7-oxo-C and 7-beta-HC pathways (Homo sapiens)

From WikiPathways

Jump to: navigation, search
84, 8108ER/Plasma membraneLate endosome/lysosome? unclearmechanismIrinotecan PW+3O23b,7b-Dihydroxychol-5-en-24-oyl-CoA3b,5a,6b-Trihydroxycholan-24-oic acid3b,7b-Dihydroxychol-5-en-24-oic acidSphingolipid metabolismCholestane-3b,5a,6b,(25R)26-tetrolSphingolipid degradation5a,6a-EpoxycholesterolHSD11B23b,24R-Dihydroxy-7-oxocholest-5-en-(25R)26-oyl-CoA7-OxocholesterolCYP7A1Cholestane-3b,5a,6b-triolDendrogenin ACholesterol3b-Hydroxy-7-oxocholest-5-en-(25R)26-oic acid7-Dehydrocholesterol3b,5a-DiH-cholestan-6-one7b-Peroxycholesterol3b,5a,6b,24R-Tetrahydroxycholestan-(25R)26-oyl-CoANPC13b,7b-Dihydroxychol-5-en-24-oyl-glycine3b-Hydroxy-7-oxochol-5-en-24-oyl-CoA3b-Hydroxy-7-oxochol-5-en-24-oyl-glycine3b-Hydroxy-7-oxochol-5-en-24-oic acid3b,5a,6b-Trihydroxycholan-24-oyl-glycine3b,7b-Dihydroxycholest-5-en-(25R)26-oic acidLOO*7b,(25R)26-Dihydroxycholesterol7b-Hydroxycholesterol(25R)26-Hydroxy-7-oxocholesterol3b,5a,6b-Trihydroxycholan-24-oyl-CoAHSD11B15alpha-specificDDA synthaseCYP27A13b,5a,6b-Trihydroxycholestan-(25R)26-oic acid8888883b,7b,24R-Trihydroxycholest-5-en-(25R)26-oyl-CoA8888888888, 158888888BACS (SLC27A5)VLCS (SLC27A2)1AMACR1ACOX21DBPSCPx (SCP2)DBPBAATACOT1ACOTACOT2ACOT42, 52ACOT6ACOT7ACOT8ACOT9ACOT11ACOT12ACOT13ACOT7LACOT15ChEH12CYP27A1BACS (SLC27A5)1VLCS (SLC27A2)1AMACRACOX21DBPSCPx (SCP2)DBPBAATACOT1ACOTACOT22, 5ACOT42ACOT6ACOT7ACOT8ACOT9ACOT11ACOT12ACOT13ACOT7LACOT153, 6, 8, 1688888888888HSD11B28HSD11B1HSD11B2HSD11B18HSD11B28LOOHLO*LOO*LOH+1O2SLOS11, 14DHCR7D8D7I99NPC113NP type BNP type A77NPC2CholesterolNPC2Cholesterol


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); see https://www.wikipathways.org/instance/WP4545, 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); described in this pathway, 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 describes Figure 4 and 5 from Griffiths et al. 2020 and was extended with disease information.

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms



View all...
  1. 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
  2. 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
  3. Mitić T, Shave S, Semjonous N, McNae I, Cobice DF, Lavery GG, Webster SP, Hadoke PW, Walker BR, Andrew R; ''11β-Hydroxysteroid dehydrogenase type 1 contributes to the balance between 7-keto- and 7-hydroxy-oxysterols in vivo.''; Biochem Pharmacol, 2013 PubMed Europe PMC Scholia
  4. Raleigh DR, Sever N, Choksi PK, Sigg MA, Hines KM, Thompson BM, Elnatan D, Jaishankar P, Bisignano P, Garcia-Gonzalo FR, Krup AL, Eberl M, Byrne EFX, Siebold C, Wong SY, Renslo AR, Grabe M, McDonald JG, Xu L, Beachy PA, Reiter JF; ''Cilia-Associated Oxysterols Activate Smoothened.''; Mol Cell, 2018 PubMed Europe PMC Scholia
  5. Jones JM, Gould SJ; ''Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase.''; Biochem Biophys Res Commun, 2000 PubMed Europe PMC Scholia
  6. Hult M, Elleby B, Shafqat N, Svensson S, Rane A, Jörnvall H, Abrahmsen L, Oppermann U; ''Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism.''; Cell Mol Life Sci, 2004 PubMed Europe PMC Scholia
  7. 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
  8. Griffiths WJ, Wang Y; ''Oxysterols as lipid mediators: Their biosynthetic genes, enzymes and metabolites.''; Prostaglandins Other Lipid Mediat, 2020 PubMed Europe PMC Scholia
  9. 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
  10. Vance JE, Karten B; ''Niemann-Pick C disease and mobilization of lysosomal cholesterol by cyclodextrin.''; J Lipid Res, 2014 PubMed Europe PMC Scholia
  11. Clayton PT; ''Disorders of bile acid synthesis.''; J Inherit Metab Dis, 2011 PubMed Europe PMC Scholia
  12. 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
  13. 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
  14. Shackleton CH; ''Role of a disordered steroid metabolome in the elucidation of sterol and steroid biosynthesis.''; Lipids, 2012 PubMed Europe PMC Scholia
  15. Shinkyo R, Xu L, Tallman KA, Cheng Q, Porter NA, Guengerich FP; ''Conversion of 7-dehydrocholesterol to 7-ketocholesterol is catalyzed by human cytochrome P450 7A1 and occurs by direct oxidation without an epoxide intermediate.''; J Biol Chem, 2011 PubMed Europe PMC Scholia
  16. Schweizer RA, Zürcher M, Balazs Z, Dick B, Odermatt A; ''Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid dehydrogenase type 1: species-specific differences between the rat, human, and hamster enzyme.''; J Biol Chem, 2004 PubMed Europe PMC Scholia


View all...
128557view04:57, 12 February 2024EweitzSoften disease color, standardize case
126486view21:05, 8 May 2023AlexanderPicofixed links in description
126191view12:56, 14 April 2023Ash iyerCorrected the omim identifier
126186view07:59, 14 April 2023Conroy lipidscotrrected wrong lmid
126182view10:59, 13 April 2023Conroy lipidsupdate lipid identifiers from inchikey to lipidmaps ids
126063view14:11, 31 March 2023DeSlUpdate description
120384view07:52, 30 November 2021EgonwMade pathways clickable
119276view09:22, 23 June 2021DeSlOntology Term : 'Niemann-Pick disease type C2' added !
119275view09:22, 23 June 2021DeSlOntology Term : 'Smith-Lemli-Opitz Syndrome pathway' added !
119274view09:21, 23 June 2021DeSlOntology Term : 'Smith-Lemli-Opitz syndrome' added !
119273view09:21, 23 June 2021DeSlOntology Term : 'Niemann-Pick disease type C1' added !
119272view09:21, 23 June 2021DeSlOntology Term : 'Niemann-Pick disease type B' added !
119271view09:21, 23 June 2021DeSlOntology Term : 'Niemann-Pick disease type A' added !
119270view09:20, 23 June 2021DeSlOntology Term : 'classic metabolic pathway' added !
119269view09:19, 23 June 2021DeSlConnected unconnected interaction
117643view11:40, 22 May 2021EweitzModified title
115617view16:33, 1 March 2021DeSladded biomarker info on 7-oxoC
115616view16:30, 1 March 2021DeSlAdded details on NPC1 and 2 transport of cholesterol
115615view16:17, 1 March 2021DeSlAdded niemann-pick diseases
115608view15:38, 1 March 2021DeSlUpdated title
115607view12:37, 1 March 2021DeSlAdded radical info for first three interactions
115606view12:24, 1 March 2021DeSlOntology Term : 'cholesterol metabolic pathway' added !
115604view12:21, 1 March 2021DeSlAdded link to WP4545 in description
115602view12:19, 1 March 2021DeSlUpdated description
115601view12:16, 1 March 2021DeSl
115592view10:59, 1 March 2021DeSlAdded proteins for conversions
115591view10:58, 1 March 2021DeSlAdded two missign metabolites from Fig. 5
115590view10:53, 1 March 2021DeSlAdded last missing metabolite ID
115589view10:49, 1 March 2021DeSlLayout changes
115588view10:43, 1 March 2021DeSlAdded ref for reversible interactions
115587view10:40, 1 March 2021DeSlAdded HSD11B1+2 interactions
115585view10:29, 1 March 2021DeSlAdded proteins to right hand side
115584view10:22, 1 March 2021DeSlAdded first set of proteins
115582view08:41, 1 March 2021DeSlNew pathway

External references


View all...
NameTypeDatabase referenceComment
(25R)26-Hydroxy-7-oxocholesterolMetaboliteLMST04030180 (LIPID MAPS)
3b,24R-Dihydroxy-7-oxocholest-5-en-(25R)26-oyl-CoAMetaboliteLMST04030262 (LIPID MAPS)
3b,5a,6b,24R-Tetrahydroxycholestan-(25R)26-oyl-CoAMetaboliteLMST04030244 (LIPID MAPS)
3b,5a,6b-Trihydroxycholan-24-oic acidMetaboliteLMST04010339 (LIPID MAPS)
3b,5a,6b-Trihydroxycholan-24-oyl-CoAMetaboliteLMST04010459 (LIPID MAPS)
3b,5a,6b-Trihydroxycholan-24-oyl-glycineMetaboliteLMST05030019 (LIPID MAPS)
3b,5a,6b-Trihydroxycholestan-(25R)26-oic acidMetaboliteLMST04030238 (LIPID MAPS)
3b,5a-DiH-cholestan-6-oneMetaboliteLMST01010126 (LIPID MAPS) aka 3b,5a-Dihydroxycholestan-6-one
3b,7b,24R-Trihydroxycholest-5-en-(25R)26-oyl-CoAMetaboliteLMST04030261 (LIPID MAPS)
3b,7b-Dihydroxychol-5-en-24-oic acidMetaboliteLMST04010218 (LIPID MAPS)
3b,7b-Dihydroxychol-5-en-24-oyl-CoAMetaboliteLMST04010460 (LIPID MAPS)
3b,7b-Dihydroxychol-5-en-24-oyl-glycineMetaboliteLMST05030017 (LIPID MAPS)
3b,7b-Dihydroxycholest-5-en-(25R)26-oic acidMetaboliteLMST04030235 (LIPID MAPS)
3b-Hydroxy-7-oxochol-5-en-24-oic acidMetaboliteLMST04010394 (LIPID MAPS)
3b-Hydroxy-7-oxochol-5-en-24-oyl-CoAMetaboliteLMST01010461 (LIPID MAPS)
3b-Hydroxy-7-oxochol-5-en-24-oyl-glycineMetaboliteLMST05030018 (LIPID MAPS)
3b-Hydroxy-7-oxocholest-5-en-(25R)26-oic acidMetaboliteLMST04030239 (LIPID MAPS)
5a,6a-EpoxycholesterolMetaboliteLMST01010011 (LIPID MAPS)
5alpha-specific DDA synthaseProtein
7-DehydrocholesterolMetaboliteLMST01010069 (LIPID MAPS)
  • aka 7-DHC
  • abundant in SLOS.
7-OxocholesterolMetaboliteLMST01010049 (LIPID MAPS)
  • aka 7-OC
  • Elevated levels found in Wolman's disease
7b,(25R)26-DihydroxycholesterolMetaboliteLMST04030178 (LIPID MAPS)
7b-HydroxycholesterolMetaboliteLMST01010047 (LIPID MAPS)
7b-PeroxycholesterolMetaboliteLMST01010459 (LIPID MAPS)
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)
  • alpha-methylacyl-CoA racemase
  • broadly expressed [PMID:24309898, 25409824(mouse)]
BAATGeneProduct570 (Entrez Gene) amino acid N-acyl transferase
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)]
CYP27A1GeneProductCYP27A1 (HGNC)
CYP7A1GeneProductCYP7A1 (HGNC)
ChEHProteinP34913 (Uniprot-TrEMBL)
  • AKA cholesterol epoxide hydrolase (ChEH); EC:
  • "ChEH is a dimer of 7-dehydrocholesterol reductase (DHCR7) and 3β-hydroxysteroid-Δ8-Δ7-isomerase (D8D7I)"
Cholestane-3b,5a,6b,(25R)26-tetrolMetaboliteLMST01010458 (LIPID MAPS)
Cholestane-3b,5a,6b-triolMetaboliteLMST01010052 (LIPID MAPS)
CholesterolMetaboliteLMST01010001 (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)
  • "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]
Dendrogenin AMetaboliteLMST05050025 (LIPID MAPS)
HSD11B1GeneProductHSD11B1 (HGNC)
HSD11B2GeneProductHSD11B2 (HGNC)
Irinotecan PWPathwayWP229 (WikiPathways)
LO*Metaboliteradical (deoxidised)
NPC1GeneProductNPC1 (HGNC)
NPC2GeneProductNPC2 (HGNC)
SCPx (SCP2)GeneProductSCP2 (HGNC)
Sphingolipid degradationPathwayWP4153 (WikiPathways)
Sphingolipid metabolismPathwayWP4725 (WikiPathways)
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)]

Annotated Interactions

No annotated interactions

Personal tools