This proposal examines the role of arachidonic acid containing ether phospholipids in platelet function. The major focus of the proposal is to study regulation and properties of (1) platelet transacylase, responsible for incorporation of arachidonic acid into ether phospholipids and (2) platelet phospholipase A2, liberating esterified arachidonate from phospholipids for subsequent transformation to biologically active metabolites. The major goal of the proposal is to explore the control and functional significance of the metabolism of arachidonic acid in ether phospholipids in human platelets. Major techniques will include methods for purification and analysis of membrane-associated enzymes (detergent solubilization, column chromatography, electrophoresis) and methods for resolution and analysis of lipid mixtures (thin layer and high performance liquid chromatography). These studies will (1) provide insight into biochemical and functional properties of enzymes involved in production of biologically active compounds (eicosanoids and platelet activating factor), (2) elucidate the biological role(s) of ether phospholipids and (3) further the knowledge of platelet function and involvement of platelets in hemorrhagic and thrombotic diseases.
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