Figure 2. Prostaglandin E₂ synthesis pathway.

The initial step of PGE₂ synthesis is the stimulus-induced liberation of AA from the membrane phospholipids by PLA₂ enzymes. AA is then sequentially metabolized into PGG₂ and then to PGH₂ by either COX-1 or COX-2. PGH₂ is an unstable intermediate prostanoid, which is rapidly converted into various prostanoids by specific terminal prostaglandin synthases, of which prostaglandin E synthases (mPGES-1, mPGES-2 and cPGES) generate PGE₂ from PGH₂. The other synthases include PGIS that forms PGI₂, PGDS for PGD₂, PGFS for PGF_2α and TXS for TXA₂. PGI₂ is non-enzymatically metabolized to the more stable 6-keto PGF_1α. PGE₂ mediates inflammation, stimulates cell growth and angiogenesis, and also inhibits apoptosis.

^†Upregulated in cancers.

AA: Arachidonic acid; PGDS: Prostaglandin D synthase; PGE₂: Prostaglandin E₂; PGFS: Prostaglandin F synthase; PGIS: Prostaglandin I synthase; PLA₂: Phospholipase A₂; TXA₂: Thromboxane A₂; TXS: Thromboxane synthase.