Reactome | Ac-PTGS2 dimer oxidises EPA to 18(R)-HpEPE or 18(S)-HpEPE

Ac-PTGS2 dimer oxidises EPA to 18(R)-HpEPE or 18(S)-HpEPE

Stable Identifier

R-HSA-9018880

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

ReviewStatus

5/5

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Ac-PTGS2 dimer oxidises EPA to 18(R)-HpEPE or 18(S)-HpEPE

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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 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).

Literature References

PubMed ID	Title	Journal	Year
11034610	Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing Chiang, N, Colgan, SP, Serhan, CN, Brannon, J, Gronert, K, Clish, CB	J. Exp. Med.	2000
21206090	Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation Pillai, PS, Serhan, CN, Oh, SF, Yang, R, Recchiuti, A	J. Clin. Invest.	2011

Participants

Input

Output

18(S)-HpEPE, 18(R)-HpEPE [cytosol]

Participates

as an event of

Biosynthesis of EPA-derived SPMs (Homo sapiens)

Catalyst Activity

oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen of Ac-PTGS2 dimer [endoplasmic reticulum membrane]

Physical Entity

Ac-PTGS2 dimer [endoplasmic reticulum membrane] (Homo sapiens)

Activity

oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen (GO:0016702)

Orthologous Events

Ac-PTGS2 dimer oxidises EPA to 18(R)-HpEPE or 18(S)-HpEPE (Bos taurus)

Ac-PTGS2 dimer oxidises EPA to 18(R)-HpEPE or 18(S)-HpEPE (Canis familiaris)

Ac-PTGS2 dimer oxidises EPA to 18(R)-HpEPE or 18(S)-HpEPE (Danio rerio)

Ac-PTGS2 dimer oxidises EPA to 18(R)-HpEPE or 18(S)-HpEPE (Gallus gallus)

Ac-PTGS2 dimer oxidises EPA to 18(R)-HpEPE or 18(S)-HpEPE (Mus musculus)

Ac-PTGS2 dimer oxidises EPA to 18(R)-HpEPE or 18(S)-HpEPE (Rattus norvegicus)

Ac-PTGS2 dimer oxidises EPA to 18(R)-HpEPE or 18(S)-HpEPE (Sus scrofa)