Prostaglandin E2 synthetic pathway (PGE2 pathway)

The Prostaglandin E2 (PGE2) synthetic pathway is a multi-step enzymatic cascade that converts arachidonic acid into PGE2, a key lipid mediator of inflammation and homeostasis (Source: StatPearls). The process is initiated by phospholipase A2, which releases arachidonic acid from cell membranes, followed by the action of cyclooxygenase enzymes (COX-1 and COX-2) to form the intermediate prostaglandin H2 (Source: PubMed). Finally, PGH2 is converted to PGE2 by specific prostaglandin E synthases, including the inducible microsomal prostaglandin E synthase-1 (mPGES-1), which is frequently upregulated during inflammatory responses (Source: UniProt). PGE2 signals through four G protein-coupled receptors (EP1-EP4) to modulate pain, fever, and vascular tone (Source: NIH). In clinical practice, this pathway is a primary target for nonsteroidal anti-inflammatory drugs (NSAIDs) and coxibs, which inhibit COX enzymes to reduce pain and inflammation (Source: PubChem). However, chronic inhibition of the pathway can lead to adverse effects such as gastrointestinal ulcers and cardiovascular complications due to the suppression of homeostatic prostanoids (Source: PubMed). Emerging therapeutic strategies aim to selectively inhibit mPGES-1 to reduce PGE2 levels without affecting other protective prostaglandins, potentially offering a safer alternative to traditional NSAIDs (Source: Peer-reviewed Journal).

Other names

Arachidonic acid-prostaglandin E2 cascadePGE2 biosynthesis pathwayCyclooxygenase-prostaglandin E synthase pathway

Inhibition of cyclooxygenase enzymes (COX-1 and COX-2) to prevent the conversion of arachidonic acid to prostaglandin H2, or inhibition of prostaglandin E synthases (mPGES-1) to prevent the conversion of PGH2 to PGE2.