Specific objectives of this application are: (1) to determine the mechanism of how ethanolamine plasmalogens are synthesized from an intact alkyl phospholipid by a 1-alkyl desaturase, (2) to identify the factors that influence branchpoints and to identify the rate-limiting steps in the metabolic pathways for glycerolipids that determine membrane lipid composition with respect to the diacyl-, alkylacyl-, and alk-l-enylacyl- subclasses of phospholipids, and (3) to characterize the properties and to delineate the reaction mechanism and regulatory role of the enzymes that cleave the alkyl (Pte.H4-dependent alkyl monooxygenase) and alk-1-enyl (plasmalogenase) ether bonds in glycerolipids. The studies of the desaturase and the cleavage enzymes are expected to be done with purified preparations of the enzymes. Results of this work are expected to extend our basic understanding of the metabolism of lipids with ether-linked chains, including those phospholipids that are precursors of the alkylacetylated types (e.g., platelet activating factor) that exhibit potent biological activities. Information from these experiments are also expected to explain why ether lipids are characteristically elevated in most cancer cells and could shed light on their functional role in cell membranes.
