The objectives of the project encompass five principal areas. The first is the production of 14C-labeled glucocerebroside, 14C-labeled sphingomyelin, and 14C-labeled ceramidetrihexosidase for use as diagnostic reagents for the identification of patients and detection of carriers of Gaucher's disease, Niemann-Pick disease and Fabry's disease, respectively. Second, these radioactive sphingolipids are required to monitor the activity of enzymes for use in clinical therapy trials. The third objective is to develop novel sphingolipids that can be tagged with fluorescent dyes so that their cellular and subcellular distribution can be traced. The fourth objective is to synthesize non-metabolizable analogs of sphingolipids for animal and tissue models of human lipid storage disorders. The fifth objective is to synthesize more complex sphingolipids called gangliosides so that their metabolism can be examined in normal and neoplastic tissues.
