Studies of the biosynthesis and metabolism of carnitine in fungal and mammalian systems will continue. We have discovered the occurrence of lipid bound forms of lysine and methylated lysine metabolites following incubation of lysine in a rat liver slice system. Such metabolites, likely phosphatides, will be characterized and will be studied in appropriate biological systems related to carnitine biosynthesis or function. For example, conditions for the epsilon-N-methylation of lipid-bound lysine to form the corresponding trimethyllysine derivative will be sought in rat liver. The metabolism of gamma-N-trimethylaminobutan-1-ol, a homologue of choline, deriving from a branch point in carnitine biogenesis in Neurospora, will be studied in relation to lipid metabolism in Neurospora and the rat. Part II of the proposal will seek to elucidate the biochemical mechanism by which carnitine is transported from its site of synthesis to its site of action. Preliminary evidence indicates the presence of binding proteins in rat liver, plasma, cardiac muscle, skeletal muscle, and epididymis. These binding proteins will be isolated employing contemporary techniques of protein fractionation and characterized. Utilizing whole organ perfusion techniques, we will study the nutritional, biochemical and physiological factors controlling carnitine uptake by the working heart, the hind limb and the epididymis. The long term goal of the proposed research is to develop at the biochemical level an understanding of carnitine metabolism and its control. Such knowledge may have an application to abnormal carnitine metabolism that has been observed in certain disease states.
NIH ExPorter
NIH ExPorter