Lipid Mediators Are Critical in Resolving Inflammation: A Review of the Emerging Roles of Eicosanoids in Diabetes Mellitus

Figure 1

Eicosanoid synthesis pathways. After cell stimulation, arachidonic acid (AA) can be metabolized by three enzymes: cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP 450). COX catalyzes AA in (prostaglandin) PGG₂ and PGH₂, and these are converted into PGD₂, PGE₂, PGF_2α, PG₁₂, , and . The LOX pathway catalyzes AA into hydroxyeicosatetraenoic acids (HETEs) and diverse hydroperoxyeicosatetraenoic acids (HPETEs). This pathway involves four enzymes: 5-LOX, 8-LOX, 12-LOX, and 15-LOX. 5-LOX interacts with a 5-LOX-activating protein (FLAP), enhancing the interaction of 5-LOX to AA. LTA₄ hydrolases convert LTA₄ into LTB₄, and LTC₄ synthase can convert LTA₄ to LTC₄, whereupon it is then metabolized to LTD₄ and LTE₄. 5-LOX synthetizes LXA₄ and LXB₄ using 15-HETE. The pathway of CYP-450 leads to the conversion of HETEs, including 16-, 17-, 18-, 19-, and 20-HETE and epoxyeicosatrienoic acids (EETs): 5,6-, 8,9-, 11,12-, and 14,15-EET.