Glycerophospholipids in the brain include diacyl, alkenylacyl (plasmalogen), and alkylacyl types with many molecular species of each. Their turnover is mediated by several different lipases and phospholipases. Diacyl and monoacylglycerol lipases, phospholipase A2, and plasmalogenase will be purified, characterized, and utilized for antibody production. The antibodies will be used for further purification and for cytochemical localization. The influences of Ca2+ and lipomodulin on these lipases in normal and ischemic brains and the correlation of lipid peroxidation with activation of lipases during ischemia will be examined. The general objective is to determine the role of these lipases in the metabolism of glycerophospholipids in normal and ischemic brain. The rates of synthesis and turnover are different for different molecular species of glycerophospholipids. These rates will be compared with different precursors with emphasis on polyunsaturated fatty acids. Information on the turnover of polyunsaturated molecular species from inositol glycerophospholipids in required for understanding the activation of protein kinase C by activation of some receptors. Methods for the separation of intact plasmalogens from the corresponding diacyl compounds are being developed. This will be valuable for the study of plasmalogen synthesis. The metabolic pathway for the very rapid synthesis of choline plasmalogens will be sought with (3H)fatty alcohols as a quite specific precursor for alkyl and alkenyl groups. The possible pathways include those involving methylation, base-exchange reactions, and CDPcholine. The long-term objective is to discover the neurobiological function of plasmalogens and their polyunsaturated fatty acids.
