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 neutrophils can be acetylated by ASA, which now switches to mediate biosynthesis of precursors of endogenous antiinflammatory mediators. Ac-PTGS2 dimer is able to incorporate molecular oxygen into eicosapentaenoic acid (EPA) to form the stereoisomers 18(S)- and 18(R)-hydroperoxy-eicosapentaenoic acid (18(S)- and 18(R)-HpEPE respectively) (Serhan et al. 2000, Oh et al. 2011).
Chiang, N, Colgan, SP, Serhan, CN, Brannon, J, Gronert, K, Clish, CB
Pillai, PS, Serhan, CN, Oh, SF, Yang, R, Recchiuti, A
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen of Ac-PTGS2 dimer [endoplasmic reticulum membrane]
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