Fig.2.

Long chain polyunsaturated fatty (LCPUFA) signaling and metabolism: LCPUFAs, namely omega-6 and omega-3, must be derived from the diet to elicit intracellular signaling cascades through G-protein coupled receptors (GPCRs) or be incorporated into the cellular membrane for future use. Shorter omega-6 or -3 LCPUFAs like linoleic or α-linoleic acid, respectively, can be further metabolized by the same enzymes to yield the longer LCPUFAs arachidonic acid (AA) or eicosapentaenoic acid (EPA). Newly formed AA and EPA can then be incorporated into the phospholipid membrane for future use. Upon an external stimulus like a cytokine or growth factor, AA and EPA can be liberated from the membrane by phospholipase A₂ (PLA₂) and metabolized into bioactive compounds by the rate limiting enzymes cyclooxygenase (COX), lipoxygenase (LOX), or cytochrome P450 (CYP). These bioactive compounds can then activate extracellular GPCRs in an autocrine or paracrine fashion to elicit downstream signaling cascades.