Biosynthesis of E-series 18(R)-resolvins

Eicosapentaenoic acid (EPA), a major ω-3 polyunsaturated fatty acid (PUFA) found in fish oil is the source of E-series resolvins, one of the specialized proresolving mediators (SPMs) that show potent anti-inflammatory and pro-resolving actions. The initial transformation of EPA can be mediated by either cytochrome P450s or aspirin-acetylated cyclooxygenase-2, resulting in 18(R)- and 18(S)-stereospecific E-resolvins. Combinations of oxidation, reduction and hydrolysis reactions determine the type of E-resolvin formed (RvE1, RvE2 or RvE3). Aspirin acetylation of cyclooxygenase isoforms results in changed activities. Acetylation of cyclooxygenase-1 results in its inhibition and thereby halting production of inflammatory mediators. However, acetylation of cyclooxygenase-2 transforms its enzyme activity from a cyclooxygenase to a lipoxygenase, thereby blocking prostaglandin biosynthesis and, additionally, initiating the production of SPMs. The biosynthesis of 18(R) E-resolvins is described here.

Summary from Reactome (R-HSA-9023661), read 2026-09-23.