Arachidonic acid (AA) and linoleic acid (LA) are two of the most abundant ?-6 fatty acids found in the lipid bilayer, and are important precursors to many inflammatory signaling molecules.  AA is metabolized to prostaglandin H2 through the cyclooxygenase-2 (COX-2) pathway, and LA is metabolized to hydroxyoctadecadienoic acids.  Both metabolism pathways also produce a range of a,�-unsaturated carbonyls, which are capable of reacting with nucleophilic amino acid side chains, changing protein function.  We have synthesized an ?-alkynylated arachidonic acid (aAA) and linoleic acid (aLA) to help us map endogenous protein adduction in RAW 264.7 mouse macrophages. aAA is incorporated and released from the lipid bilayer similarly to AA, but exhibits a different metabolite profile and kinetics than AA when reacted with COX-2.  This appears to result from an altered substrate orientation in the enzyme active site during catalysis.

Characterization of cyclooxygenase-2 metabolism of [omega]-alkynyl arachidonic and linoleic acid, and their use as tools to understand inflammation related protein adduction

244th National Meeting (2012)

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