Synthesis of 20-Hydroxy Arachidonic Acid by the Human Neutrophil and Platelet Metabolism

Abstract

Arachidonic acid is oxidatively metabolized into numerous, structurally diverse molecules following cell activation. Considerable work has focused on two pathways of arachidonic acid metabolism, the cyclooxygenase pathway which leads to the formation of prostaglandins and thromboxanes (1) and the 5-lipoxygenase pathway which leads to the formation of leukotrienes (2). However, a third pathway exists for oxidative metabolism of arachidonic acid, that being the cytochrome P450 pathway which also leads to the formation of biologically active molecules (3). Much of our understanding of the formation of such eicosanoids has resulted from studies of arachidonic acid metabolism in purified cell populations. More recently, it has become clear that cells cooperate in the biochemical processing of chemically reactive intermediates synthesized from arachidonate by the cyclooxygenase and 5-lipoxygenase pathway in the ultimate formation of the biologically active compound. A particular example is the transcellular biosynthesis of LTC4 as a result of neutrophil-platelet interactions (4). There has been little evidence to suggest involvement of the cytochrome P450 pathway of arachidonic acid metabolism in such transcellular biosynthetic events.