Fig. 5.1.

Metabolic fate of polyunsaturated fatty acids Free fatty acids are primarily metabolized through β-oxidation, Cyclooxygenase (COX), Lipoxygenase (LOX or LO), and CytochromeP450 (CYP450). A simplistic overview of the biological action of the resulting metabolites is shown in parenthesis.

COX 1 and COX 2 metabolize PUFA to PGH2 which is the precursor to other inflammatory prostanoids and thromboxanes that regulate the immune system (PGD₂), increase pain and inflammation (PGE₂) and control platelet aggregation (PHI₂ and TXA₂). [108]

5-LO metabolizes PUFA to 5-HpETE or 15-LO to 15-HpETE, both are precursors to inflammatory leukotrienes and cytotoxic leukotoxins. These metabolites are important in exacerbating asthma by acting as powerful bronchoconstrictors, and they can also sustain inflammatory reactions through chemotaxis of inflammatory mediators. LO metabolism of omega-3 fatty acids result in pro-resolving lipid mediators called Resolvins, Protectins and Maresins. [139]

CYP450 metabolizes PUFA to anti-i nflammatory epoxy fatty acids (EpFAs), n-terminal hydroxylated n-HETE, ω−1 oxidation, or allylic hydroxylations. 20-HETE regulates blood pressure by acting as a potent vasoconstrictor in kidneys and preventing sodium reabsorption in nephrons [140, 141]. The biological significance of mid-chain hydoxylations is less understood; however, biological significance has been observed with 12-HETE in corneal inflammation and neovascularization [142, 143]. Formation of EpFA, particularly if induced, is primarily accomplished by CYP2C and CYP2J subfamily; however, other CYP enzymes can generate EETs [144]. The EpFA act as homeostatic regulators to other metabolites in this pathway by stabilizing mitochondria, reducing ROS, decreasing ER-stress [20] and inflammation [15], regulating the vascular endothelium [88] and increasing bronchodilation [145]