Eicosanoids synthetic pathway

Because steroids inhibit the release of arachidonic acid, their use shuts down the synthesis of most if not all eicosanoid molecules, hence their reputation as potent anti-inflammatory agents. Aspirin inactivates cyclooxygenase and prevents the conversion of arachidonic acid to PGG2, the precursor of prostaglandins and thromboxanes. Aspirin is not as effective an anti-inflammatory agent as the steroids because it shuts down only a portion of eicosanoid synthetic pathways. 

The synthesis of eicosanoids begins with arachidonic acid (C20 4 n-6 fatty acid) which is component part of cell membranes. The synthetic pathway is outlined in Figure 4.8. A key enzyme in this process is cyclo-oxygenase (COX) which occurs in two... 

Eicosanoids, also referred to as icosanoids, are so named because of the 20-carbon constituency that identifies this class of oxygenated lipid molecules. A primary synthetic pathway for these molecules involves the phospholipase-mediated cleavage of a membrane phospholipid to produce arachidonic acid [(all-Z)-ik osa-5,8,ll,14-tetraenoic acid]. From this biologically essential intermediate fatty acid, two major subclasses of eicosanoids can be produced 1) leukotrienes, via the action of lipooxygenases, and 2) prostanoids, via the action of cyclooxygenases (COX-1 and COX-2). Examples of chemical structures for a leukotriene (Fig. la) and three types of prostanoids (Fig. Ib-d) underscore their shared arachidonate origin. 

Precursor and product relationships of eicosanoids prostaglandins (PGs), prostacyclins (PGIs), thromboxanes (TXs), and leukotrienes (LTs). Arrows arising from each fatty acid indicate two different synthetic pathways one for prostanoids (PG, PGI, TX) and the other for leukotrienes. The numerical subscript of an eicosanoid indicates the total number of double bonds in the molecule and thus the series to which it belongs. The prostanoids contain two fewer double bonds than does the precursor fatty acid. 

---