The proposed investigations are a continuation of studies on the distribution, chemistry, and intermediary metabolism of sphingolipids. These studies will focus largely in four specific areas of effort, biosynthesis of sphingolipid bases, development of improved chromatographic procedures for the analysis of carbohydrates derived from glycosphingolipids and glycoproteins, isolation and characterization of lysosomal glycosidases, and control of the metabolism of cell surface glycosphingolipids in synchronized cultures of normal and transformed cells. Although substantial progress has been made in these areas during the past several years, much remains to be learned about the nature of sphingosine synthetase and the stereochemical mechanism of the reaction catalyzed by this microsomal enzyme; the composition of glycosphingolipids on the outer surface of cells; the substrate specificities of lysosomal glycosidases, the nature of hydrophobic sites on these enzymes, and chemical differences between multiple forms; and factors that regulate cell-cycle specific synthesis and catabolism of membrane glycosphingolipids that are associated with phenomena in eukaryotic cells such as contact inhibition, cell-cell adhesion, cell surface receptors, and malignant transformation. In addition to these projects, expertise for the isolation, quantitation and characterization of sphingolipids and for the assay of lysosomal glycosidases will remain available for collaboration with clinicians on potential inborn errors of sphingolipid metabolism.
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