Prostacyclin synthase

Prostacyclin synthase
	Ribbon model with heme in the center ( calottes ) according to PDB 2IAG
	Existing structural data : PDB 2iag , 3b6h
Properties of human protein
Mass / length primary structure	57.1 kilodaltons / 500 amino acids
Secondary to quaternary structure	single pass membrane protein
Cofactor	Heme thiolate
Identifier
Gene names	PTGIS ; CYP8A1
External IDs	OMIM : 601699 ; UniProt : Q16647 ; MGI : 1097156 ;
Enzyme classification
EC, category	5.3.99.4 , isomerase
Response type	Rearrangement
Substrate	Prostaglandin H2
Products	Prostacyclin
Occurrence
Parent taxon	Vertebrates
	Orthologue

Prostacyclin synthase ( gene : PTGIS ) is the enzyme that catalyzes the rearrangement of prostaglandin H2 to prostacyclin . This reaction is the counterweight to the conversion to thromboxane A2 , and the reaction products are also physiological counterparts. The synthase occurs in vertebrates . In humans, it is found as a membrane protein in all tissue types, but especially in the ovaries , heart , skeletal muscles , lungs and prostate .

Prostacyclin synthase is located in the membrane of the endoplasmic reticulum on the inside and is closely associated with the enzymes COX-1 / COX-2 via a fusion protein . As the antagonist of thromboxane A2-produced thrombosis , prostacyclin synthase is a gene therapeutic target for the treatment of pulmonary hypertension .

Catalyzed reaction

⇒

Prostaglandin H2 is rearranged to prostaglandin I2 (prostacyclin).

More functions

Certain prostacyclin synthase variants have been associated with severe respiratory syncytial virus infection in Japanese children.

regulation

Signal transduction by tretinoin via the retinoic acid receptor increases the expression of prostacyclin synthase. Enzyme activity is inhibited by peroxynitrite, which by glutathione or vitamin C is prevented.

Individual evidence

↑ UniProt Q16647
↑ Wu KK, Liou JY: Cellular and molecular biology of prostacyclin synthase . In: Biochem. Biophys. Res. Commun. . 338, No. 1, December 2005, pp. 45-52. doi : 10.1016 / j.bbrc.2005.08.021 . PMID 16115610 .
↑ Ruan KH, Deng H, So SP: Engineering of a protein with cyclooxygenase and prostacyclin synthase activities that converts arachidonic acid to prostacyclin . In: Biochemistry . 45, No. 47, November 2006, pp. 14003-11. doi : 10.1021 / bi0614277 . PMID 17115695 .
↑ Ito T, Okada T, Mimuro J, et al : Adenoassociated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats . In: Hypertension . 50, No. 3, September 2007, pp. 531-6. doi : 10.1161 / HYPERTENSIONAHA.107.091348 . PMID 17635855 .
↑ Hashimoto K, Ishibashi K, Gebretsadik T, et al : Functional polymorphism of the promoter region of the prostacyclin synthase gene and severity of RSV infection in hospitalized children . In: J. Med. Virol. . 80, No. 11, November 2008, pp. 2015–22. doi : 10.1002 / jmv.21318 . PMID 18814254 .
↑ Camacho M, Rodríguez C, Salazar J, et al : Retinoic acid induces PGI synthase expression in human endothelial cells . In: J. Lipid Res . 49, No. 8, August 2008, pp. 1707-14. doi : 10.1194 / jlr.M700559-JLR200 . PMID 18458045 .
↑ Zou MH: Peroxynitrite and protein tyrosine nitration of prostacyclin synthase . In: Prostaglandins Other Lipid Mediat. . 82, No. 1-4, January 2007, pp. 119-27. doi : 10.1016 / j.prostaglandins.2006.05.005 . PMID 17164139 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Arachidonic Acid Metabolism - Learning and Teaching Materials

Jassal / D'Eustachio / reactome.org: Prostacyclin synthase (CYP8A1) mediates the isomerization of prostaglandin H2 to prostaglandin I2

[1] UniProt Q16647

[2] Wu KK, Liou JY: Cellular and molecular biology of prostacyclin synthase . In: Biochem. Biophys. Res. Commun. . 338, No. 1, December 2005, pp. 45-52. doi : 10.1016 / j.bbrc.2005.08.021 . PMID 16115610 .

[3] Ruan KH, Deng H, So SP: Engineering of a protein with cyclooxygenase and prostacyclin synthase activities that converts arachidonic acid to prostacyclin . In: Biochemistry . 45, No. 47, November 2006, pp. 14003-11. doi : 10.1021 / bi0614277 . PMID 17115695 .

[4] Ito T, Okada T, Mimuro J, et al : Adenoassociated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats . In: Hypertension . 50, No. 3, September 2007, pp. 531-6. doi : 10.1161 / HYPERTENSIONAHA.107.091348 . PMID 17635855 .

[5] Hashimoto K, Ishibashi K, Gebretsadik T, et al : Functional polymorphism of the promoter region of the prostacyclin synthase gene and severity of RSV infection in hospitalized children . In: J. Med. Virol. . 80, No. 11, November 2008, pp. 2015–22. doi : 10.1002 / jmv.21318 . PMID 18814254 .

[6] Camacho M, Rodríguez C, Salazar J, et al : Retinoic acid induces PGI synthase expression in human endothelial cells . In: J. Lipid Res . 49, No. 8, August 2008, pp. 1707-14. doi : 10.1194 / jlr.M700559-JLR200 . PMID 18458045 .

[7] Zou MH: Peroxynitrite and protein tyrosine nitration of prostacyclin synthase . In: Prostaglandins Other Lipid Mediat. . 82, No. 1-4, January 2007, pp. 119-27. doi : 10.1016 / j.prostaglandins.2006.05.005 . PMID 17164139 .