Prostaglandin-I synthase (
EC5.3.99.4) also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an
enzyme involved in
prostanoid biosynthesis that in humans is encoded by the PTGISgene.[4] This enzyme belongs to the family of
cytochrome P450isomerases.
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.[5]
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.
Ullrich V, Castle L, Weber P (1981). "Spectral evidence for the cytochrome P450 nature of prostacyclin synthetase". Biochem. Pharmacol. 30 (14): 2033–6.
doi:
10.1016/0006-2952(81)90218-5.
PMID7023490.
Xie X, Ma YT, Fu ZY, et al. (2008). "[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.
PMID19040046.
Xie X, Ma YT, Fu ZY, et al. (2009). "[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.
PMID19534932.
Xie X, Ma Y, Fu Z, et al. (2008). "[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.
PMID19065539.
Nelson DR, Zeldin DC, Hoffman SM, et al. (2004). "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.
doi:
10.1097/00008571-200401000-00001.
PMID15128046.
Xie X, Ma YT, Fu ZY, et al. (2009). "Association of polymorphisms of PTGS2 and CYP8A1 with myocardial infarction". Clin. Chem. Lab. Med. 47 (3): 347–52.
doi:
10.1515/CCLM.2009.078.
PMID19327107.
S2CID30117064.
Ruan KH, Wu J, Cervantes V (2008). "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.
doi:
10.1021/bi701671q.
PMID18081314.
Hashimoto K, Ishibashi K, Gebretsadik T, et al. (2008). "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.
doi:
10.1002/jmv.21318.
PMID18814254.
S2CID6010576.
Ma YT, Xie X, Fu ZY, et al. (2009). "[Haplotypes analysis of the prostacyclin synthase gene and myocardial infarction in Uigur population]". Zhonghua Xin Xue Guan Bing Za Zhi. 37 (2): 115–9.
PMID19719985.
Prostaglandin-I synthase (
EC5.3.99.4) also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an
enzyme involved in
prostanoid biosynthesis that in humans is encoded by the PTGISgene.[4] This enzyme belongs to the family of
cytochrome P450isomerases.
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.[5]
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.
Ullrich V, Castle L, Weber P (1981). "Spectral evidence for the cytochrome P450 nature of prostacyclin synthetase". Biochem. Pharmacol. 30 (14): 2033–6.
doi:
10.1016/0006-2952(81)90218-5.
PMID7023490.
Xie X, Ma YT, Fu ZY, et al. (2008). "[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.
PMID19040046.
Xie X, Ma YT, Fu ZY, et al. (2009). "[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.
PMID19534932.
Xie X, Ma Y, Fu Z, et al. (2008). "[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.
PMID19065539.
Nelson DR, Zeldin DC, Hoffman SM, et al. (2004). "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.
doi:
10.1097/00008571-200401000-00001.
PMID15128046.
Xie X, Ma YT, Fu ZY, et al. (2009). "Association of polymorphisms of PTGS2 and CYP8A1 with myocardial infarction". Clin. Chem. Lab. Med. 47 (3): 347–52.
doi:
10.1515/CCLM.2009.078.
PMID19327107.
S2CID30117064.
Ruan KH, Wu J, Cervantes V (2008). "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.
doi:
10.1021/bi701671q.
PMID18081314.
Hashimoto K, Ishibashi K, Gebretsadik T, et al. (2008). "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.
doi:
10.1002/jmv.21318.
PMID18814254.
S2CID6010576.
Ma YT, Xie X, Fu ZY, et al. (2009). "[Haplotypes analysis of the prostacyclin synthase gene and myocardial infarction in Uigur population]". Zhonghua Xin Xue Guan Bing Za Zhi. 37 (2): 115–9.
PMID19719985.