As part of a program to elucidate some of the biochemical features and metabolic interrelationships of nervous system lipids, under normal and abnormal conditions, aspects of the metabolism and, insofar as feasible, the functions of glycosphingolipids are to be investigated. In particular, the involvement of these compounds in differentiation phenomena and membrane perturbation will be examined. The lipid patterns of transformed astrocytes and neuroblastoma which can be grown in cell culture will be determined and their neutral glycolipid and ganglioside composition and biosynthetic capability evaluated. Changes in patterns and metabolism of glycolipids, induced by conditions favoring the formation of new membranes or by the addition of drugs which act on the nervous system, such as tranquilizers, neurotransmitters and local anesthetics, will be investigated in intact cells, subcellular membranes and organelles of suitable clones, and of brain tissue. The studies will include the rigorous chemical identification of the products of biosynthetic reactions catalyzed by glycosyltransferases. This is to be achieved by establishing the nature of the glycosidic linkages between acceptor lipids of high specific radioactivity and the newly attached glycosyl units, utilizing chromatographic separation and identification of the permethylated carbohydrate residues. BIBLIOGRAPHIC REFERENCES: Stoffyn, A., Stoffyn, P. and Hauser, G. Structure of trihexosylceramide biosynthesized in vitro by rat kidney galactosyltranserase. Biochem. Biophys. Acta 360, 174-178 (1974). Hauser, G., Eichberg, J. and Shein, H. M. Lipid composition of experimental astrocytomas originating from transformed rat and hamster astrocyte cultures.