Prostacyclin synthase explained

prostaglandin-I synthase
Ec Number:	5.3.99.4
Cas Number:	65802-86-0
Go Code:	0008116
Width:	292px

Prostaglandin-I synthase also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an enzyme involved in prostanoid biosynthesis that in humans is encoded by the PTGIS gene.^[1] This enzyme belongs to the family of cytochrome P450 isomerases.

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. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostaglandin H₂ to prostacyclin (prostaglandin I₂), a potent vasodilator and inhibitor of platelet aggregation. An imbalance of prostacyclin and its physiological antagonist thromboxane A₂ contribute to the development of myocardial infarction, stroke, and atherosclerosis.^[2]

Unlike most P450 enzymes, PGIS does not require molecular oxygen (O₂). Instead it uses its heme cofactor to catalyze the isomerization of prostaglandin H₂ to prostacyclin. Prostaglandin H₂ is produced by cyclooxygenase in the first committed step of prostaglandin biosynthesis.

Nomenclature

The systematic name of this enzyme class is (5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate 6-isomerase. Other names in common use include prostacyclin synthase, prostacyclin synthetase, prostagladin I₂ synthetase, PGI₂ synthase, PGIS, PTGIS, and PGI₂ synthetase.

See also

• Prostanoid

Further reading

• DeWitt DL, Smith WL . 1983 . Purification of prostacyclin synthase from bovine aorta by immunoaffinity chromatography. Evidence that the enzyme is a hemoprotein . J. Biol. Chem. . 258 . 3285 - 93 . 6338016 . 5 . 10.1016/S0021-9258(18)32859-X . free .
• Ullrich V, Castle L, Weber P . 1981 . Spectral evidence for the cytochrome P450 nature of prostacyclin synthetase . Biochem. Pharmacol. . 30 . 2033 - 6 . 7023490 . 10.1016/0006-2952(81)90218-5 . 14 .
• Xie X, Ma YT, Fu ZY, etal . [Study on the association of cyclooxygenase-2 -765g>C and prostacyclin synthase C1117A polymorphisms and the risk of myocardial infarction in Uigur population of Xinjiang, China] . Zhonghua Liu Xing Bing Xue Za Zhi . 29 . 6 . 598–603 . 2008 . 19040046 .
• Yoshida T, Kato K, Yokoi K, etal . Association of genetic variants with chronic kidney disease in individuals with different lipid profiles. . Int. J. Mol. Med. . 24 . 2 . 233–46 . 2009 . 19578796 . 10.3892/ijmm_00000226. free .
• Palmieri RT, Wilson MA, Iversen ES, etal . Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women. . Cancer Epidemiol. Biomarkers Prev. . 17 . 12 . 3567–72 . 2008 . 19064572 . 10.1158/1055-9965.EPI-08-0548 . 2664299 .
• Mavaddat N, Dunning AM, Ponder BA, etal . Common genetic variation in candidate genes and susceptibility to subtypes of breast cancer. . Cancer Epidemiol. Biomarkers Prev. . 18 . 1 . 255–9 . 2009 . 19124506 . 10.1158/1055-9965.EPI-08-0704 . 2655077 .
• Xie X, Ma YT, Fu ZY, etal . [Association of GLu461ALa polymorphism of prostacyclin synthase gene with myocardial infarction in Uigur population] . Zhonghua Yu Fang Yi Xue Za Zhi . 43 . 3 . 237–41 . 2009 . 19534932 .
• Yoshida T, Kato K, Fujimaki T, etal . Association of a polymorphism of the apolipoprotein E gene with chronic kidney disease in Japanese individuals with metabolic syndrome. . Genomics . 93 . 3 . 221–6 . 2009 . 19056482 . 10.1016/j.ygeno.2008.11.001 . free .
• Dagle JM, Lepp NT, Cooper ME, etal . Determination of genetic predisposition to patent ductus arteriosus in preterm infants. . Pediatrics . 123 . 4 . 1116–23 . 2009 . 19336370 . 10.1542/peds.2008-0313 . 2734952 .
• Xie X, Ma Y, Fu Z, etal . [Association of polymorphism of the prostacyclin synthase gene with myocardial infarction in Uigur population of Xinjiang] . Zhonghua Yi Xue Yi Chuan Xue Za Zhi . 25 . 6 . 708–11 . 2008 . 19065539 .
• Nelson DR, Zeldin DC, Hoffman SM, etal . Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. . Pharmacogenetics . 14 . 1 . 1–18 . 2004 . 15128046 . 10.1097/00008571-200401000-00001 .
• Barbali M, Naranci NS, Skari-Juri T. A quantitative trait locus for SBP maps near KCNB1 and PTGIS in a population isolate. . Am. J. Hypertens. . 22 . 6 . 663–8 . 2009 . 19265782 . 10.1038/ajh.2009.46 . etal. free .
• Xie X, Ma YT, Fu ZY, etal . Association of polymorphisms of PTGS2 and CYP8A1 with myocardial infarction. . Clin. Chem. Lab. Med. . 47 . 3 . 347–52 . 2009 . 19327107 . 10.1515/CCLM.2009.078 . 30117064 .
• Abraham JE, Harrington P, Driver KE, etal . Common polymorphisms in the prostaglandin pathway genes and their association with breast cancer susceptibility and survival. . Clin. Cancer Res. . 15 . 6 . 2181–91 . 2009 . 19276290 . 10.1158/1078-0432.CCR-08-0716 . free .
• Ruan KH, Wu J, Cervantes V . Characterization of the substrate mimic bound to engineered prostacyclin synthase in solution using high-resolution NMR spectroscopy and mutagenesis: implication of the molecular mechanism in biosynthesis of prostacyclin. . Biochemistry . 47 . 2 . 680–8 . 2008 . 18081314 . 10.1021/bi701671q .
• Hashimoto K, Ishibashi K, Gebretsadik T, etal . Functional polymorphism of the promoter region of the prostacyclin synthase gene and severity of RSV infection in hospitalized children. . J. Med. Virol. . 80 . 11 . 2015–22 . 2008 . 18814254 . 10.1002/jmv.21318 . 6010576 .
• Xiang Xie . Ma YT . Fu ZY . Haplotype analysis of the CYP8A1 gene associated with myocardial infarction. . Clin. Appl. Thromb. Hemost. . 15 . 5 . 574–80 . 2009 . 19147528 . 10.1177/1076029608329581 . 20352085 . etal. free .
• Lemaitre RN, Rice K, Marciante K, etal . Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke. . Atherosclerosis . 204 . 2 . e58–63 . 2009 . 19046748 . 10.1016/j.atherosclerosis.2008.10.011 . 2753183 .
• Ito T, Okada T, Mimuro J, etal . Adenoassociated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats. . Hypertension . 50 . 3 . 531–6 . 2007 . 17635855 . 10.1161/HYPERTENSIONAHA.107.091348 . free .
• Ma YT, Xie X, Fu ZY, etal . [Haplotypes analysis of the prostacyclin synthase gene and myocardial infarction in Uigur population] . Zhonghua Xin Xue Guan Bing Za Zhi . 37 . 2 . 115–9 . 2009 . 19719985 .
• Yeh HC, Gerfen GJ, Wang JS, etal . Characterization of the peroxidase mechanism upon reaction of prostacyclin synthase with peracetic acid. Identification of a tyrosyl radical intermediate. . Biochemistry . 48 . 5 . 917–28 . 2009 . 19187034 . 10.1021/bi801382v . 2849756 .
• Young RP, Hopkins RJ, Hay BA, etal . A gene-based risk score for lung cancer susceptibility in smokers and ex-smokers. . Postgrad Med J . 85 . 1008 . 515–24 . 2009 . 19789190 . 10.1136/pgmj.2008.077107 . free .

Notes and References

1. Yokoyama C, Yabuki T, Inoue H, Tone Y, Hara S, Hatae T, Nagata M, Takahashi EI, Tanabe T . Human gene encoding prostacyclin synthase (PTGIS): genomic organization, chromosomal localization, and promoter activity . Genomics . 36 . 2 . 296–304 . September 1996 . 8812456 . 10.1006/geno.1996.0465 .
2. Web site: Entrez Gene: PTGIS .