The major objective of the proposed research is to evaluate the relative contribution of glycerol-3-phosphate pathway and acyl dihydroxyacetone phosphate pathway to the formation of phosphatidic acid in brain and liver. The role of acyl dihydroxyacetone phosphate and alkyl dihydroxyacetone phosphate in the metabolism of glycerolipids and glycerol-ether lipids will be studied. The properties of the individual enzymes of the acyl dihydroxyacetone phosphate pathway will be investigated and attempts will be made to solubilize and purify these enzymes. Further studies will be made on the mechanism of induction of glycerophosphate acyltransferase and dihydroxyacetone phosphate acyltransferase (two key enzymes for glycerolipid biosynthesis) in liver by hypolipidemic drugs (e.g. clofibrate). Different analogs of acyl dihydroxy-acetone phosphate will be synthesized to test their possible use as inhibitors to some of the key enzymatic reactions. The metabolism of the """"""""Platelet Activating Factor"""""""", i.e. 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine in brain and liver and its physiological role in brain will be investigated.
