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

Stable Identifier
R-HSA-9027627
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, endoplasmic reticulum membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Ac-PTGS2 dimer oxidises DHA to 17-HDHA (macrophages)
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
Participants
Input
Output
Participates
as an event of
Catalyst Activity

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

Physical Entity
Ac-PTGS2 dimer [endoplasmic reticulum membrane] (Homo sapiens)
Activity
arachidonate 15-lipoxygenase activity (GO:0050473)
Orthologous Events
Ac-PTGS2 dimer oxidises DHA to 17-HDHA (macrophages) (Bos taurus)
Ac-PTGS2 dimer oxidises DHA to 17-HDHA (macrophages) (Canis familiaris)
Ac-PTGS2 dimer oxidises DHA to 17-HDHA (macrophages) (Danio rerio)
Ac-PTGS2 dimer oxidises DHA to 17-HDHA (macrophages) (Gallus gallus)
Ac-PTGS2 dimer oxidises DHA to 17-HDHA (macrophages) (Mus musculus)
Ac-PTGS2 dimer oxidises DHA to 17-HDHA (macrophages) (Rattus norvegicus)
Ac-PTGS2 dimer oxidises DHA to 17-HDHA (macrophages) (Sus scrofa)
Ac-PTGS2 dimer oxidises DHA to 17-HDHA (macrophages) (Xenopus tropicalis)
Authored
Jassal, B  (2017-09-05)
Reviewed
Hansen, TV  (2018-02-21)
Created
Jassal, B  (2017-11-03)
Cite Us!