Ac-PTGS2 dimer oxidises DHA to 17-HDHA (macrophages)

Stable Identifier
Reaction [transition]
Homo sapiens
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Normally, cyclooxygenases (COX) carry out stereospecific oxygenation of arachidonic acid to generate prostaglandins. When treated with aspirin (acetylsalicylic acid, ASA), dimeric cyclooxygenase 2 (COX2, PTGS2 dimer) can be acetylated. ASA covalently modifies PTGS2 by acetylating a serine residue at position 530 within the cyclooxygenase active site (Lucido et al. 2016). Acetylated PTGS2 dimer (Ac-PTGS2 dimer) changes the oxygenation stereospecificity towards its substrates, perhaps by steric shielding effects (Tosco 2013), producing a shift in lipid mediator production. Ac-PTGS2 dimer expressed in macrophages can be acetylated by ASA, which enables this form to mediate the biosynthesis of precursors of endogenous anti-inflammatory mediators. Ac-PTGS2 dimer is able to incorporate molecular oxygen into ω-3 fatty acid docosahexaenoic acid (DHA), to form 17-hydroxy-docosahexaenoic acid (17-HDHA) (Serhan et al. 2002, Groeger et al. 2010).
Literature References
PubMed ID Title Journal Year
12391014 Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals

Gronert, K, Serhan, CN, Devchand, PR, Colgan, SP, Hong, S, Mirick, G, Moussignac, RL

J. Exp. Med. 2002
20436486 Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids

Cipollina, C, Schopfer, FJ, Cole, MP, Rudolph, V, Freeman, BA, Groeger, AL, Rudolph, TK, Bonacci, G, Woodcock, SR

Nat. Chem. Biol. 2010
Catalyst Activity

arachidonate 15-lipoxygenase activity of Ac-PTGS2 dimer [endoplasmic reticulum membrane]

Orthologous Events
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