Eicosanoid Signaling


Pathway Description

There are four types of eicosanoids: prostaglandins, lipoxins, leukotrienes and thromboxanes. Arachidonic acid (AA), the precursor for most eicosanoids, is produced by hydrolysis of membrane phospholipids by phospholipaseA2 (PLA2). AA is then converted to eicosanoids by one of two types of enzymes: 1) Prostaglandin endoperoxide synthases (PTGS), commonly referred to as cyclooxygenases (COX-1 and COX-2), catalyze the key step in the synthesis of biologically active prostaglandins, the conversion of arachidonic acid (AA) into prostaglandin H2 (PGH2). PGH2 serves as the precursor for thromboxanes, prostaglandins and prostacyclins.2) The lipoxygenases include ALOX5, ALOX12 and ALOX15. ALOX5 catalyzes the key step in the conversion of AA to leukotriene A4, B4 and C4. ALOX15 in concert with ALOX5 is involved in the formation of lipoxins A4 and B4.ALOX12 synthesizes 12(S)-HETE[12(S)-hydroxyeicosatetraenoic acid].

Eicosanoid receptors belong to the family of G-protein coupled receptors. Some of these receptors include BLT-1,-2 and CYSLTR1 and CYSLTR2 for leukotrienes, PTGERs for Prostaglandin E2, PTGFR for prostaglandin F2, PTGDR for prostaglandin D2 and TBXA2R for thromboxane A2. Eicosanoids transduce signals via their membrane receptors and mediate complex biological processes like inflammation, vascular permeability, allergic reactions, induction of labor and carcinogenesis.