Arachidonic Acid and Eicosanoids
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Introduction
Eicosanoids are a family of compounds including prostaglandins (PG), thromboxanes (TX), and leukotrienes (LT) that are produced by many cell types, including macrophages, monocytes, neutrophils, and mast cells.
Eicosanoids originate from arachidonic acid - a polyunsaturated fatty acid with 20 carbons derived from linoleic acid. Arachadonic acid is released from membrane-bound phospholipids by phospholipase A2.
PGH2 is the result of oxidative cyclization of free arachadonic acid by prostaglandin endoperoxide synthase and its cyclooxygenase (COX) subunit.
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Prostaglandins
Prostaglandins are derived from arachidonic acid, which originates from membrane phospholipids (linoleic acid), by the action of phospholipase A2. Metabolism to prostaglandins and leukotrienes is catalyzed by the cyclooxygenase (COX) pathway and 5-lipoxygenase (LOX) pathway, respectively.
...prostaglandin G2 by the cycloxygenase pathway.
- Monocytes and macrophages produce large amounts of PGE2 and PGF2
- Neutrohils produce large amounts of PGE2
- Mast cells produce large amounts of PGD2
Function
- increased vascular permeability
- increased vascular dilation
- neutrophil chemotaxis
- increased natriuresis by acting on the kidney collecting duct
In the stomach, prostaglandins are thought to be involved in production of gastric mucus, secretion of HCO3, mucosal blood flow, and epithelial proliferation.
Prostacyclin
Prostacyclin (PGI2) is a potent vasodilator, inhibitor of platelet aggregation, and potentiator of other permeability-increasing factors. It thusly plays an important antithrombotic effect, counteracting hemostasis and thrombus formation.
Endothelium lacks thromboxane synthetase but possesses prostacyclin synthetase.
A thromboxane-prostacyclin imbalance has been implicated as an early event in thrombus formation.
Throboxane A2
Synthesized and released by platelets during hemostasis, throboxane A2 (TxA2) is a potent vasoconstrictor and mediator of platelet aggregation. The clinical use of aspirin is largely due to irreversible acetylation of cyclooxygenase and inhibition of TxA2 formation.
- vasoconstrictor
- platelet agregator
Leukotrienes
down into leukotriene A4 by the lipoxygenase pathway.
- induce smooth muscle contraction
- neutrophil chemotaxis
arachidonic acid, produced from membrane phospholipids (linoleic acid), is broken
Resources and References
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