Figure 1.

Cyclooxygenase and 5-lipoxygenase pathways with special reference to aspirin exacerbated respiratory disease. Simplified pictogram of biosynthetic pathways of prostaglandin (PG) E₂ and cysteinyl leukotrienes (CysLTs). Arachidonic acid (AA) is metabolized by the cyclooxygenase (COX) or 5-lipoxygenase (5-LO) pathways. COX enzymes generate PGH₂ which through PGE₂ synthase is converted into PGE₂. PGE₂ couples to four subtypes of G-protein-coupled membrane receptors denominated E-prostanoid (EP) receptors. The activation of EP2 and EP4 receptors generates cyclic adenosine monophosphate (cAMP). This mediator negatively regulates the 5-LO pathway by activating protein kinase A (PKA). AA is also metabolized by the 5-LO pathway to generate leukotriene (LT) A₄. LTA₄ is subsequently metabolized by LTC₄ synthase, which conjugates reduced glutathione into LTC₄. LTC₄ is metabolized into LTD₄, which is then metabolized into LTE₄. LTC₄, LTD₄ and LTE₄ are designated as CysLTs. CysLTs bind to CysLT₁, CysLT₂ and GPR17 receptors. In aspirin exacerbated respiratory disease (AERD) the inhibition of COX pathway accounts for a reduced production of cAMP since the production of PGE₂ is diminished. This is a simplified pictogram where some pathways and compounds generated are not mentioned.