Prostaglandin-E synthase 1 (PTGES)

Prostaglandin-E synthase 1 (PTGES, or mPGES-1) is a terminal enzyme in the biosynthetic pathway leading to prostaglandin E2 (PGE2), the principal protective and regulatory prostaglandin in the gastric mucosa. PGE2 is synthesized from arachidonic acid through the actions of phospholipase A2, cyclooxygenases (COX-1 and COX-2), and finally PTGES. In gastric mucosa, PGE2 modulates mucosal protection by stimulating the secretion of mucus and bicarbonate, inhibiting gastric acid secretion, and mediating anti-inflammatory effects. The clinical importance of this pathway is reflected in the fact that inhibition of PGE2 synthesis—by NSAIDs—can cause peptic ulcer disease and GI bleeding. Therapeutic strategies focus on modulating this pathway by either mimicking PGE2’s action (with analogs) or inhibiting PTGES or COX enzymes. The process is often dysregulated in various diseases, including ulcers, inflammation, and possibly cancer. The query refers to a process (“PGE2 synthesis in gastric mucosa”), not a molecule. The canonical molecular target in this context is Prostaglandin-E synthase 1 (PTGES/mPGES-1), the enzyme catalyzing the final step of PGE2 biosynthesis. “Prostaglandin E2” itself is a product and may act as a drug (dinoprostone), but the principal molecular target for synthesis is the synthase enzyme.

Other names

microsomal prostaglandin-E synthase 1 (mPGES-1)Prostaglandin E synthasePTGESProstaglandin-E synthase 2 (mPGES-2; less prominent in gastric mucosa)Cytosolic prostaglandin-E synthase (cPGES; not dominant in gastric mucosa)

Inhibition of prostaglandin-E synthase (direct inhibition of PTGES, blocking PGE2 synthesis); Inhibition of cyclooxygenase enzymes (COX-1/COX-2 inhibitors lower all prostaglandins, including PGE2); Receptor agonism (PGE2 analogs stimulate EP receptors; mechanism is not enzyme inhibition but receptor activation)