The overall objective of the proposed research program is to understand phospholipid metabolism in synaptosomes and microsomes isolated from the mammalian brain tissue. Special emphasis will be on metabolism of the non-polar side chains of the phospholipid molecules. Synaptosomes and microsomes isolated from mouse, ox, and monkey brain will be incubated with labeled long chain fatty acids (16:0, 18:0, 18:1, 18:2, 18:3 and 20:4) in a system containing ATP, CoA and Mg ions. Optimal conditions for incubation with the cofactors will be established with each subcellular fraction. Incorporation of radioactivity into the phosphoglycerides (phosphatidic acids, diacyl-sn- glycerophosphorylcholine, diacyl-sn-glycerophosphorylethanolamine, diacyl-sn-glycerophosphorylserine, diacyl-sn-glycerophosphoryl inositol and alkenylacyl-sn-glycerophosphorylethanolamine) and neutral glycerides (diacylglycerol, triacylglycerol and cholesterolester) will be examined after thin-layer chromatographic separations. Acyl group composition of phosphoglycerides will be analyzed by gas-liquid chromatography. Purity of subcellular membranes will be evaluated by electron microscopic examination, assays of marker enzymes, analysis of the membrane lipids and separation of the membrane proteins by SDS-gel electrophoresis. Metabolic activity of the membrane phospholipids will be investigated with regard to effects of neurohormones, psychoactive drugs, and in animals afflicted by age, deficient diets and other neurological abnormalities. It is anticipated that the investigation will provide valuable information correlating synaptosomal lipid metabolism to important CNS functions such as synaptic transmission, active cation transport and other processes that may modify CNS functions.