PathwayStep1909 PathwayStep1907 PathwayStep1919 PathwayStep1916 PathwayStep1917 PathwayStep1914 PathwayStep1915 PathwayStep1913 PathwayStep1927 PathwayStep1924 PathwayStep1925 PathwayStep1926 PathwayStep1936 PathwayStep1933 PathwayStep1947 PathwayStep1941 PathwayStep1960 PathwayStep1964 PathwayStep1953 PathwayStep1956 PathwayStep1884 PathwayStep1885 PathwayStep1886 PathwayStep1887 PathwayStep1880 PathwayStep1879 LTA4 is converted to LTC4 by LTC4S ABCC1 mediates LTC4 export from the cell LTC4 is converted to LTD4 by GGT1/5 Further cleavage of LTD4 forms LTE4 5S-HpETE is dehydrated to LTA4 by ALOX5 LTA4 is hydrolyzed to LTB4 LTB4 is hydroxylated to 20oh-LTB4 by CYP4F2/4F3 ALOX5 is phosphorylated by MAPKAP2 Oxidation of arachidonic acid to 5-HpETE PGH2 is isomerised to TXA2 by TBXAS1 PGH2 is isomerised to PGI2 by PTGIS Hydrolysis of phosphatidylcholine PGG2 is reduced to PGH2 by PTGS1 PGG2 is reduced to PGH2 by PTGS2 Arachidonic acid oxidised to PGG2 Arachidonic acid oxidised to PGG2 Arachidonate diffuses across the ER membrane Arachidonic acid metabolism Authored: Williams, MG, 2012-02-24 Edited: Williams, MG, 2012-02-24 Eicosanoids, oxygenated, 20-carbon fatty acids, are autocrine and paracrine signaling molecules that modulate physiological processes including pain, fever, inflammation, blood clot formation, smooth muscle contraction and relaxation, and the release of gastric acid. Eicosanoids are synthesized in humans primarily from arachidonic acid (all-cis 5,8,11,14-eicosatetraenoic acid) that is released from membrane phospholipids. Once released, arachidonic acid is acted on by prostaglandin G/H synthases (PTGS, also known as cyclooxygenases (COX)) to form prostaglandins and thromboxanes, by arachidonate lipoxygenases (ALOX) to form leukotrienes, epoxygenases (cytochrome P450s and epoxide hydrolase) to form epoxides such as 15-eicosatetraenoic acids, and omega-hydrolases (cytochrome P450s) to form hydroxyeicosatetraenoic acids (Buczynski et al. 2009, Vance & Vance 2008).<br>Levels of free arachidonic acid in the cell are normally very low so the rate of synthesis of eicosanoids is determined primarily by the activity of phospholipase A2, which mediates phospholipid cleavage to generate free arachidonic acid. The enzymes involved in arachidonic acid metabolism are typically constitutively expressed so the subset of these enzymes expressed by a cell determines the range of eicosanoids it can synthesize.<br>Eicosanoids are unstable, undergoing conversion to inactive forms with half-times under physiological conditions of seconds or minutes. Many of these reactions appear to be spontaneous. GENE ONTOLOGYGO:0019369 ISBN978-0-444-53219-0 Pubmed19244215 Reactome Database ID Release 432142753 Reactome, http://www.reactome.org ReactomeREACT_147851 Reviewed: Rush, MG, 2012-11-10 Synthesis of Leukotrienes (LT) and Eoxins (EX) Synthesis of Prostaglandins (PG) and Thromboxanes (TX) Synthesis of 15-eicosatetraenoic acid derivatives Synthesis of 5-eicosatetraenoic acids Synthesis of Lipoxins (LX) Synthesis of 12-eicosatetraenoic acid derivatives Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) Synthesis of Hepoxilins (HX) and Trioxilins (TrX) Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)