PathwayStep1909 PathwayStep1900 PathwayStep1902 PathwayStep1901 PathwayStep1904 PathwayStep1903 PathwayStep1906 PathwayStep1905 PathwayStep1908 PathwayStep1907 PathwayStep1912 PathwayStep1910 PathwayStep1911 PathwayStep1897 PathwayStep1898 PathwayStep1899 PathwayStep1893 PathwayStep1894 PathwayStep1895 PathwayStep1896 PathwayStep1892 PathwayStep1891 PathwayStep1890 PathwayStep1884 PathwayStep1885 PathwayStep1882 PathwayStep1883 PathwayStep1888 PathwayStep1889 PathwayStep1886 PathwayStep1887 PathwayStep1881 TXB2 is converted to 11dh-TXB2 by TXDH PGH2 is degraded to 12S-HHT and MDA by TBXAS1 TXA2 is hydrolysed to TXB2 PGH2 is isomerised to PGD2 by PTGDS PGA2 is dehydrated to 15d-PGA2 PGH2 is isomerised to PGD2 by HPGDS PGH2 is reduced to PGF2a by FAM213B PGH2 is isomerised to PGE2 by PTGES Prostaglandin E synthase isomerizes PGH2 to PGE2 PGE2 is converted to PGF2a by CBR1 PGE2 is dehydrated to PGA2 PGA2 is isomerised to PGC2 PGC2 is isomerised to PGB2 PGH2 is isomerised to TXA2 by TBXAS1 PGI2 is hydrolysed to 6k-PGF1a Delta12-PGJ2 is dehydrated to 15d-PGJ2 PGD2 is dehydrated to 15d-PGD2 PGD2 is dehydrated to PGJ2 PGJ2 is isomerised to delta12-PGJ2 15k-PGE2/F2a is reduced to dhk-PGE2/F2a by PTGR1 PGH2 is isomerised to PGI2 by PTGIS PGD2 is reduced to 11-epi-PGF2a by AKRIC3 PGD2/E2/F2a is oxidised to 15k-PGD2/E2/F2a by HPGD PGH2 diffuses from the endoplasmic reticulum lumen to the cytosol PGH2 is reduced to PGF2a by AKR1C3 PGG2 is reduced to PGH2 by PTGS1 PGG2 is reduced to PGH2 by PTGS2 Arachidonic acid oxidised to PGG2 Arachidonic acid oxidised to PGG2 Aspirin acetylates PTGS2 Aspirin acetylates PTGS1 PTGS2 dimer binds celecoxib Synthesis of Prostaglandins (PG) and Thromboxanes (TX) Authored: Williams, MG, 2012-02-24 Edited: Williams, MG, 2012-02-24 GENE ONTOLOGYGO:0019371 ISBN978-0-444-53219-0 Pubmed19244215 Pubmed20655950 Reactome Database ID Release 432162123 Reactome, http://www.reactome.org ReactomeREACT_150149 Reviewed: Rush, MG, 2012-11-10 The bioactive prostaglandin (PG) signalling molecules, including PGA2, PGE2, PGF2a, and PGI2 (prostacyclin) are synthesised from arachidonic acid and its products by various prostaglandin synthase type enzymes. Prostaglandin H2 (PGH2) is the starting point for the synthesis of Thromboxanes (TXs) (Buczynski et al. 2009, Vance & Vance 2008). PGs and TXs are collectively known as the prostanoids.<br>Two enzymes, PTGS1 and 2 (COX1 and 2) both catalyze the two-step conversion of arachidonic acid to PGH2. PTGS1 is constitutively expressed in many cell types while PTGS2 is induced in response to stress and mediates the syntheses of prostaglandins associated with pain, fever, and inflammation. Aspirin irreversibly inactivates both enzymes (though it acts more efficiently on PTGS1), explaining both its antiinflammatory effects and side effects like perturbed gastic acid secretion. Drugs like celecoxib, by specifically inhibiting PTGS2, have a strong anti-inflammatory effect with fewer side effects. These PTGS2-specific drugs, however, probably because of their effects on the balance of prostaglandin synthesis in platelets and endothelial cells, can also promote blood clot formation (Buczynski et al. 2009; Stables & Gilroy 2011).