CYP2J2

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CYP2J2
Identifiers
Aliases CYP2J2, CPJ2, CYPIIJ2, cytochrome P450 family 2 subfamily J member 2
External IDs MGI: 1270148 HomoloGene: 68091 GeneCards: CYP2J2
Targeted by Drug
terfenadine[1]
RNA expression pattern
PBB GE CYP2J2 205073 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000775

NM_010008

RefSeq (protein)

NP_000766

NP_034138.3
NP_034138

Location (UCSC) Chr 1: 59.89 – 59.93 Mb Chr 4: 96.52 – 96.55 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Cytochrome P450 2J2 (CYP2J2) is a protein that in humans is encoded by the CYP2J2 gene.[4][5] CYP2J2 is a member of the cytochrome P450 superfamily of enzymes. The enzymes are oxygenases which catalyze many reactions involved in the metabolism of drugs and other xenobiotics) as well as in the synthesis of cholesterol, steroids and other lipids.

Function[edit]

CYP2J2 localizes to the endoplasmic reticulum and is thought to be a prominent enzyme responsible for metabolizing endogenous polyunsaturated fatty acids to signaling molecules.[6] It metabolizes arachidonic acid to the following eicosatrienoic acid epoxides (termed EETs): 5,6-epoxy-8Z,11Z,14Z-EET, 5,6-epoxy-8Z,11Z,14Z-EET, 11,12-epoxy-5Z,8Z,14Z-EET, and 14,15-epoxy-5Z,8Z,11Z-EET. CYP2J2 also metabolizes linoleic acid to 9,10-epoxy octadecaenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecaenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); docosahexaenoic acid to various epoxydocosapentaenoic acids (also termed EDPs); and eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed EEQs).[7]

CYP2J2, along with CYP219, CYP2C8, CYP2C9, and possibly CYP2S1 are the main producers of EETs and, very likely EEQs, EDPs, and the epoxides of linoleic acid.[8][9]

Animal studies[edit]

Animal model studies implicate The EETs, EDPs, and EEQs in regulating hypertension, the development of Myocardial infarction and other damages to the heart, the growth of various cancers, inflammation, blood vessel formation, and pain perception; limited studies suggest but have not proven that these epoxides may function similarly in humans (see epoxyeicosatrienoic acid, epoxydocosapentaenoic acid, and epoxygenase pages).[9] Vernolic and coronaric acids are potentially toxic, causing multiple organ failure and respiratory distress when injected into animals.[9]

References[edit]

  1. ^ "Drugs that physically interact with Cytochrome P450 family 2 subfamily J member 2 view/edit references on wikidata". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ Ma J, Ramachandran S, Fiedorek FT, Zeldin DC (Apr 1998). "Mapping of the CYP2J cytochrome P450 genes to human chromosome 1 and mouse chromosome 4". Genomics. 49 (1): 152–5. doi:10.1006/geno.1998.5235. PMID 9570962. 
  5. ^ "Entrez Gene: CYP2J2 cytochrome P450, family 2, subfamily J, polypeptide 2". 
  6. ^ Chen C, Wang DW (2013). "CYP epoxygenase derived EETs: from cardiovascular protection to human cancer therapy". Current Topics in Medicinal Chemistry. 13 (12): 1454–69. doi:10.2174/1568026611313120007. PMID 23688135. 
  7. ^ Westphal C, Konkel A, Schunck WH (2011). "CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?". Prostaglandins & Other Lipid Mediators. 96 (1-4): 99–108. doi:10.1016/j.prostaglandins.2011.09.001. PMID 21945326. 
  8. ^ Wagner K, Vito S, Inceoglu B, Hammock BD (2014). "The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling". Prostaglandins & Other Lipid Mediators. 113-115: 2–12. doi:10.1016/j.prostaglandins.2014.09.001. PMC 4254344Freely accessible. PMID 25240260. 
  9. ^ a b c Spector AA, Kim HY (2015). "Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism". Biochimica et Biophysica Acta. 1851 (4): 356–65. doi:10.1016/j.bbalip.2014.07.020. PMC 4314516Freely accessible. PMID 25093613. 

Further reading[edit]

  • Scarborough PE, Ma J, Qu W, Zeldin DC (Feb 1999). "P450 subfamily CYP2J and their role in the bioactivation of arachidonic acid in extrahepatic tissues". Drug Metabolism Reviews. 31 (1): 205–34. doi:10.1081/DMR-100101915. PMID 10065373. 
  • Capdevila JH, Falck JR, Harris RC (Feb 2000). "Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase". Journal of Lipid Research. 41 (2): 163–81. PMID 10681399. 
  • Wu S, Moomaw CR, Tomer KB, Falck JR, Zeldin DC (Feb 1996). "Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart". The Journal of Biological Chemistry. 271 (7): 3460–8. doi:10.1074/jbc.271.7.3460. PMID 8631948. 
  • Zeldin DC, Foley J, Ma J, Boyle JE, Pascual JM, Moomaw CR, Tomer KB, Steenbergen C, Wu S (Nov 1996). "CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance". Molecular Pharmacology. 50 (5): 1111–7. PMID 8913342. 
  • Zeldin DC, Foley J, Boyle JE, Moomaw CR, Tomer KB, Parker C, Steenbergen C, Wu S (Mar 1997). "Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas". Endocrinology. 138 (3): 1338–46. doi:10.1210/en.138.3.1338. PMID 9048644. 
  • Zeldin DC, Foley J, Goldsworthy SM, Cook ME, Boyle JE, Ma J, Moomaw CR, Tomer KB, Steenbergen C, Wu S (Jun 1997). "CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance". Molecular Pharmacology. 51 (6): 931–43. PMID 9187259. 
  • Bylund J, Finnström N, Oliw EH (Jul 1999). "Gene expression of a novel cytochrome P450 of the CYP4F subfamily in human seminal vesicles". Biochemical and Biophysical Research Communications. 261 (1): 169–74. doi:10.1006/bbrc.1999.1011. PMID 10405341. 
  • Gu J, Su T, Chen Y, Zhang QY, Ding X (Jun 2000). "Expression of biotransformation enzymes in human fetal olfactory mucosa: potential roles in developmental toxicity". Toxicology and Applied Pharmacology. 165 (2): 158–62. doi:10.1006/taap.2000.8923. PMID 10828211. 
  • King LM, Ma J, Srettabunjong S, Graves J, Bradbury JA, Li L, Spiecker M, Liao JK, Mohrenweiser H, Zeldin DC (Apr 2002). "Cloning of CYP2J2 gene and identification of functional polymorphisms". Molecular Pharmacology. 61 (4): 840–52. doi:10.1124/mol.61.4.840. PMID 11901223. 
  • Matsumoto S, Hirama T, Matsubara T, Nagata K, Yamazoe Y (Nov 2002). "Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole". Drug Metabolism and Disposition. 30 (11): 1240–5. doi:10.1124/dmd.30.11.1240. PMID 12386130. 
  • Marden NY, Fiala-Beer E, Xiang SH, Murray M (Aug 2003). "Role of activator protein-1 in the down-regulation of the human CYP2J2 gene in hypoxia". The Biochemical Journal. 373 (Pt 3): 669–80. doi:10.1042/BJ20021903. PMC 1223548Freely accessible. PMID 12737630. 
  • Pucci L, Lucchesi D, Chirulli V, Penno G, Johansson I, Gervasi P, Del Prato S, Longo V (2004). "Cytochrome P450 2J2 polymorphism in healthy Caucasians and those with diabetes mellitus". American Journal of Pharmacogenomics. 3 (5): 355–8. doi:10.2165/00129785-200303050-00006. PMID 14575523. 
  • Seubert J, Yang B, Bradbury JA, Graves J, Degraff LM, Gabel S, Gooch R, Foley J, Newman J, Mao L, Rockman HA, Hammock BD, Murphy E, Zeldin DC (Sep 2004). "Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway". Circulation Research. 95 (5): 506–14. doi:10.1161/01.RES.0000139436.89654.c8. PMID 15256482. 
  • Xiao YF, Ke Q, Seubert JM, Bradbury JA, Graves J, Degraff LM, Falck JR, Krausz K, Gelboin HV, Morgan JP, Zeldin DC (Dec 2004). "Enhancement of cardiac L-type Ca2+ currents in transgenic mice with cardiac-specific overexpression of CYP2J2". Molecular Pharmacology. 66 (6): 1607–16. doi:10.1124/mol.104.004150. PMID 15361551. 
  • Spiecker M, Darius H, Hankeln T, Soufi M, Sattler AM, Schaefer JR, Node K, Börgel J, Mügge A, Lindpaintner K, Huesing A, Maisch B, Zeldin DC, Liao JK (Oct 2004). "Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2". Circulation. 110 (15): 2132–6. doi:10.1161/01.CIR.0000143832.91812.60. PMC 2633457Freely accessible. PMID 15466638.