Biology:CYP2C18
 Generic protein structure example |
Cytochrome P450 2C18 is a protein that in humans is encoded by the CYP2C18 gene.[1][2][3]
Function
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum but its specific substrate has not yet been determined. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. An additional gene, CYP2C17, was once thought to exist; however, CYP4217 is now considered an artefact based on a chimera of CYP2C18 and CYP2C19.[3]
CYP2C18 also possesses epoxygenase activity: it can attack various long-chain polyunsaturated fatty acids at their double (i.e. alkene) bonds to form epoxide products that act as signaling agents. It metabolizes: 1) arachidonic acid to various epoxyeicosatrienoic acids (also termed EETs); 2) linoleic acid to 9,10-epoxy octadecenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); 3) docosahexaenoic acid to various epoxydocosapentaenoic acids (also termed EDPs); and 4) eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed EEQs).[4][5][6]
While CYP2C19, CYP2C8, CYP2C9, CYP2J2, and possibly CYP2S1 are the main producers of EETs and, very likely EEQs, EDPs, and the epoxides of linoleic acid, CYP2C18 may contribute to the production of these metabolites in certain tissues.[5][7]
References
- ↑ "Polymerase chain reaction-directed identification, cloning, and quantification of human CYP2C18 mRNA". Molecular Pharmacology 40 (3): 375–82. September 1991. PMID 1896026.
- ↑ "Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily". Biochemistry 30 (13): 3247–55. April 1991. doi:10.1021/bi00227a012. PMID 2009263.
- ↑ 3.0 3.1 "Entrez Gene: CYP2C18 cytochrome P450, family 2, subfamily C, polypeptide 18". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1562.
- ↑ "The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease". Pharmacological Reviews 66 (4): 1106–40. October 2014. doi:10.1124/pr.113.007781. PMID 25244930.
- ↑ 5.0 5.1 "The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling". Prostaglandins & Other Lipid Mediators 113-115: 2–12. October 2014. doi:10.1016/j.prostaglandins.2014.09.001. PMID 25240260.
- ↑ "Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway". Journal of Lipid Research 55 (6): 1150–1164. March 2014. doi:10.1194/jlr.M047357. PMID 24634501.
- ↑ "Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1851 (4): 356–65. April 2015. doi:10.1016/j.bbalip.2014.07.020. PMID 25093613.
External links
- Human CYP2C18 genome location and CYP2C18 gene details page in the UCSC Genome Browser.
Further reading
- "Biochemistry and molecular biology of the human CYP2C subfamily". Pharmacogenetics 4 (6): 285–99. December 1994. doi:10.1097/00008571-199412000-00001. PMID 7704034.
- "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica 28 (12): 1129–65. December 1998. doi:10.1080/004982598238868. PMID 9890157.
- "Partial sequence and polymerase chain reaction-mediated analysis of expression of the human CYP2C18 gene". Pharmacogenetics 2 (3): 109–15. June 1992. doi:10.1097/00008571-199206000-00002. PMID 1306110.
- "Cloning and expression of complementary DNAs for multiple members of the human cytochrome PH50IIC subfamily". Biochemistry 32 (5): 1390. February 1993. doi:10.1021/bi00056a025. PMID 8095407.
- "Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humans". Biochemistry 33 (7): 1743–52. February 1994. doi:10.1021/bi00173a017. PMID 8110777.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Gene structure and upstream regulatory regions of human CYP2C9 and CYP2C18". Biochemical and Biophysical Research Communications 194 (1): 194–201. July 1993. doi:10.1006/bbrc.1993.1803. PMID 8333835. https://zenodo.org/record/1229414.
- "Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping of an inhibitory monoclonal antibody to P450 2C51". Archives of Biochemistry and Biophysics 338 (2): 157–64. February 1997. doi:10.1006/abbi.1996.9817. PMID 9028867.
- "Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis". Molecular and Cellular Biology 17 (6): 2985–93. June 1997. doi:10.1128/mcb.17.6.2985. PMID 9154796.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues". European Journal of Cancer 34 (6): 914–20. May 1998. doi:10.1016/S0959-8049(98)00034-3. PMID 9797707.
- "Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs". Journal of Biochemical and Molecular Toxicology 13 (6): 289–95. 1999. doi:10.1002/(SICI)1099-0461(1999)13:6<289::AID-JBT1>3.0.CO;2-N. PMID 10487415. https://zenodo.org/record/1235516.
- "The human CYP2C locus: a prototype for intergenic and exon repetition splicing events". Genomics 63 (3): 433–8. February 2000. doi:10.1006/geno.1999.6063. PMID 10704292.
- "Gene expression in distinct regions of the heart". Lancet 355 (9208): 979–83. March 2000. doi:10.1016/S0140-6736(00)99016-0. PMID 10768437.
- "Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites". Molecular Pharmacology 58 (6): 1341–8. December 2000. doi:10.1124/mol.58.6.1341. PMID 11093772.
- "Establishment of a transgenic cell line stably expressing human cytochrome P450 2C18 and identification of a CYP2C18 clone with exon 5 missing". World Journal of Gastroenterology 8 (5): 888–92. October 2002. doi:10.3748/wjg.v8.i5.888. PMID 12378636.
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