Microsomal Prostaglandin E₂ Synthase: A Safer Target than Cyclooxygenases?

Prostaglandin biosynthesis pathway. Phospholipase A₂ catalyzes the release of arachidonic acid (AA) from the membrane, and AA is converted into prostaglandin G₂ and H₂ by prostaglandin G/H synthase (PGHS)-1 or -2, which contain both cyclooxygenase activity and hydroperoxidase activity. COX-1 is constitutively expressed in many organs, whereas the expression of COX-2 is inducible. Prostaglandin H₂ is further metabolized by tissue specific isomerases and synthases [such as PGE synthases (e.g., microsomal PGE synthase-1) or PGI synthase] to generate diverse prostaglandins. Tx, thromboxane; PG, prostaglandin.