Arachidonate metabolism in blood cells and the vessel wall.

Abstract

Arachidonic acid (AA) is metabolized by the cyclo-oxygenase and the lipoxygenase pathways to give a number of products, some of which have potent and sometimes opposing biological activities. Different cell types produce different metabolites, so that the chief AA metabolite produced by the platelet is the pro-aggregatory thromboxane A2 (TXA2), whereas that produced by the vascular endothelium is the anti-aggregatory prostacyclin. White blood cells, on the other hand, are the chief source of the leukotrienes, which are implicated in the inflammatory process. Generation of these products may be modified in certain pathological conditions, such as atherosclerosis and diabetes, where prostacyclin synthesis is reduced and TXA2 synthesis increased, resulting in a pro-thrombotic state. Synthesis of AA metabolites may be inhibited, either totally or selectively, using drugs which inhibit different enzymes in the metabolic pathway. These drugs may be beneficial in the treatment of thrombotic disorders and inflammation. AA metabolism may also be modified by dietary substitution with eicosapentaenoic acid, a fatty acid present in fish oils.