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Coenzyme A thioester formation of 11- and 15-oxo-eicosatetraenoic acid.
- Source :
-
Prostaglandins & Other Lipid Mediators . May2017, Vol. 130, p1-7. 7p. - Publication Year :
- 2017
-
Abstract
- Release of arachidonic acid (AA) by cytoplasmic phospholipase A2 (cPLA2), followed by metabolism through cyclooxygenase-2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH), results in the formation of the eicosanoids 11-oxo- and 15-oxo-eicosatetraenoic acid (oxo-ETE). Both 11-oxo- and 15-oxo-ETE have been identified in human biospecimens but their function and further metabolism is poorly described. The oxo-ETEs contain an α,β-unsaturated ketone and a free carboxyclic acid, and thus may form Michael adducts with a nucleophile or a thioester with the free thiol of Coenzyme A (CoA). To examine the potential for eicosanoid-CoA formation, which has not previously been a metabolic route examined for this class of lipids, we applied a semi-targeted neutral loss scanning approach following arachidonic acid treatment in cell culture and detected inducible long-chain acyl-CoAs including a predominant AA-CoA peak. Interestingly, a series of AA-inducible acyl-CoAs at lower abundance but higher mass, likely corresponding to eicosanoid metabolites, was detected. Using a targeted LC–MS/MS approach we detected the formation of CoA thioesters of both 11-oxo- and 15-oxo-ETE and monitored the kinetics of their formation. Subsequently, we demonstrated that these acyl-CoA species undergo up to four double bond reductions. We confirmed the generation of 15-oxo-ETE-CoA in human platelets via LC-high resolution MS. Acyl-CoA thioesters of eicosanoids may provide a route to generate reducing equivalents, substrates for fatty acid oxidation, and substrates for acyl-transferases through cPLA2-dependent eicosanoid metabolism outside of the signaling contexts traditionally ascribed to eicosanoid metabolites. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10988823
- Volume :
- 130
- Database :
- Academic Search Index
- Journal :
- Prostaglandins & Other Lipid Mediators
- Publication Type :
- Academic Journal
- Accession number :
- 123217797
- Full Text :
- https://doi.org/10.1016/j.prostaglandins.2017.02.004