Prostaglandin E2 biosynthetic pathway (PGE2 biosynthesis)

Prostaglandin E2 (PGE2) biosynthesis is a critical multi-enzyme metabolic pathway responsible for generating one of the primary lipid mediators of inflammation and physiological homeostasis. The process initiates with the liberation of arachidonic acid from cellular membranes by phospholipase A2, followed by the conversion of this precursor into the intermediate prostaglandin H2 (PGH2) by cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2) [1, 2]. The terminal step involves the isomerization of PGH2 into PGE2, catalyzed by specific PGE synthases, most notably the inducible microsomal isoform mPGES-1 [3, 5]. Overproduction of PGE2 is a hallmark of many diseases, including rheumatoid arthritis, osteoarthritis, and various cancers, where it drives pain, fever, angiogenesis, and immune evasion [4, 11]. While traditional non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and naproxen inhibit PGE2 production by targeting COX enzymes, they also suppress other beneficial prostanoids, leading to side effects. Consequently, modern therapeutic efforts are focused on selective mPGES-1 inhibitors, such as LY3023703, which aim to specifically block PGE2 biosynthesis without disrupting the global prostanoid profile [5, 11]. Citations: [1] Taylor & Francis (2009), 10.1517/13543770902997928; [2] Yang et al. (2019), PMC6533036; [3] Murakami et al. (2000), J Biol Chem 275:32783-32792; [4] MDPI (2021), 10.3390/cancers13050965; [5] Koeberle & Werz (2015), 10.1021/jm5011614; [11] Bergqvist (2019), CORE 215309624.

Other names

PGE2 synthesisProstaglandin E2 productionArachidonic acid-PGE2 cascadeCOX-mPGES-1 axisBiosynthesis of dinoprostone

Inhibition of cyclooxygenase enzymes (COX-1 and COX-2) or terminal prostaglandin E synthases (specifically mPGES-1) to reduce the enzymatic production of prostaglandin E2 from arachidonic acid.