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/index.php/Pathway:WP4545 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. 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) [https://dx.doi.org/10.1016%2Fj.prostaglandins.2019.106381] and will be extended with disease information. c02 aka 7-DHC abundant in SLOS. aka 7-OC Elevated levels found in Wolman's disease aka 3b,5a-Dihydroxycholestan-6-one radical Bile Acid CoA ligase (or synthetase) microsomal protein mostly expressed in liver [PMID:24309898, 25409824(mouse)] d46 very-long chain acyl-CoA synthetase expressed mostly in liver and kidney, and present in ER and peroxisome [PMID:24309898, 25409824(mouse)] d46 alpha-methylacyl-CoA racemase broadly expressed [PMID:24309898, 25409824(mouse)] d46 D-biofinctional protein; aka MFE2, HSD17B4 D-biofinctional protein; aka MFE2, HSD17B4 amino acid N-acyl transferase acyl-CoA thioesterase are a group of enzymes "originally thought to be in peroxisome [PMID:10944470)], later found to be mitochondrial [PMID:16940157]" [https://www.uniprot.org/uniprot/P49753] f07 a7b "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] a7b "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] 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)" ae1 Bile Acid CoA ligase (or synthetase) microsomal protein mostly expressed in liver [PMID:24309898, 25409824(mouse)] d46 very-long chain acyl-CoA synthetase expressed mostly in liver and kidney, and present in ER and peroxisome [PMID:24309898, 25409824(mouse)] d46 alpha-methylacyl-CoA racemase broadly expressed [PMID:24309898, 25409824(mouse)] d46 D-biofinctional protein; aka MFE2, HSD17B4 D-biofinctional protein; aka MFE2, HSD17B4 amino acid N-acyl transferase acyl-CoA thioesterase are a group of enzymes "originally thought to be in peroxisome [PMID:10944470)], later found to be mitochondrial [PMID:16940157]" [https://www.uniprot.org/uniprot/P49753] f07 a7b "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] a7b "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] radical (deoxidised) radical "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] afa "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] afa Mechanism of transport to ER and plasma membrane has yet to be established [PMID: 24664998] c07 c02 c7e c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 ec0 c02 c02 c02 c02 c02 c02 c02 c02 cb4 f2f ffa c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 c02 transport to membrane bound NPC1 Biomarker for Biomarker for Biomarker for Biomarker for Biomarker for Biomarker for AKA Smith–Lemli–Opitz syndrome d91 da6 NIEMANN-PICK DISEASE, TYPE C1 c4e NIEMANN-PICK DISEASE, TYPE B results from mutation in SMPD1 gene bbd NIEMANN-PICK DISEASE, TYPE A bbd NIEMANN-PICK DISEASE, TYPE C2 cholesterol metabolic pathway PW:0001304 Pathway Ontology classic metabolic pathway PW:0000002 Pathway Ontology Niemann-Pick disease type A DOID:0070111 Human Disease Ontology Niemann-Pick disease type B DOID:0070112 Human Disease Ontology Niemann-Pick disease type C1 DOID:0070113 Human Disease Ontology Smith-Lemli-Opitz syndrome DOID:14692 Human Disease Ontology Smith-Lemli-Opitz Syndrome pathway PW:0001650 Pathway Ontology Niemann-Pick disease type C2 DOID:0070114 Human Disease Ontology 31698146 PubMed Oxysterols as lipid mediators: Their biosynthetic genes, enzymes and metabolites. 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