Arachidonic acid metabolism (Homo sapiens)
From WikiPathways
Description
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).
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.
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. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=2142753
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.
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. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=2142753
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History
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External references
DataNodes
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Annotated Interactions
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| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| 11dh-TXB2 | Arrow | REACT_150346 (Reactome)  | ||
| 11epi-PGF2a | Arrow | REACT_150443 (Reactome) | ||
| 12-oxoLTB4 | Arrow | REACT_150449 (Reactome) | ||
| 12R-HETE | Arrow | REACT_150334 (Reactome) | ||
| 12R-HpETE | REACT_150334 (Reactome) | |||
| 12S-HETE | Arrow | REACT_150391 (Reactome) | ||
| 12S-HHT | Arrow | REACT_150343 (Reactome) | ||
| 12S-HpETE | REACT_150391 (Reactome) | |||
| 15-HEDH | REACT_150245 (Reactome) | |||
| 15-oxoETE | Arrow | REACT_150245 (Reactome) | ||
| 15R-HETE | Arrow | REACT_150372 (Reactome) | ||
| 15S-HETE | Arrow | REACT_150230 (Reactome) | ||
| 15S-HETE | REACT_150245 (Reactome) | |||
| 15S-HpETE | REACT_150230 (Reactome) | |||
| 15d-PGA2 | Arrow | REACT_150290 (Reactome) | ||
| 15d-PGD2 | Arrow | REACT_150400 (Reactome) | ||
| 15d-PGJ2 | Arrow | REACT_150262 (Reactome) | ||
| 15k-LXA4 | Arrow | REACT_150285 (Reactome) | ||
| 15k-LXA4 | REACT_150208 (Reactome) | |||
| 15k-PGD2/E2/F2a | Arrow | REACT_150186 (Reactome) | ||
| 15k-PGE2/F2a | REACT_150174 (Reactome) | |||
| 16/17/18-HETE | Arrow | REACT_150287 (Reactome) | ||
| 19-HETE | Arrow | REACT_150441 (Reactome) | ||
| 2-Lysophosphatidylcholine | Arrow | REACT_15331 (Reactome) | ||
| 20-HETE | Arrow | REACT_150406 (Reactome) | ||
| 20cho-LTB4 | Arrow | REACT_150304 (Reactome) | ||
| 20cho-LTB4 | REACT_150283 (Reactome) | |||
| 20cho-LTB4 | REACT_150394 (Reactome) | |||
| 20cooh-LTB4 | Arrow | REACT_150283 (Reactome) | ||
| 20cooh-LTB4 | Arrow | REACT_150394 (Reactome) | ||
| 20oh-LTB4 | Arrow | REACT_13738 (Reactome) | ||
| 20oh-LTB4 | REACT_150304 (Reactome) | |||
| 5,6-EET | Arrow | REACT_150442 (Reactome) | ||
| 5-HEDH | REACT_150143 (Reactome) | |||
| 5-oxoETE | Arrow | REACT_150143 (Reactome) | ||
| 5S-HETE | Arrow | REACT_150133 (Reactome) | ||
| 5S-HETE | REACT_150143 (Reactome) | |||
| 5S-HpETE | REACT_150133 (Reactome) | |||
| 8,9/11,12/14,15-EET | Arrow | REACT_150190 (Reactome) | ||
| ABCC1 | REACT_15474 (Reactome) | |||
| AKR1C3 | REACT_150241 (Reactome) | |||
| AKR1C3 | REACT_150443 (Reactome) | |||
| ALDH | REACT_150283 (Reactome) | |||
| ALOX12 Fe2+ | REACT_150129 (Reactome) | |||
| ALOX12 Fe2+ | REACT_150303 (Reactome) | |||
| ALOX12 Fe2+ | REACT_150327 (Reactome) | |||
| ALOX12/15 | REACT_150433 (Reactome) | |||
| ALOX12B Fe2+ | REACT_150226 (Reactome) | |||
| ALOX15 Fe2+ | REACT_150189 (Reactome) | |||
| ALOX15/15B | REACT_150130 (Reactome) | |||
| ALOX5
ALOX5AP LTC4S | REACT_150156 (Reactome) | |||
| ALOX5
ALOX5AP LTC4S | REACT_150272 (Reactome) | |||
| ALOX5
ALOX5AP LTC4S | REACT_150273 (Reactome) | |||
| ALOX5
ALOX5AP LTC4S | REACT_15337 (Reactome) | |||
| ALOX5
ALOX5AP LTC4S | REACT_15413 (Reactome) | |||
| ALOX5
ALOX5AP LTC4S | REACT_15453 (Reactome) | |||
| Ac-PTGS1 dimer | Arrow | REACT_150159 (Reactome) | ||
| Ac-PTGS2 dimer | Arrow | REACT_150446 (Reactome) | ||
| Ac-PTGS2 dimer | REACT_150372 (Reactome) | |||
| Active PLA2 phosphatidylcholine | REACT_15331 (Reactome) | |||
| Arachidonic acid | Arrow | REACT_15331 (Reactome) | ||
| Arachidonic acid | REACT_147758 (Reactome) | |||
| Arachidonic acid | REACT_150129 (Reactome) | |||
| Arachidonic acid | REACT_150130 (Reactome) | |||
| Arachidonic acid | REACT_150190 (Reactome) | |||
| Arachidonic acid | REACT_150226 (Reactome) | |||
| Arachidonic acid | REACT_150287 (Reactome) | |||
| Arachidonic acid | REACT_150372 (Reactome) | |||
| Arachidonic acid | REACT_150406 (Reactome) | |||
| Arachidonic acid | REACT_150433 (Reactome) | |||
| Arachidonic acid | REACT_150441 (Reactome) | |||
| Arachidonic acid | REACT_150442 (Reactome) | |||
| Arachidonic acid | REACT_15337 (Reactome) | |||
| Arachidonic acid | REACT_528 (Reactome) | |||
| CBR1 | REACT_150185 (Reactome) | |||
| CYP | REACT_150190 (Reactome) | |||
| CYP | REACT_150287 (Reactome) | |||
| CYP | REACT_150406 (Reactome) | |||
| CYP | REACT_150441 (Reactome) | |||
| CYP | REACT_150442 (Reactome) | |||
| Cytochrome P450 | REACT_13738 (Reactome) | |||
| Cytochrome P450 | REACT_150304 (Reactome) | |||
| Cytochrome P450 | REACT_150394 (Reactome) | |||
| DPEP1/2 | REACT_15395 (Reactome) | |||
| DPEP | REACT_150428 (Reactome) | |||
| EET | REACT_150274 (Reactome) | |||
| EPHX2 dimer | REACT_150274 (Reactome) | |||
| EXA4 | REACT_150273 (Reactome) | |||
| EXD4 | Arrow | REACT_150192 (Reactome) | ||
| EXD4 | REACT_150428 (Reactome) | |||
| EXE4 | Arrow | REACT_150428 (Reactome) | ||
| FAM213B | REACT_150194 (Reactome) | |||
| GGT1/5 dimer | REACT_15356 (Reactome) | |||
| GGT | REACT_150192 (Reactome) | |||
| GPX1/2/4 | REACT_150133 (Reactome) | |||
| GPX1/2/4 | REACT_150230 (Reactome) | |||
| GPX1/2/4 | REACT_150334 (Reactome) | |||
| GPX1/2/4 | REACT_150391 (Reactome) | |||
| GSH | REACT_150133 (Reactome) | |||
| GSH | REACT_150230 (Reactome) | |||
| GSH | REACT_150273 (Reactome) | |||
| GSH | REACT_150334 (Reactome) | |||
| GSH | REACT_150391 (Reactome) | |||
| GSH | REACT_15413 (Reactome) | |||
| GSSG | Arrow | REACT_150133 (Reactome) | ||
| GSSG | Arrow | REACT_150230 (Reactome) | ||
| GSSG | Arrow | REACT_150334 (Reactome) | ||
| GSSG | Arrow | REACT_150391 (Reactome) | ||
| Glu | Arrow | REACT_15356 (Reactome) | ||
| Gly | Arrow | REACT_150428 (Reactome) | ||
| Gly | Arrow | REACT_15395 (Reactome) | ||
| H+ | Arrow | REACT_150143 (Reactome) | ||
| H+ | Arrow | REACT_150186 (Reactome) | ||
| H+ | Arrow | REACT_150245 (Reactome) | ||
| H+ | Arrow | REACT_150285 (Reactome) | ||
| H+ | Arrow | REACT_150346 (Reactome) | ||
| H+ | Arrow | REACT_150449 (Reactome) | ||
| H+ | REACT_13738 (Reactome) | |||
| H+ | REACT_147811 (Reactome) | |||
| H+ | REACT_150174 (Reactome) | |||
| H+ | REACT_150185 (Reactome) | |||
| H+ | REACT_150190 (Reactome) | |||
| H+ | REACT_150208 (Reactome) | |||
| H+ | REACT_150241 (Reactome) | |||
| H+ | REACT_150283 (Reactome) | |||
| H+ | REACT_150287 (Reactome) | |||
| H+ | REACT_150304 (Reactome) | |||
| H+ | REACT_150372 (Reactome) | |||
| H+ | REACT_150394 (Reactome) | |||
| H+ | REACT_150406 (Reactome) | |||
| H+ | REACT_150441 (Reactome) | |||
| H+ | REACT_150442 (Reactome) | |||
| H+ | REACT_150443 (Reactome) | |||
| H+ | REACT_810 (Reactome) | |||
| H2O | Arrow | REACT_13738 (Reactome) | ||
| H2O | Arrow | REACT_147811 (Reactome) | ||
| H2O | Arrow | REACT_150133 (Reactome) | ||
| H2O | Arrow | REACT_150141 (Reactome) | ||
| H2O | Arrow | REACT_150190 (Reactome) | ||
| H2O | Arrow | REACT_150230 (Reactome) | ||
| H2O | Arrow | REACT_150262 (Reactome) | ||
| H2O | Arrow | REACT_150283 (Reactome) | ||
| H2O | Arrow | REACT_150287 (Reactome) | ||
| H2O | Arrow | REACT_150290 (Reactome) | ||
| H2O | Arrow | REACT_150304 (Reactome) | ||
| H2O | Arrow | REACT_150333 (Reactome) | ||
| H2O | Arrow | REACT_150334 (Reactome) | ||
| H2O | Arrow | REACT_150372 (Reactome) | ||
| H2O | Arrow | REACT_150391 (Reactome) | ||
| H2O | Arrow | REACT_150394 (Reactome) | ||
| H2O | Arrow | REACT_150400 (Reactome) | ||
| H2O | Arrow | REACT_150406 (Reactome) | ||
| H2O | Arrow | REACT_150441 (Reactome) | ||
| H2O | Arrow | REACT_150442 (Reactome) | ||
| H2O | Arrow | REACT_15453 (Reactome) | ||
| H2O | Arrow | REACT_810 (Reactome) | ||
| H2O | REACT_150142 (Reactome) | |||
| H2O | REACT_150183 (Reactome) | |||
| H2O | REACT_150274 (Reactome) | |||
| H2O | REACT_150426 (Reactome) | |||
| H2O | REACT_150428 (Reactome) | |||
| H2O | REACT_150455 (Reactome) | |||
| H2O | REACT_15331 (Reactome) | |||
| H2O | REACT_15395 (Reactome) | |||
| H2O | REACT_15478 (Reactome) | |||
| HPGD dimer | REACT_150186 (Reactome) | |||
| HPGD dimer | REACT_150285 (Reactome) | |||
| HPGDS dimer | REACT_150171 (Reactome) | |||
| HXA3/B3 | REACT_150426 (Reactome) | |||
| HXEH | REACT_150426 (Reactome) | |||
| L-Glu | Arrow | REACT_150192 (Reactome) | ||
| LTA4 | Arrow | REACT_15453 (Reactome) | ||
| LTA4H Zn2+ | REACT_15478 (Reactome) | |||
| LTA4 | REACT_150455 (Reactome) | |||
| LTA4 | REACT_15413 (Reactome) | |||
| LTA4 | REACT_15478 (Reactome) | |||
| LTB4 | REACT_13738 (Reactome) | |||
| LTB4 | REACT_150449 (Reactome) | |||
| LTD4 | Arrow | REACT_15356 (Reactome) | ||
| LTD4 | REACT_15395 (Reactome) | |||
| LTE4 | Arrow | REACT_15395 (Reactome) | ||
| LXA4 | REACT_150285 (Reactome) | |||
| MDA | Arrow | REACT_150343 (Reactome) | ||
| NAD+ | REACT_150186 (Reactome) | |||
| NAD+ | REACT_150285 (Reactome) | |||
| NAD+ | REACT_150346 (Reactome) | |||
| NAD | Arrow | REACT_150245 (Reactome) | ||
| NADH | Arrow | REACT_150186 (Reactome) | ||
| NADH | Arrow | REACT_150285 (Reactome) | ||
| NADH | Arrow | REACT_150346 (Reactome) | ||
| NADP+ | Arrow | REACT_13738 (Reactome) | ||
| NADP+ | Arrow | REACT_150174 (Reactome) | ||
| NADP+ | Arrow | REACT_150185 (Reactome) | ||
| NADP+ | Arrow | REACT_150190 (Reactome) | ||
| NADP+ | Arrow | REACT_150208 (Reactome) | ||
| NADP+ | Arrow | REACT_150241 (Reactome) | ||
| NADP+ | Arrow | REACT_150283 (Reactome) | ||
| NADP+ | Arrow | REACT_150287 (Reactome) | ||
| NADP+ | Arrow | REACT_150304 (Reactome) | ||
| NADP+ | Arrow | REACT_150372 (Reactome) | ||
| NADP+ | Arrow | REACT_150394 (Reactome) | ||
| NADP+ | Arrow | REACT_150406 (Reactome) | ||
| NADP+ | Arrow | REACT_150441 (Reactome) | ||
| NADP+ | Arrow | REACT_150442 (Reactome) | ||
| NADP+ | Arrow | REACT_150443 (Reactome) | ||
| NADP+ | REACT_150143 (Reactome) | |||
| NADP+ | REACT_150449 (Reactome) | |||
| NADPH | Arrow | REACT_150143 (Reactome) | ||
| NADPH | Arrow | REACT_150449 (Reactome) | ||
| NADPH | REACT_13738 (Reactome) | |||
| NADPH | REACT_150174 (Reactome) | |||
| NADPH | REACT_150185 (Reactome) | |||
| NADPH | REACT_150190 (Reactome) | |||
| NADPH | REACT_150208 (Reactome) | |||
| NADPH | REACT_150241 (Reactome) | |||
| NADPH | REACT_150283 (Reactome) | |||
| NADPH | REACT_150287 (Reactome) | |||
| NADPH | REACT_150304 (Reactome) | |||
| NADPH | REACT_150372 (Reactome) | |||
| NADPH | REACT_150394 (Reactome) | |||
| NADPH | REACT_150406 (Reactome) | |||
| NADPH | REACT_150441 (Reactome) | |||
| NADPH | REACT_150442 (Reactome) | |||
| NADPH | REACT_150443 (Reactome) | |||
| NAD | REACT_150245 (Reactome) | |||
| O2 | REACT_13738 (Reactome) | |||
| O2 | REACT_147758 (Reactome) | |||
| O2 | REACT_150129 (Reactome) | |||
| O2 | REACT_150130 (Reactome) | |||
| O2 | REACT_150190 (Reactome) | |||
| O2 | REACT_150226 (Reactome) | |||
| O2 | REACT_150283 (Reactome) | |||
| O2 | REACT_150287 (Reactome) | |||
| O2 | REACT_150304 (Reactome) | |||
| O2 | REACT_150372 (Reactome) | |||
| O2 | REACT_150394 (Reactome) | |||
| O2 | REACT_150406 (Reactome) | |||
| O2 | REACT_150433 (Reactome) | |||
| O2 | REACT_150441 (Reactome) | |||
| O2 | REACT_150442 (Reactome) | |||
| O2 | REACT_15337 (Reactome) | |||
| O2 | REACT_528 (Reactome) | |||
| PGA2 | Arrow | REACT_150333 (Reactome) | ||
| PGD2/E2/F2a | REACT_150186 (Reactome) | |||
| PGD2 | REACT_150443 (Reactome) | |||
| PGE2 | REACT_150185 (Reactome) | |||
| PGF2a | Arrow | REACT_150185 (Reactome) | ||
| PGF2a | Arrow | REACT_150194 (Reactome) | ||
| PGF2a | Arrow | REACT_150241 (Reactome) | ||
| PGG2 | REACT_147811 (Reactome) | |||
| PGG2 | REACT_810 (Reactome) | |||
| PGH2 | Arrow | REACT_147811 (Reactome) | ||
| PGH2 | Arrow | REACT_810 (Reactome) | ||
| PGH2 | REACT_150194 (Reactome) | |||
| PGH2 | REACT_150241 (Reactome) | |||
| PGI2 | REACT_150142 (Reactome) | |||
| PGJ2 | Arrow | REACT_150141 (Reactome) | ||
| PTGDS | REACT_150378 (Reactome) | |||
| PTGES trimer | REACT_150407 (Reactome) | |||
| PTGES3 | REACT_15459 (Reactome) | |||
| PTGIS | REACT_1841 (Reactome) | |||
| PTGR1 | REACT_150174 (Reactome) | |||
| PTGR1 | REACT_150208 (Reactome) | |||
| PTGR1 | REACT_150449 (Reactome) | |||
| PTGS1 dimer | REACT_150159 (Reactome) | |||
| PTGS1 dimer | REACT_528 (Reactome) | |||
| PTGS1 dimer | REACT_810 (Reactome) | |||
| PTGS2 dimer | REACT_147758 (Reactome) | |||
| PTGS2 dimer | REACT_147811 (Reactome) | |||
| PTGS2 dimer | REACT_150255 (Reactome) | |||
| PTGS2 dimer | REACT_150446 (Reactome) | |||
| Phosphatidylcholine | REACT_15331 (Reactome) | |||
| REACT_13738 (Reactome) | Leukotriene B4 (LTB4) is formed from arachidonic acid and is a potent inflammatory mediator. LTB4's activity is terminated by formation of its omega hydroxylated metabolite, 20-hydroxyleukotriene B4 (20oh-LTB4), catalysed by CYP4F2 primarily in human liver (Jin et al. 1998) and also by CYP4F3 (Kikuta et al. 1998). | |||
| REACT_1377 (Reactome) | Thromboxane synthase (TBXAS1) aka CYP5A1 mediates the isomerization of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2) (Miyata et al. 2001, Chevalier et al. 2001). This reaction is not coupled with any P450 reductase proteins nor consumes NADPH. | |||
| REACT_147758 (Reactome) | Prostaglandin G/H synthase PTGS2 exhibits a dual catalytic activity, a cyclooxygenase and a peroxidase. The cyclooxygenase function catalyzes the initial conversion of arachidonic acid to an intermediate, prostaglandin G2 (PGG2) (Hamberg et al. 1974, Nugteren 1973). | |||
| REACT_147811 (Reactome) | Prostaglandin G/H synthase 2 (PTGS2) exhibits a dual catalytic activity, a cyclooxygenase and a peroxidase. The peroxidase function converts prostaglandin G2 (PGG2) to prostaglandin H2 (PGH2) via a two-electron reduction (Hamberg et al. 1973, Hla & Neilson 1992, Swinney et al. 1997, Barnett et al. 1994). | |||
| REACT_150129 (Reactome) | Arachidonate 12-lipoxygenase, 12S-type (ALOX12) converts arachidonic acid to both hepoxilin A3 (HXA3) and B3 (HXB3). They both incorporate an epoxide across the C-11 and C-12 double bond, as well as an additional hydroxyl moiety with HXA3 having a C-8 hydroxyl, whereas the HXB3 hydroxyl occurs at C-10 (Sutherland et al. 2001, Nigam et al. 2004). | |||
| REACT_150130 (Reactome) | Arachidonate 15-lipoxygenase (ALOX15) (Gulliksson et al. 2007, Kuhn et al. 1993, Izumi et al. 1991) and arachidonate 15-lipoxygenase B (ALOX15B) (Tang et al. 2002, Wecksler et al. 2008) are lipid peroxidising enzymes mainly expressed in airway epithelial cells, eosinophils, reticulocytes and in macrophages. They insert molecular oxygen at C-6 from the omega-end of arachidonic acid with formation of the unstable intermediate 15S-hydroperoxyeicosatetraenoic acid (15S-HpETE) which can be further converted, enzymatically or non-enzymatically, to 15S-hydroxyeicosatetraenoic acid (15S-HETE). | |||
| REACT_150133 (Reactome) | Glutathione peroxidase 1 (GPX1) (Bryant et al. 1982, Sutherland et al. 2001), 2 (GPX2) (Chu et al. 1993), and 4 (Bryant et al. 1982, Sutherland et al. 2001) reduce 5-hydroperoxyeicosatetraenoic acid (5-HpETE) to 5-hydroxyeicosatetraenoic acid (5-HETE) in the presence of glutathione (GSH). This reaction is inferred from the event in rabbit involving the protein GPX1 (Chiba et al. 1999). | |||
| REACT_150141 (Reactome) | Analogous to prostaglandin E2 (PGE2), dehydration of the prostaglandin D2 (PGD2) prostane ring forms prostaglandin J2 (PGJ2) (Monneret et al. 2002). | |||
| REACT_150142 (Reactome) | The ring in prostaglandin I2 (PGI2) aka prostacyclin is highly labile and rapidly hydolyses to form the stable but biologically inactive 6-keto-prostaglandin F1alpha (6k-PGF1a) (Wada et al. 2004). PGI2 and 6k-PGF1a are often used interchangeably in the literature. | |||
| REACT_150143 (Reactome) | Current literature suggests that 5S-hydroxy-eicosatetraenoic acid (5S-HETE) itself does not appear to play a significant role in biological signalling. However, it can be further oxidised by a 5-hydroxy-eicosatetraenoic acid dehydrogenase (5-HEDH) to form the bioactive 5-oxo-eicosatetraenoic acid (5-oxoETE, also known as 5-KETE. While the gene has not yet been cloned, the biophysical properties of the human enzyme have been well characterised (Powell et al. 1992). | |||
| REACT_150156 (Reactome) | Arachidonate 5-lipoxygenase (ALOX5) (Ueda et al. 1987) converts 15S-hydroperoxy-eicosatetraenoic acid (15S-HpETE) into lipoxin A4 (LXA4) and B4 (LXB4) (Serhan et al. 1984A, Serhan et al. 1984B). One of the reaction intermediates of this process might be 5S,6S-epoxy-15S-hydroxy-7E,9E,11Z,13E-eicosatetraenoic acid (5,6-Ep-15S-HETE) (Puustinen et al. 1986). However, its generation from LTA4 is unclear but it can be hydrolysed to form the lipoxins. | |||
| REACT_150159 (Reactome) | Aspirin (acetylsalicylate) reacts spontaneously with one subunit of PTGS1 dimer to acetylate serine residue 516. The modified enzyme is no longer capable of catalyzing the conversion of arachidonic acid to PGH2. The identity of the acetylated residue is inferred from data for the humann PTGS2 enzyme (Lecomte et al. 1994) and the ovine PGHS1 enzyme (Loll et al. 1995). | |||
| REACT_150160 (Reactome) | Once omega-oxidation has occurred, 20-carboxy leukotriene B4 (20cooh-LTB4) can be further metabolized by beta-oxidation at its omega end into 18-carboxy-LTB4 (18cooh-LTB4) (Berry et al. 2003, Wheelan et al. 1999). The actual human enzyme or enzymes involved have yet to be identified. | |||
| REACT_150171 (Reactome) | Prostaglandin D2 (PGD2) is a structural isomer of prostaglandin E2 (PGE2). There is a 9-keto and 11-hydroxy group on PGE2 with these substituents reversed on PGD2. PGD2 is formed by two evolutionarily distinct, but functionally convergent, prostaglandin D synthases: lipocalin-type prostaglandin-D synthase aka Prostaglandin-H2 D-isomerase (PTDGS) and hematopoietic prostaglandin D synthase (HPGDS). One of the main differences between these two proteins is that HPGDS requires glutathione (GSH) for catalysis while PTDGS can function without this cofactor. Here, HPGDS with GSH promotes the isomerisation of prostaglandin H2 (PGH2) to prostaglandin D2 (PGD2) (Jowsey et al. 2001, Inoue et al. 2003). | |||
| REACT_150174 (Reactome) | Prostaglandin reductase 1 (PTGR1) aka LTB4DH is a 13-prostaglandin reductase which metabolises eicosanoids by catalysing NADH/NADPH-dependant double bond reduction in 15-keto-prostaglandin E2 (15k-PGE2) and F2alpha (15k-PGF2a) to produce 13,14-dihydro-15-keto-prostaglandin E2 (dhk-PGE2) and F2alpha (dhk-PGF2a) respectively (Yokomizo 1996). This has been inferred from the reaction event in mice involving prostaglandin reductase 2 (Ptgr2) (Chou et al. 2007). | |||
| REACT_150179 (Reactome) | Dehydration in the cyclopentane ring of prostaglandin E2 (PGE2) yields prostaglandin A2 (PGA2) followed by isomerization of the double bond to yield the unstable compound prostaglandin C2 (PGC2) (Straus & Glass, 2001). | |||
| REACT_150183 (Reactome) | Thromboxane A2 (TXA2) contains an unstable ether linkage that is rapidly hydrolysed under aqueous conditions to form the biologically inert thromboxane B2 (TXB2) (Wang et al. 2001, Hamberg et al. 1975), which is excreted. | |||
| REACT_150185 (Reactome) | Carbonyl reductase (CBR1) aka prostaglandin 9-keto reductase inactivates prostaglandin E2 (PGE2) by converting it to prostaglandin F2alpha (PGF2a) (Wermuth 1981, Miura et al. 2008). | |||
| REACT_150186 (Reactome) | 15-Hydroxyprostaglandin dehydrogenase (HPGD) oxidises prostaglandins D2 (PGD2), E2 (PGE2), and F2alpha (PGF2a) to 15-keto-prostaglandin D2 (15k-PGD2), E2 (15k-PGE2), and F2alpha (15k-PGF2a) respectively (Cho et al. 2006). This reaction is inferred from rabbits (Bergholte & Okita 1986). | |||
| REACT_150189 (Reactome) | Analogous to arachidonate 5-lipoxygenase (ALOX5) biosynthesis of leukotriene A4 (LTA4), arachidonate 15-lipoxygenase (ALOX15) can form an epoxide across C-14 and C-15 to form 14,15-LTA4 aka eoxin A4 (EXA4) (Feltenmark et al. 2008, Claesson et al. 2008). | |||
| REACT_150190 (Reactome) | Several cytochrome P450s (CYPs) convert arachidonic acid to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (8,9-, 11,12-, 14,15-EETs). The CYPs and their references are as follows: CYP1A1, CYP1A2, CYP1B1 (Choudhary et al. 2004); CYP2C8, CYP2C9 (Rifkind et al. 1995); CYP2C19 (Bylund et al. 1998, Rifkind et al. 1995); CYP2J2 (Wu et al. 1996). | |||
| REACT_150192 (Reactome) | In an analogous reaction to the formation of leukotriene D4 (LTD4), eoxin C4 (EXC4) is converted to eoxin D4 (EXD4) by a class of gamma-glutamyltransferase (GGT) (Feltenmark et al. 2008, Claesson et al. 2008) which has not yet been identified. | |||
| REACT_150194 (Reactome) | Prostamide/prostaglandin F synthase, FAM213B and thioredoxin (TXN) are the proteins involved in the reduction of prostaglandin H2 (PGH2) to prostaglandin F2alpha (PGF2a) (Moriuchi et al. 2008, Yoshikawa et al. 2011). This reaction has been inferred from an event in mice. An additional way of achieving this reaction involves the protein aldo-keto reductase family 1 member C3 (AKR1C3) aka PGFS. | |||
| REACT_150208 (Reactome) | Prostaglandin reductase 1 (PTGR1) aka LTB4DH, a 15-oxoprostaglandin 13-reductase (Yokomizo et al. 1996), metabolises 15-oxo lipoxin A4 aka 15-keto-LXA4 (15k-LXA4) to produce 13,14-dihydro-15-keto-Lipoxin A4 (dhk-LXA4). This reaction has been inferred from a reaction in pig (Clish et al. 2000). | |||
| REACT_150225 (Reactome) | Arachidonate released by phospholipases diffuses within the membrane and out of the membrane into the ER lumen and cytosol. The relatively low level of arachidonate in the cytoplasm is probably due to reesterification into complex lipids by acyl transferases. | |||
| REACT_150226 (Reactome) | The arachidonate 12-lipoxygenase, 12R-type (ALOX12B) oxidises arachidonic acid to 12R-hydroperoxy-eicosatetraenoic acid (12R-HpETE) (Boeglin et al. 1998). | |||
| REACT_150230 (Reactome) | Glutathione peroxidases (GPXs) in human platelets (either GPX1, GPX2, or GPX4 are present in the cytosol) are involved in reducing 15S-hydroperoxyeicosatetraenoic acid (15S-HpETE) to 15S-hydroxyeicosatetraenoic acid (15S-HETE) (Hill et al. 1989). | |||
| REACT_150241 (Reactome) | Aldo-keto reductase family 1 member C3 (AKR1C3) aka PGFS is responsible for the reduction of prostaglandin H2 (PGH2) to prostaglandin F2alpha (PGF2a) (Suzuki-Yamamoto et al. 1999, Komoto et al. 2004, Komoto et al. 2006). There is an additional way of achieving this reaction involving the prostamide/prostaglandin F synthase, FAM213B and thioredoxin (TRX). | |||
| REACT_150245 (Reactome) | A 15-hydroxy-eicosatetraenoic acid dehydrogenase (15-HEDH) oxidises 15S-hydroxyeicosatetraenoic acid (15S-HETE) to 15-oxo-eicosatetraenoic acid (15-oxoETE) (Gulliksson et al. 2007). The actual human 15-HEDH has yet to be cloned. | |||
| REACT_150255 (Reactome) | While closely similar, PTGS1 and 2 differ sufficiently in the structures of their active sites so that the latter enzyme selectively binds and is inhibited by celecoxib (Luong et al. 1996; Smith et al. 2000; Dong et al. 2011). | |||
| REACT_150262 (Reactome) | 15-Deoxy-delta(12,14)-PDJ2 (15d-PGJ2) is a dehydration product of delta-12-prostaglandin J2 (delta12-PGJ2) (Monneret et al. 2002). | |||
| REACT_150271 (Reactome) | Isomerization of the double bond in prostaglandin A2 (PGA2) forms prostaglandin C2 (PGC2). This is an unstable compound which undergoes a second isomerization to yield prostaglandin B2 (PGB2) (Straus & Glass, 2001). | |||
| REACT_150272 (Reactome) | Arachidonate 5-lipoxygenase (ALOX5) converts 15R-hydro-eicosatetraenoic acid (15R-HETE) to the epi-lipoxins, 15epi-lipoxin A4 (15epi-LXA4) and 15epi-lipoxin B4 (15epi-LXB4) (Claria & Serhan 1995). These epi-lipoxins have altered stereochemistry at the C-15 hydroxyl but similar biological potency. | |||
| REACT_150273 (Reactome) | In addition to its role converting leukotriene A4 (LTA4) into leukotriene C4 (LTC4), the enzyme leukotriene C4 synthase (LTC4S) analogously converts eoxin A4 (EXA4), with reduced glutathione (GSH), to eoxin C4 (EXC4) (Feltenmark et al. 2008, Claesson et al. 2008). | |||
| REACT_150274 (Reactome) | Epoxide hydrolase 2 (EPHX2) hydrolyses 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids ("EET(1)") to their corresponding dihydroxyeicosatrienoic acids ("DHET(1)") (Werner et al. 2002; Gomez et al. 2004). The majority of the EET biological activities are diminished by this hydrolysis. | |||
| REACT_150283 (Reactome) | An aldehyde dehydrogenase (ALDH) yet to be cloned in humans has been observed to oxidise 20-aldehyde leukotriene B4 (20cho-LTB4) to form 20-carboxy leukotriene B4 (20cooh-LTB4) (Sutyak et al. 1989). | |||
| REACT_150285 (Reactome) | 15-hydroxyprostaglandin dehydrogenase (HPGD) converted lipoxin A4 (LXA4) to 15-oxo lipoxin A4 aka 15-keto-LXA4 (15k-LXA4) (Clish et al. 2000). | |||
| REACT_150287 (Reactome) | Cytochrome P450s 1A1 (CYP1A1), 1A2 (CYP1A2), and 1B1 (CYP1B1) convert arachidonic acid to 16-, 17-, and 18-hydroxyeicosatetraenoic acids (16-, 17-, and 18-HETEs) (Choudhary et al. 2004). | |||
| REACT_150290 (Reactome) | The non-enzymatic dehydration of prostaglandin A2 (PGA2) into 15-deoxy prostaglandin A2 (15d-PGA2) which occurs in mice (Petrova et al. 1999) is inferred in humans. | |||
| REACT_150303 (Reactome) | Arachidonate 12-lipoxygenase, 12S-type (ALOX12) catalyses the conversion of leukotriene A4 (LTA4) into the lipoxins LXA4, which has its third hydroxyl positioned at C-6 and LXB4, which has it positioned at C-14 (Romano et al. 1993, Serhan & Sheppard 1990). One of the reaction intermediates of this process might be 5S,6S-epoxy-15S-hydroxy-7E,9E,11Z,13E-eicosatetraenoic acid (5,6-Ep-15S-HETE) (Puustinen et al. 1986). However, its generation from LTA4 is unclear but it can be hydrolysed to form the lipoxins. | |||
| REACT_150304 (Reactome) | The cytochrome P450s 4F2 (CYP4F2) and F3 (CYP4F3) oxidise the omega hydroxylated metabolite, 20-hydroxyleukotriene B4 (20oh-LTB4) to form 20-aldehyde leukotriene B4 (20cho-LTB4) (Soberman et al. 1988). | |||
| REACT_150327 (Reactome) | Arachidonate 12-lipoxygenase, 12S-type (ALOX12) catalyses the formation of 12-oxo-eicosatetraenoic acid (12-oxoETE) from arachidonic acid. This conversion has been observed when normal human epidermis is exposed to arachidonic acid and with the purified recombinant enzyme in vitro (Anton & Vila 2000). | |||
| REACT_150333 (Reactome) | Cyclopentenone prostaglandins comprise a family of molecules that are formed by dehydration of hydroxyl moieties in prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2). Dehydration of PGE2 leads to prostaglandin A2 (PGA2) (Hamberg & Samuelsson B 1966, Amin 1989). | |||
| REACT_150334 (Reactome) | Glutathione peroxidase 1 (GPX1) (Bryant et al. 1982, Sutherland et al. 2001), 2 (GPX2) (Chu et al. 1993), and 4 (Bryant et al. 1982, Sutherland et al. 2001) are involved in converting 12R-hydroperoxy-eicosatetraenoic acid (12R-HpETE) to 12R-hydro-eicosatetraenoic acid (12R-HETE). | |||
| REACT_150343 (Reactome) | Thromboxane synthase (TBXAS1) aka CYP5A1 facilitates rearrangement of the PGH2 endoperoxide bridge by a complementary mechanism to prostacyclin synthase, interacting with the C-9 oxygen to promote endoperoxide bond cleavage. The C-11 oxygen radical initiates intramolecular rearrangement, resulting in either the formation of thromboxane A2 (TXA2) or 12-hydroxyheptadecatrienoic acid (12S-HHT) and malonaldehyde (MDA) (Wang et al. 2001). | |||
| REACT_150346 (Reactome) | Thromboxane B2 (TXB2) undergoes dehydrogenation at C-11 to form 11-dehydro-thromboxane B2 (11dh-TXB2). The enzyme responsible for catalysis has been termed 11-dehydroxythromboxane B2 dehydrogenase (TXDH) (Kumlin & Granström 1986, Catella et al. 1986, Westlund et al. 1994). The human TXDH isoform has not been cloned but 11dh-TXB2 has been detected in various experiments. | |||
| REACT_150372 (Reactome) | Aspirin acetylates the cyclooxygenase, prostaglandin G/H synthase 2 (PTGS2) aka COX2. The acetylated PTGS2 triggers the formation of 15R-hydroxyeicosatetraenoic acid (15R-HETE) from arachidonic acid (Claria & Serhan 1995). | |||
| REACT_150378 (Reactome) | Prostaglandin D2 (PGD2) is a structural isomer of prostaglandin E2 (PGE2). There is a 9-keto and 11-hydroxy group on PGE2 with these substituents reversed on PGD2. PGD2 is formed by two evolutionarily distinct, but functionally convergent, prostaglandin D synthases: lipocalin-type prostaglandin-D synthase aka Prostaglandin-H2 D-isomerase (PTDGS) and hematopoietic prostaglandin D synthase (HPGDS). One of the main differences between these two proteins is that HPGDS requires glutathione (GSH) for catalysis while PTDGS can function without this cofactor. Here, PTDGS promotes the isomerisation of prostaglandin H2 (PGH2) to prostaglandin D2 (PGD2) (Zhou et al. 2010). | |||
| REACT_150384 (Reactome) | Delta-12-prostaglandin J2 (delta12-PGJ2) is an isomerisation product of prostaglandin J2 (PGJ2) (Monneret et al. 2002). | |||
| REACT_150391 (Reactome) | Glutathione peroxidase 1 (GPX1) (Bryant et al. 1982, Sutherland et al. 2001), 2 (GPX2) (Chu et al. 1993), and 4 (Bryant et al. 1982, Sutherland et al. 2001) are involved in converting 12S-hydroperoxy-eicosatetraenoic acid (12S-HpETE) to 12S-hydro-eicosatetraenoic acid (12S-HETE). GPXs are selenoenzymes that are responsible for reducing the cellular peroxide. Cellular GPXs compete with hepoxilins A3 (HXA3) synthase for 12S-HpETE as substrate either to produce 12S-HETE or to convert to HXA3, respectively. | |||
| REACT_150394 (Reactome) | The cytochrome P450s 4F2 (CYP4F2) and F3 (CYP4F3) oxidise 20-aldehyde leukotriene B4 (20cho-LTB4) to form 20-carboxy leukotriene B4 (20cooh-LTB4) (Soberman et al. 1988). | |||
| REACT_150400 (Reactome) | 15-Deoxy-delta 12,14-prostaglandins D2 (15d-PGD2) is a dehydrated form of prostaglandin D2 (PGD2) (Monneret et al. 2002). | |||
| REACT_150406 (Reactome) | Several cytochrome P450s (CYPs) convert arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE). The CYPs and their references are as follows: CYP4A11 (Gainer et al. 2005, Powell 1998); CYP4F2 (Powell et al. 1998, Kikuta et al. 2002); CYP2U1 (Chuang et al. 2004); CYP1A1, CYP1A2, CYP1B1 (Choudhary et al. 2004). | |||
| REACT_150407 (Reactome) | Prostaglandin E synthase (PTGES) requires glutathione (GSH) as an essential cofactor for its enzymatic activity, and together they isomerise prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2) (Jegerschold et al. 2008). After PGH2 has been produced by the prostaglandin G/H synthases (PTGS1 and 2) on the lumenal side of the endoplasmic reticulum, it diffuses through the membrane to the active site of PTGES located on the cytoplasmic side. | |||
| REACT_150408 (Reactome) | PGH2 moves from the endoplasmic reticulum to the cytosol. The mechanism of this movement has not been determined and could could simply be diffusion through the ER membrane. | |||
| REACT_150426 (Reactome) | The epoxy moiety of hepoxilin A3 (HXA3) and B3 (HXB3) is labile and can be hydrolysed either by a hepoxilin specific epoxide hydrolase (HXEH) or in acidic aqueous solution to form the corresponding diol metabolites trioxilin A3 (TrXA3) and B3 (TrXB3) (Anton et al. 1995, Anton et al. 1998, Pace-Asciak et al. 1983, Pace-Asciak & Lee 1989). | |||
| REACT_150428 (Reactome) | In an analogous reaction to the formation of leukotriene E4 (LTE4), eoxin D4 (EXD4) is converted to eoxin E4 (EXE4) by a dipeptidase (DPEP) (Feltenmark et al. 2008, Claesson et al. 2008) which has not yet been identified. | |||
| REACT_150433 (Reactome) | Arachidonate 12-lipoxygenase, 12S-type (ALOX12) (Funk et al. 1990, Izumi et al. 1990) and arachidonate 15-lipoxygenase (ALOX15) (Kuhn et al. 1993, Sigal et al. 1990) convert arachidonic acid into 12S-hydroperoxy-eicosatetraenoic acid (12S-HpETE). | |||
| REACT_150441 (Reactome) | Several cytochrome P450s (CYPs) convert arachidonic acid to 19-hydroxyeicosatetraenoic acid (19-HETE). The CYPs and their references are as follows: CYP2C8 (Bylund et al. 1998); CYP2C9 (Bylund et al. 1998); CYP2C19 (Bylund et al. 1998); CYP4A11 (Gainer et al. 2005); CYP2U1 (Chuang et al. 2004); CYP1A1, CYP1A2, CYP1B1 (Choudhary et al. 2004). | |||
| REACT_150442 (Reactome) | Several cytochrome P450s (CYPs) convert arachidonic acid to 5,6-epoxyeicosatrienoic acid (5,6-EET). The CYPs and their references are as follows: CYP1A1, CYP1A2, CYP1B1 (Choudhary et al. 2004); CYP2J2 (Wu et al. 1996). | |||
| REACT_150443 (Reactome) | Aldo-keto reductase family 1 member C3 (AKR1C3) aka PGFS is the enzyme involved in NADPH-dependent prostaglandin D2 11-keto reductase activity of reducing prostaglandin D2 (PGD2) to 11-epi-Prostaglandin F2alpha (11-epi-PGF2a) (Liston & Roberts 1985, Koda et al. 2004). | |||
| REACT_150446 (Reactome) | Aspirin (acetylsalicylate) reacts spontaneously with one subunit of PTGS2 dimer (Dong et al. 2011) to acetylate serine residue 516 (Lecomte et al. 1994). The modified enzyme is no longer capable of catalyzing the conversion of arachidonic acid to PGH2, but acquires the ability to convert it to 15R-HETE. | |||
| REACT_150449 (Reactome) | Prostaglandin reductase 1 (PTGR1) aka LTB4DH metabolizes eicosanoids by catalysing the oxidation of leukotriene B4 (LTB4) to form 12-oxo-Leukotriene B4 (12-oxoLTB4) aka 12-Keto-LTB4. The gene was originally cloned as leukotriene B4 12-hydroxydehydrogenase (LTB4DH) but was later discovered to have dual functionality as a prostaglandin reductase (Yokomizo et al. 1996). This reaction has been inferred from a reaction in pigs (Yokomizo et al. 1993, Ensor et al. 1998). | |||
| REACT_150455 (Reactome) | Non-enzymatic hydrolysis of the leukotriene A4 (LTA4) epoxide bond creates 6-trans leukotriene B4 (6t-LTB4) and 6-trans,12-epi leukotriene B4 (6t,12epi-LTB4) stereoisomers (Mansour & Agha 1999, Sirois et al. 1985). | |||
| REACT_15331 (Reactome) | Once bound to the membrane, cPLA2 hydrolyzes phosphatidylcholine to produce arachidonic acid (AA), a precursor to inflammatory mediators. While several phospholipases can catalyze this reaction in cells overexpressing the enzymes, PLA2G4A is the major enzyme that catalyzes this reaction in vivo (Reed et al. 2011). At the same time, possible physiological roles have been described for soluble phospholipases (sPLA) in the mobilization of arachidonic acid in some cell types or under some physiological conditions (Murakami et al. 2011). Here, the major role of PLA2G4A has been annotated. | |||
| REACT_15337 (Reactome) | Arachidonate 5-lipoxygenase (ALOX5) catalyzes the formation of leukotriene A4 (LTA4) from arachidonic acid in a two-step process. First, arachidonic acid AA is oxidized to form 5S-hydroperoxyeicosatetranoic acid (5S-HpETE) (Rouzer et al. 1988, Rouzer & Samuelsson 1987, Rouzer et al. 1986). | |||
| REACT_15356 (Reactome) | The reversible conversion of leukotriene C4 (LTC4) to leukotriene D4 (LTD4) is catalysed by gamma-glutamyl transferases 1 (GGT1) and 5 (GGT5). GGTs are present on the outer surface of plasma membranes and are a heterodimer of a heavy and a light chain. Its action involves the cleavage of the gamma-glutamyl peptide bond of glutathione conjugates, releasing glutamate (Anderson et al. 1982, Wickham et al. 2011). | |||
| REACT_15395 (Reactome) | Another outer surface membrane-bound, homodimeric enzyme, dipeptidase, existing in two forms DPEP1 (Adachi et al. 1989) and DPEP2 (Lee et al. 1983, Raulf et al. 1987), further hydrolyses leukotriene D4 (LTD4) to leukotriene E4 (LTE4), cleaving a glycine residue in the process. | |||
| REACT_15413 (Reactome) | Leukotriene A4 conjugates with reduced glutathione (GSH) to produce leukotriene C4 (LTC4). This conjugation is mediated by the homodimeric, perinuclear membrane-bound enzyme leukotriene C4 synthase (LTC4S) (Lam et al. 1994, Welsch et al. 1994). LTC4S differs from cytosolic and microsomal GSH-S-transferases by having a very narrow substrate specificity and the inability to conjugate xenobiotics. | |||
| REACT_15453 (Reactome) | In the second step of the formation of leukotriene A4 (LTA4) from arachidonic acid, arachidonate 5-lipoxygenase (ALOX5) converts 5S-hydroperoxyeicosatetranoic acid (5S-HpETE) to an allylic epoxide, leukotriene A4 (LTA4) (Rouzer et al. 1988, Rouzer & Samuelsson 1987, Rouzer et al. 1986). | |||
| REACT_15459 (Reactome) | Prostaglandin E2 (PGE2) is the most abundant prostanoid in the body and is a major mediator of inflammation in diseases such as osteoarthritis and rheumatoid arthritis. The product of arachidonic acid, prostaglandin H2 (PGH2) serves as the substrate for the isomerization to PGE2. The conversion is carried out by prostaglandin E synthase (PGES), of which there are three forms. Two are membrane-bound enzymes and are designated as mPGES-1 (functionally linked with COX-2) and mPGES-2 (golgi membrane-associated, functionally coupled with both COX-1 and COX-2). The other is cytosolic (cPGES, PTGES3) and functionally linked to COX-1 to produce PGE2 immediately. In this reaction, cPGES is used for conversion of PGH2 to PGE2. | |||
| REACT_15474 (Reactome) | On formation, leukotriene C4 (LTC4) is exported to the extracellular region by the ABCC1 transporter (Sjolinder et al. 1999, Lam et al. 1989) and processed further by cleavage reactions. | |||
| REACT_15478 (Reactome) | Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that catalyzes the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) to the dihydroxy acid leukotriene B4 (LTB4) (Radmark et al. 1984, McGee & Fitzpatrick 1985). | |||
| REACT_1841 (Reactome) | Prostacyclin synthase (PTGIS) aka CYP8A1 mediates the isomerisation of prostaglandin H2 (PGH2) to prostaglandin I2 (PGI2) aka prostacyclin (Wada et al. 2004). This reaction is not coupled with any P450 reductase proteins nor consumes NADPH. | |||
| REACT_22105 (Reactome) | Arachidonate 5-lipoxygenase (ALOX5) catalyzes the first step in leukotriene biosynthesis and has a key role in inflammatory processes. ALOX5 is phosphorylated by MAPKAPK2; MAPKAPK2 is stimulated by arachidonic acid. | |||
| REACT_528 (Reactome) | Prostaglandin G/H synthase PTGS1 exhibits a dual catalytic activity, a cyclooxygenase and a peroxidase. The cyclooxygenase function catalyzes the initial conversion of arachidonic acid to an intermediate, prostaglandin G2 (PGG2) (Hamberg et al. 1974, Nugteren 1973). | |||
| REACT_810 (Reactome) | Prostaglandin G/H synthase 1 (PTGS1) exhibits a dual catalytic activity, a cyclooxygenase and a peroxidase. The peroxidase function converts prostaglandin G2 (PGG2) to prostaglandin H2 (PGH2) via a two-electron reduction (Hamberg et al. 1973, Hla & Neilson 1992, Swinney et al. 1997, Barnett et al. 1994). | |||
| TBXAS1 | REACT_1377 (Reactome) | |||
| TBXAS1 | REACT_150343 (Reactome) | |||
| TXA2 | REACT_150183 (Reactome) | |||
| TXB2 | REACT_150346 (Reactome) | |||
| TXDH | REACT_150346 (Reactome) | |||
| TXN-S2 | Arrow | REACT_150194 (Reactome) | ||
| TXN-S2H2 | REACT_150194 (Reactome) | |||
| acetylsalicylate | REACT_150159 (Reactome) | |||
| acetylsalicylate | REACT_150446 (Reactome) | |||
| celecoxib | REACT_150255 (Reactome) | |||
| dhk-LXA4 | Arrow | REACT_150208 (Reactome) | ||
| dhk-PGE2/F2a | Arrow | REACT_150174 (Reactome) | ||
| e- | REACT_147811 (Reactome) | |||
| e- | REACT_810 (Reactome) | |||
| p-T222,S272,T334-MAPKAPK2 | REACT_22105 (Reactome) | |||
| salicylate | Arrow | REACT_150159 (Reactome) | ||
| salicylate | Arrow | REACT_150446 (Reactome) |
