Cyclooxygenase-mediated prostaglandin E2 biosynthetic pathway (PGE2 pathway)

The cyclooxygenase-mediated prostaglandin E2 (PGE2) biosynthetic pathway is a multi-step enzymatic process that generates PGE2, a key lipid mediator of inflammation, pain, and fever [1.4.1, 1.4.3]. The pathway begins with the liberation of arachidonic acid from cell membrane phospholipids by phospholipase A2 (PLA2), which is then converted into the unstable intermediate prostaglandin H2 (PGH2) by the cyclooxygenase enzymes COX-1 and COX-2 [1.1.5, 1.2.3]. PGH2 is subsequently transformed into PGE2 by specific prostaglandin E synthases, primarily the inducible microsomal prostaglandin E synthase-1 (mPGES-1) [1.4.1]. PGE2 signals through four G protein-coupled receptors (EP1-EP4), influencing diverse physiological processes such as gastric mucosal protection, renal function, and immune regulation [1.2.1, 1.2.3]. Dysregulation of this pathway, particularly the overexpression of COX-2 and mPGES-1, is strongly linked to chronic inflammatory conditions and the progression of various cancers, where PGE2 promotes tumor cell survival, angiogenesis, and immunosuppression [1.2.1, 1.3.1]. While nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors are widely used to target this pathway, they are associated with significant gastrointestinal and cardiovascular safety concerns [1.5.1, 1.5.2]. Current research is focused on developing more selective inhibitors, such as mPGES-1 inhibitors and EP receptor antagonists, to achieve therapeutic benefits with reduced side effects [1.4.1, 1.5.1].

Other names

PGE2 biosynthetic pathwayCOX-PGE2 pathwayArachidonic acid-PGE2 pathwayProstaglandin E2 synthesis pathway

Inhibition of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes; inhibition of microsomal prostaglandin E synthase-1 (mPGES-1); antagonism of prostaglandin E receptors (EP1, EP2, EP3, and EP4).