dien-26-oyl-CoAACOX25,6-alpha-Epoxycholesterol6314714761475163176324, 47Cholestane-3-beta,5-alpha, 6-beta-triol7-beta-HC7-alpha-HC25-HC2, 19, 37, 587-alpha,25-diHC40, 43(25R)26-HC9, 477α,26-diHC17174, 13, 45, 47, 5210, 47, 525, 6, 15, 23, 47...473, 39, 47, 48Cyp27A1Cyp27A120, 44, 47Cyp7A120, 44Cyp27A14720, 44, 47Cyp7B147CH25HCyp46A147ChEH631763IL-17BIL-17CIL-17DIL-17EIL-17F29Estrogen receptor beta29LXR-betaCTX38, 42, 53SPG531, 38NP Type B8NP type A8477α−HCO477-alpha-HC477α(25S)26-diHCO47, 61477α,12α−diH-5β-CO5β-CO-3α,7α,12α−triolCyp27A120, 44, 473β-HCA47, 52Cyp27A14720, 44, 47477α(25R)26−diHCO7α-H-3-oxoC-4-en-(25R)26-oic acid47474747CYP27A1CYP27A147477α, 12α,(25R)26−triHCO47474747477α,12α,-H-3-oxoC-4-en-(25R)26-oic acid47CYP8B14747477α,12α-diH-3-oxo-5β-CO-(25R)26-oic acid4747AKR1D1CYP27A147Based on Fig. 1[PMID:31698146]CYP8B17a,12a,25-TriH-cholest-4-en-3-one7a,25-DiH-cholest-4-en-3-one7a,25-DiH-3-oxocholest-4-en-26-oic acid7a,12a-DiH-3-oxochol-4-en-24-oic acid577a,12a,25-TriH-cholest-4-en-3,24-dioneCholic acid7a,12a,24,25-TetraH-cholest-4-en-3-one7a,24S-DiHCO63HSD3B7CYP39A1637a,24S-diH,3O-CACYP27A135, 577a,24S-DiHC346, 47474724, 47474714, 474714, 4735, 4735, 47AKR1C414Based on Fig. 2[PMID:31698146]35LXR-alphaLXR-beta24S-HC32, 46, 5632, 46, 56EBI2597α-H-3-oxoC-4-en-(25R)26-oic acid4747474747474718, 33, 4747474747Based on Fig. 3[PMID:31698146]47AMACRD16, 49CBAS66018, 33, 47ACOT2ACOT411, 2711ACOT6ACOT7ACOT8ACOT9ACOT11ACOT12ACOT13ACOT7LACOT15DBPD7LKDMN55FHCA21BACS (SLC27A5)VLCS (SLC27A2)6363


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). 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) [1], 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) [2] (green boxes), Figure 2 (yellow box) and Figure 3 (blue box).

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Bibliography

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History

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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
(25R)26-HCMetaboliteQ15634124 (Wikidata)
  • "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-HCMetaboliteQ27071873 (Wikidata)
  • AKA (24S)-hydroxycholesterol
  • Can corss the Blood-Brain-Barrier (to remove cholesterol from brain tissue) [PMID:8790411; 9717719]
25-HCMetaboliteQ27071875 (Wikidata)
  • AKA 25-Hydroxycholesterol
  • Produced by macrophages [PMID: 19805370, 19502589, 23273843], in vivo [PMID: 25104388].
3α,7α,12α−tri-H-5β- cholestan-(25R)26-oic acidMetaboliteCNWPIIOQKZNXBB-WBYPBBSPSA-N (InChIKey) AKA (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oic acid
3β,7α-diHCAMetaboliteQ27154974 (Wikidata) Aka 3β,7α-dihydroxycholest-5-en-(25R)26-oic acid
3β-HCAMetaboliteWVXOMPRLWLXFAP-KQOPCUSDSA-N (InChIKey)
  • "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]
5,6-alpha-EpoxycholesterolMetaboliteQ27121609 (Wikidata) AKA 5,6α-epoxycholesterol
5β-CO-3α,7α,12α −(25R)26-tetrolMetaboliteXJZGNVBLVFOSKJ-IUFSEJPUSA-N (InChIKey) aka (25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol
5β-CO-3α,7α,12α−triolMetaboliteRIVQQZVHIVNQFH-XJZYBRFWSA-N (InChIKey) aka 5beta-cholestane-3alpha,7alpha,12alpha-triol ; trihydroxycoprostane
7-alpha,25-diHCMetaboliteQ27074018 (Wikidata)
  • AKA 7α,25-Dihydroxycholesterol
  • Involved in immune response (agonist of G-protein-coupled receptor EBI2 (AKA GPR183)) [PMID: 21796212, 21796211].
7-alpha-HCMetaboliteQ155744 (Wikidata) AKA 7α-hydroxycholesterol (7α-HC)
7-beta, (25R)26-diHCMetaboliteQ27074030 (Wikidata) AKA 7β,26-dihydroxycholesterol (7β,26-diHC).
7-beta-HCMetaboliteQ27074031 (Wikidata) AKA 7β-hydroxycholesterol (7β-HC)
7a,12a,24,25-TetraH- cholest-4-en-3-oneMetaboliteRLXAPPIBYACUSX-GYXSHVEISA-N (InChIKey) aka 7a,12a,24,25-Tetrahydroxycholest-4-en-3-one
7a,12a,25-TriH-cholest- 4-en-3,24-dioneMetaboliteRJOIOUAJASFEIW-UOQBUNJGSA-N (InChIKey) aka 7a,12a,25-Trihydroxycholest-4-en-3,24-dione
7a,12a,25-TriH-cholest- 4-en-3-oneMetaboliteFQABTKAQUPNRDK-RIOWZCLJSA-N (InChIKey) aka 7a,12a,25-Trihydroxycholest-4-en-3-one
7a,12a-DiH-3-oxochol- 4-en-24-oic acidMetaboliteZZUMXQCSMJCDDC-DFQOQHGMSA-N (InChIKey) aka 7a,12a-Dihydroxy-3-oxochol-4-en-24-oic acid
7a,24R-Dihydroxy-3-oxocholest- 4-en-(25R)26-oyl-CoAMetaboliteIPIPDCALAORYQI-RBHDQGRHSA-N (InChIKey)
7a,24S-DiHCOMetaboliteLFFHZNXDGBQZCO-GXKBHXPCSA-N (InChIKey) aka 7a,24S-Dihydroxycholest-4-en-3-one, 7a,24S-DiH-cholest-4-en-3-one
7a,24S-DiHCMetaboliteZNCHPOYZMVVJCK-LIZWOPGQSA-N (InChIKey)
  • aka 7a,24S-Dihydroxycholesterol, 7a,24S-DiH-cholesterol
  • Found in human plasma [PMID:31009661]
7a,24S-Dihydroxy-3-oxocholest- 4-en-(25R)26-oic acidMetaboliteJZZVPWQJIWZQQG-WVJJBTFRSA-N (InChIKey)
7a,24S-Dihydroxy-3-oxocholest- 4-en-(25R)26-oyl CoAMetaboliteIPIPDCALAORYQI-SZRSLPTQSA-N (InChIKey)
7a,24S-diH,3O-CAMetaboliteJZZVPWQJIWZQQG-WVJJBTFRSA-N (InChIKey)
  • aka 7a,24S-Dihydroxy-3-oxocholest-4-en-26-oic acid, 7a,24S-DiH-3-oxocholest-4-en-26-oic acid
  • Identified in human plasma [PMID:29960034] and CSF [PMID:30578919,29960034]
7a,25-DiH-3-oxocholest- 4-en-26-oic acidMetaboliteDUYGXKURNABVMD-KOGONGFSSA-N (InChIKey)
  • 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.
7a,25-DiH-cholest- 4-en-3-oneMetabolitePOUKDTOWHPHYQU-HENOKILYSA-N (InChIKey) aka 7a,25-Dihydroxycholest-4-en-3-one, 7a,25-diHCO.
7a-Hydroxy-3,24-bisoxocholest-4- en-(25R)26-oyl-CoAMetabolitePQRNIWLSPFPEFN-TVWKACKSSA-N (InChIKey)
7a-Hydroxy-3-oxochol- 4-en-24-oic acidMetaboliteCFLVYJJIZHNITM-NLXMLWGDSA-N (InChIKey)
7a-Hydroxy-3-oxochol- 4-en-24-oyl-CoAMetaboliteWTSQHJYZDLRRNB-WZRVWTAJSA-N (InChIKey)
7a-Hydroxy-3-oxochol- 4-en-24-oyl-glycineMetaboliteRJARQVHGCJUKLX-TYQSNJPPSA-N (InChIKey)
7a-Hydroxy-3-oxochol- 4-en-24-oyl-taurineMetaboliteCVXAKOHZAAGHRM-VOVGUEQVSA-N (InChIKey)
7a-Hydroxy-3-oxocholest- 4,24(E)-dien-26-oyl-CoAMetaboliteKFKKPWDBCOCTSD-APUQYHMQSA-N (InChIKey)
7a-Hydroxy-3-oxocholest-4- en-(25R)26-oyl-CoAMetaboliteAPRNTIKLHCDMEI-GOEZZTHFSA-N (InChIKey)
7a-Hydroxy-3-oxocholest-4- en-(25S)26-oyl-CoAMetaboliteAPRNTIKLHCDMEI-QBHUIGFPSA-N (InChIKey)
7α(25R)26−diHCOMetaboliteKVJVJJWIEXCECB-OICBIKJFSA-N (InChIKey) aka (25R)-7alpha,26-dihydroxycholest-4-en-3-one
7α(25S)26-diHCOMetaboliteKVJVJJWIEXCECB-VSSQKROFSA-N (InChIKey) aka 7α,(25S)26-dihydroxycholest-4-en-3-one
7α(25S)26-diHCMetaboliteRXMHNAKZMGJANZ-LQFSVREXSA-N (InChIKey) aka 7α,(25S)26-dihydroxycholesterol
7α, 12α,(25R)26−triHCOMetaboliteWOODKECARRKLJJ-MNOWUWSHSA-N (InChIKey) aka 7alpha,12alpha,(25R)26-trihydroxycholest-4-en-3-one
7α,12α,(25R)26 -TriH-5β-COMetaboliteUCVRZTRGVBWBPR-QGLFLVSTSA-N (InChIKey) aka 7α,12α,(25R)26-TriHydroxy-5β-cholestan-3-one
7α,12α,-H-3-oxoC-4- en-(25R)26-oic acidMetabolitePEIQVFBLXUEBGA-GJKGPBNHSA-N (InChIKey) aka 7-alpha,12-alpha-diHydroxy-3-oxocholest-4-en-(25R)26-oic acid (not available in Wikidata)
7α,12α-diH-3-oxo-5β-CO -(25R)26-oic acidMetaboliteIPDDUDDXZPWYCG-RSIKEQKEQTSA-N (InChIKey) aka 7α,12α-diHydroxy-3-oxo-5β-cholestan-(25R)26-oic acid
7α,12α−diH-5β-COMetaboliteHHVQPBXBALLUDF-QORHGLQKSA-N (InChIKey) aka 7alpha,12alpha-dihydroxy-5beta-cholestan-3-one
7α,12α−diHCOMetaboliteIOIZWEJGGCZDOL-RQDYSCIWSA-N (InChIKey) aka 7alpha-hydroxycholest-4-en-3-one
7α,25-diHCMetaboliteCHEBI:37623 (ChEBI)
  • aka 7α,25-dihydroxycholesterol
  • "the most potent EBI2 agonist 7α,25-dihydroxycholesterol (7α,25-diHC))" [PMID:31698146]
7α,25-diHCOMetaboliteCHEBI:81013 (ChEBI) aka 7α,25-dihydroxycholest-4-en-3-one
7α,26-diHCMetaboliteQ28487682 (Wikidata) AKA 7α,26-dihydroxycholesterol; 7-alpha, (25R)26-diHC
7α-H-3-oxoC-4-en- (25R)26-oic acidMetaboliteSATGKQGFUDXGAX-SLTBQWEQSA-N (InChIKey) aka 7-Hydroxy-3-oxocholest-4-en-(25R)26-oic acid
7α−HCOMetaboliteCHEBI: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]
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) Reduction and oxidation

(presumably by AKR1D1 and AKR1C4)

may precede before or after 24-hydroxylation.
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)
CYP39A1GeneProductCYP39A1 (HGNC) Mostly expressed in liver, also in brain [PMID:24309898,25409824 (mouse)]
CYP3A4GeneProductCYP3A4 (HGNC) Alternative protein to CH25H for hydroxylation
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)"
Cholestane-3-beta, 5-alpha, 6-beta-triolMetaboliteQ27103493 (Wikidata)
  • AKA cholestane-3β,5α,6β-triol
  • "Biomarker for NPC1; elevated levels of cholestane-3β,5α,6β-triol in plasma from NPC1 patients." [PMID: 21048217].
CholesterolMetaboliteQ43656 (Wikidata)
Cholic acidMetaboliteBHQCQFFYRZLCQQ-OELDTZBJSA-N (InChIKey)
Cyp27A1ProteinQ02318 (Uniprot-TrEMBL)
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)
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
DDAMetaboliteQ61983671 (Wikidata) AKA Dendrogenin A
DHCR7ProteinQ9UBM7 (Uniprot-TrEMBL)
  • "ChEH is a dimer of 7-dehydrocholesterol reductase (DHCR7) and 3β-hydroxysteroid-Δ8-Δ7-isomerase (D8D7I)"
  • the 3beta-hydroxysteroid delta7 reductase (DHCR7), which is the regulatory subunit. [https://en.wikipedia.org/wiki/Cholesterol-5,6-oxide_hydrolase]
EBI2ProteinP32249 (Uniprot-TrEMBL)
Estrogen receptor alphaProteinP03372 (Uniprot-TrEMBL) Expressed in vascular cells.
Estrogen receptor betaProteinQ92731 (Uniprot-TrEMBL) Expressed in vascular cells.
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-HC7-alpha,25-diHCmim-conversion24309 (Rhea)
7-alpha-HC7α−HCOmim-conversion11897 (Rhea) oxidation
7α,25-diHC7α,25-diHCOmim-conversion47157 (Rhea)
Cholesterol(25R)26-HCmim-conversion46401 (Rhea)
Cholesterol24S-HCmim-conversion22717 (Rhea)
Cholesterol25-HCmim-conversion21105 (Rhea)
Cholesterol7-alpha-HCmim-conversion21813 (Rhea) 7α-hydroxylation
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