Ac-PTGS2 dimer oxidises DHA to 17(R)-Hp-DHA

Stable Identifier
R-HSA-9020261
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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Ac-PTGS2 dimer oxidises DHA to 17(R)-Hp-DHA
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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 is able to incorporate molecular oxygen into ω-3 fatty acid docosahexaenoic acid (DHA), present in inflammatory exudates, to form the 17(R) epimer 17(R)-hydroperoxy-docosahexaenoic acid (17(R)-Hp-DHA) (Serhan et al. 2002, Sun et al. 2007). The product can either be transformed into aspirin-triggered D-resolvins or aspirin-triggered protectin D1 (Serhan et al. 2015).
Literature References
PubMed ID Title Journal Year
17244615 Resolvin D1 and its aspirin-triggered 17R epimer. Stereochemical assignments, anti-inflammatory properties, and enzymatic inactivation

Serhan, CN, Campbell, E, Colgan, SP, Oh, SF, Petasis, NA, Gotlinger, K, Yang, R, Uddin, J, Sun, YP

J. Biol. Chem. 2007
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
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Output
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as an event of
Catalyst Activity

oxidoreductase activity, acting on single donors with incorporation of molecular 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 (GO:0016701)
Orthologous Events
Ac-PTGS2 dimer oxidises DHA to 17(R)-Hp-DHA (Bos taurus)
Ac-PTGS2 dimer oxidises DHA to 17(R)-Hp-DHA (Canis familiaris)
Ac-PTGS2 dimer oxidises DHA to 17(R)-Hp-DHA (Danio rerio)
Ac-PTGS2 dimer oxidises DHA to 17(R)-Hp-DHA (Gallus gallus)
Ac-PTGS2 dimer oxidises DHA to 17(R)-Hp-DHA (Mus musculus)
Ac-PTGS2 dimer oxidises DHA to 17(R)-Hp-DHA (Rattus norvegicus)
Ac-PTGS2 dimer oxidises DHA to 17(R)-Hp-DHA (Sus scrofa)
Ac-PTGS2 dimer oxidises DHA to 17(R)-Hp-DHA (Xenopus tropicalis)
Authored
Jassal, B  (2017-09-05)
Reviewed
Hansen, TV  (2018-02-21)
Created
Jassal, B  (2017-09-05)
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