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Journal article
Coenzyme A thioester formation of 11- and 15-oxo-eicosatetraenoic acid
Prostaglandins & other lipid mediators, Vol.130, pp.1-7
May 2017
PMCID: PMC5446925
PMID: 28238887
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Coenzyme A thioester formation of 11- and 15-oxo-eicosatetraenoic acid
- Creators
- Clementina Mesaros - Penn SRP and Center for Excellence in Environmental Toxicology, Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, United States.Alejandro D Arroyo - Penn SRP and Center for Excellence in Environmental Toxicology, Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, United States.Ian A Blair - Penn SRP and Center for Excellence in Environmental Toxicology, Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, United States.Nathaniel W Snyder - Drexel University
- Publication Details
- Prostaglandins & other lipid mediators, Vol.130, pp.1-7
- Publisher
- Elsevier
- Grant note
- P42 ES023720 / NIEHS NIH HHS U54 HL117798 / NHLBI NIH HHS T32 GM008076 / NIGMS NIH HHS P30 ES013508 / NIEHS NIH HHS R21 HD087866 / NICHD NIH HHS P30 CA016520 / NCI NIH HHS R03 CA211820 / NCI NIH HHS K22 ES026235 / NIEHS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Identifiers
- 991019167624504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology