Figure 2.
A schematic representation of the arachidonic acid metabolism pathway. After its liberation by phospholipases, ((i.e., phospholipase A2 (PLA2) or phospholipase C (PLC)), the free arachidonic acid may undergo enzymatic metabolism by the lipoxygenases which produce HPETEs and leukotrienes, and the cyclooxygenases (COX-1, COX-2) which generate prostaglandins and thromboxanes. The specific repertoire of the arachidonic acid metabolites produced may vary according to the expression profile of these enzymes in different cell types. In platelets, for example, arachidonic acid is metabolized by COX-1 into the prostaglandin endoperoxides, PGG2 and PGH2. Next, thromboxane synthetase further metabolizes PGH2 into TXA2, which is a potent activator of platelet aggregation, with a half-life of 20-30 seconds. Thromboxane A2 is then hydrolyzed to the inactive form TXB2 (not shown). On the other hand, if PGH2 is metabolized by prostacyclin synthetase, then PGI2 would be produced (e.g., in endothelial cells). Furthermore, if PGH2 is acted upon by PGD or PGE isomerase, then PGD2, and PGE2 are produced, respectively (e.g., in renal cells). Finally, if the PG reductase metabolizes PGH2, then PGF2α is produced (e.g., pulmonary vessels). Thus, the biological functions of arachidonic acid are exerted indirectly after its metabolism into prostaglandin and thromboxane metabolites.