Figure 1.
Arachidonic acid metabolism. Cell damage and phospholipase activation release arachidonic acid with subsequent oxidation to a variety of eicosanoids. Arachidonic acid is converted to highly labile prostanoids and leukotrienes by COXs and lipoxygenases, respectively, producing reactive oxygen free radicals in the process. Alternatively, arachidonic acid can be monooxygenated by cytochrome P450 epoxygenases, producing highly labile epoxide regioisomers (5,6-; 8,9-; 11,12-; or 14,15-EET)(Chacos et al., 1982; Oliw et al., 1982). Allylic oxidation is also catalyzed to form HETEs (5-, 8-, 9-, 11-, 12-, 15-, 19-, or 20-HETE)(Capdevila et al., 1982; Oliw et al., 1982). Certain HETEs (e.g., 5-, or 12-HETE) can also be formed via lipoxygenase action from hydroperoxyeicosatetraenoic acid (HPETE) precursors. EETs are metabolized by epoxide hydrolase to the corresponding dihydroxyeicosatrienoic acids (DHETs)(Chacos et al., 1983; Oliw et al., 1982; Yu et al., 2000b; Zeldin et al., 1995). Interestingly, EETs and HETEs are often incorporated in membrane phospholipid, enabling phospholipase-mediated release of these activities (Brezinski and Serhan, 1990; Capdevila et al., 1987; Karara et al., 1991).