Convergent Oxygenation of Arachidonic Acid by 5-Lipoxygenase and Cyclooxygenase-2

5-Lipoxygenase and cyclooxygenase-2 (COX-2) initiate the biosynthesis of distinct families of mediators from arachidonic acid (leukotrienes and prostaglandins, respectively) and are each the target of anti-inflammatory medications. Here we show that the product of 5-lipoxygenase, 5S-hydroxyeicosatetraenoic acid, is selectively and efficiently triply oxygenated by COX-2, implicating a cross-pathway interaction. The product is a unique diendoperoxide, potentially representing the parent compound of a novel group of lipid mediators.