Prostaglandin-endoperoxide synthase peroxidase site (COX peroxidase site) (COX POX site)

The peroxidase site of Prostaglandin-endoperoxide synthase 1 and 2 (COX-1 and COX-2) is a distinct catalytic center responsible for the reduction of prostaglandin G2 (PGG2) to prostaglandin H2 (PGH2) [1]. This site contains a heme cofactor (protoporphyrin IX) that undergoes a two-electron oxidation by PGG2 to form an intermediate ferryl-oxo-heme radical, which then abstracts an electron from a nearby tyrosine residue to initiate the cyclooxygenase reaction [2]. Unlike the cyclooxygenase site, which is the primary target of traditional nonsteroidal anti-inflammatory drugs (NSAIDs), the peroxidase site is sensitive to reducing agents and phenolic compounds [3]. Drugs such as acetaminophen (paracetamol) and metamizole are believed to exert their analgesic and antipyretic effects by acting as reducing cosubstrates for the peroxidase site, thereby neutralizing the oxidizing environment and lowering the peroxide tone required for enzyme activation [1][4]. This mechanism is particularly effective in environments with low peroxide concentrations, such as the central nervous system, explaining the tissue-specific activity of these drugs [2]. Targeting the peroxidase site provides a therapeutic pathway to manage pain and fever while potentially avoiding the gastrointestinal and platelet-related side effects associated with direct cyclooxygenase inhibition [5].

Other names

Prostaglandin G2 peroxidase siteCyclooxygenase peroxidase active siteProstaglandin H synthase peroxidase siteHeme-dependent peroxidase site of COXCOX-1/COX-2 peroxidase site

Acts as a reducing agent or competitive inhibitor of the peroxidase reaction, thereby reducing the ferryl-oxo-heme radical and lowering the peroxide tone necessary for cyclooxygenase activation [1][2].