Arachidonic acid (ARA) pathway.

<p>ARA is metabolized by three enzyme families, cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450), to produce numerous bioactive metabolites called oxylipins. Enzymes are shown in grey boxes. Oxylipin class and biological activity are outlined in black below the oxylipins they represent. The COX arm produces prostaglandins and thromboxanes that are pro-inflammatory, can cause pain, and can stimulate chemokine production. The LOX arm produces lipoxins, leukotrienes, and hydroxyeicosatetraenoic acids that are also pro-inflammatory and can stimulate chemokine production, with the exception of LXA₄ which is anti-inflammatory. The CYP450 arm produces epoxyeicosatrienoic acids that decrease inflammation and are cardioprotective; however, these oxylipins are quickly metabolized by soluble epoxide hydrolase (sEH) to produce epoxyeicosatrienoic acid diols that are pro-inflammatory as well as cardiotoxic. The CYP450 arm also produces 20-hydroxyeicosatetraenoic acid (20-HETE), which is pro-inflammatory and cardiotoxic. Only oxylipins from the ARA pathway that were quantified on our analytical platform are depicted, excluding THF diol which is produced from multiple epoxyeicosatrienoic acids.