Prostaglandin E2 biosynthesis pathway enzymes

The Prostaglandin E2 (PGE2) biosynthesis pathway enzymes are a group of catalytic proteins that orchestrate the production of PGE2, a key lipid mediator involved in inflammation, pain, and physiological homeostasis [1, 9]. The process initiates with the release of arachidonic acid from cell membranes by phospholipase A2 (PLA2), which is then converted into the unstable intermediate prostaglandin H2 (PGH2) by cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2) [4, 6]. The terminal step is catalyzed by prostaglandin E synthases (PGES), including the inducible microsomal PGES-1 (mPGES-1) and the constitutive mPGES-2 and cytosolic PGES (cPGES), which isomerize PGH2 into PGE2 [5, 7]. These enzymes are major therapeutic targets for inflammatory conditions and cancer, as PGE2 overproduction drives disease progression and immune evasion [8, 13]. While traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors are widely used to block this pathway, they carry risks of gastrointestinal and cardiovascular adverse effects [2, 10]. Consequently, current drug development efforts are focused on selective mPGES-1 inhibitors, which aim to suppress pathological PGE2 levels more specifically while maintaining the balance of other essential prostanoids [1, 12].

Other names

Prostaglandin E2 synthetic pathwayPGE2 biosynthesis pathwayCyclooxygenase-Prostaglandin E synthase pathwayEicosanoid biosynthetic enzymes

Inhibition of cyclooxygenase (COX-1/2) or prostaglandin E synthase (mPGES-1) activity to reduce the production of prostaglandin E2 from arachidonic acid.