CYP2C18 explained

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.

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]}

Further reading

• Goldstein JA, de Morais SM . Biochemistry and molecular biology of the human CYP2C subfamily . Pharmacogenetics . 4 . 6 . 285–99 . December 1994 . 7704034 . 10.1097/00008571-199412000-00001 .
• Smith G, Stubbins MJ, Harries LW, Wolf CR . Molecular genetics of the human cytochrome P450 monooxygenase superfamily . Xenobiotica . 28 . 12 . 1129–65 . December 1998 . 9890157 . 10.1080/004982598238868 .
• Ged C, Beaune P . Partial sequence and polymerase chain reaction-mediated analysis of expression of the human CYP2C18 gene . Pharmacogenetics . 2 . 3 . 109–15 . June 1992 . 1306110 . 10.1097/00008571-199206000-00002 .
• Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA . Cloning and expression of complementary DNAs for multiple members of the human cytochrome PH50IIC subfamily . Biochemistry . 32 . 5 . 1390 . February 1993 . 8095407 . 10.1021/bi00056a025 .
• Goldstein JA, Faletto MB, Romkes-Sparks M, Sullivan T, Kitareewan S, Raucy JL, Lasker JM, Ghanayem BI . Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humans . Biochemistry . 33 . 7 . 1743–52 . February 1994 . 8110777 . 10.1021/bi00173a017 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• de Morais SM, Schweikl H, Blaisdell J, Goldstein JA . Gene structure and upstream regulatory regions of human CYP2C9 and CYP2C18 . Biochemical and Biophysical Research Communications . 194 . 1 . 194–201 . July 1993 . 8333835 . 10.1006/bbrc.1993.1803 .
• Richardson TH, Griffin KJ, Jung F, Raucy JL, Johnson EF . 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 . 9028867 . 10.1006/abbi.1996.9817 .
• Zaphiropoulos PG . 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 . 9154796 . 232150 . 10.1128/mcb.17.6.2985.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Macé K, Bowman ED, Vautravers P, Shields PG, Harris CC, Pfeifer AM . Characterisation of xenobiotic-metabolising enzyme expression in human bronchial mucosa and peripheral lung tissues . European Journal of Cancer . 34 . 6 . 914–20 . May 1998 . 9797707 . 10.1016/S0959-8049(98)00034-3 .
• Klose TS, Blaisdell JA, Goldstein JA . Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs . Journal of Biochemical and Molecular Toxicology . 13 . 6 . 289–95 . 1999 . 10487415 . 10.1002/(SICI)1099-0461(1999)13:6<289::AID-JBT1>3.0.CO;2-N . 25926848 .
• Finta C, Zaphiropoulos PG . The human CYP2C locus: a prototype for intergenic and exon repetition splicing events . Genomics . 63 . 3 . 433–8 . February 2000 . 10704292 . 10.1006/geno.1999.6063 .
• Thum T, Borlak J . Gene expression in distinct regions of the heart . Lancet . 355 . 9208 . 979–83 . March 2000 . 10768437 . 10.1016/S0140-6736(00)99016-0 . 23176414 .
• Marill J, Cresteil T, Lanotte M, Chabot GG . Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites . Molecular Pharmacology . 58 . 6 . 1341–8 . December 2000 . 11093772 . 10.1124/mol.58.6.1341.
• Zhu-Ge J, Yu YN, Qian YL, Li X . 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 . 12378636 . 10.3748/wjg.v8.i5.888. 4656581 . free .

Notes and References

1. Urs A. Meyer . Harry Gelboin . Furuya H, Meyer UA, Gelboin HV, Gonzalez FJ . Polymerase chain reaction-directed identification, cloning, and quantification of human CYP2C18 mRNA . Molecular Pharmacology . 40 . 3 . 375–82 . September 1991 . 1896026 .
2. Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA . Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily . Biochemistry . 30 . 13 . 3247–55 . April 1991 . 2009263 . 10.1021/bi00227a012 .
3. Web site: Entrez Gene: CYP2C18 cytochrome P450, family 2, subfamily C, polypeptide 18.
4. Fleming I . 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 . 25244930 . 10.1124/pr.113.007781 . free .
5. Wagner K, Vito S, Inceoglu B, Hammock BD . The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling . Prostaglandins & Other Lipid Mediators . 113-115 . 2–12 . October 2014 . 25240260 . 10.1016/j.prostaglandins.2014.09.001 . 4254344.
6. Fischer R, Konkel A, Mehling H, Blossey K, Gapelyuk A, Wessel N, von Schacky C, Dechend R, Muller DN, Rothe M, Luft FC, Weylandt K, Schunck WH . 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 . 24634501 . 10.1194/jlr.M047357 . free . 4031946.
7. Spector AA, Kim HY . 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 . 25093613 . 10.1016/j.bbalip.2014.07.020 . 4314516.