Alterations of Galactosaminyl- and Galactosyltransferases in Cultured Mammalian Cells and in Vivo
A large proportion of the reactions involved in the biosynthesis of cellular constituents are catalyzed by membrane-bound enzymes. A major group of these components is the sialoglycolipids known as gangliosides. These substances contain a common subunit called ceramide (N-acylsphingosine) to which carbohydrate chains are linked by their nonreducing ends. A homologous series of gangliosides is found in normal contact-inhibited cultured mouse cell lines containing 2–4 molecules of hexose and 1 or 2 molecules of N-acetylneuraminic acid (or N-glycolylneuraminic acid) (Figure 1). A larger series of gangliosides is present in normal human brain and the structures of these components are indicated in Figure 2. We have recently observed striking alterations in both of these patterns resulting from specific blocks in the synthesis of gangliosides. The agents which bring about these enzymatic defects in the cultured cells simultaneously cause tumorogenic transformation of the cells. In this chapter we shall examine the potential relevance of the altered ganglioside composition to neoplastic transformation of cells. We shall also indicate the pathological consequences of a particular block in ganglioside synthesis in a novel human metabolic disorder which has recently been identified.
KeywordsSarcoma Lactose Pyrene Galactose Butyrate
Unable to display preview. Download preview PDF.
- Basiligo, C., Renger, H. C., Burstin, S. J., and Toniolo, D., 1974, Host cell control of viral transformation, in:Control of Proliferation in Animal Cells (B. Clarkson and R. Baserga, eds.), Cold Spring Harbor, New York, pp. 167–176.Google Scholar
- Brady, R. O., and Mora, P. T., 1970, Alterations in ganglioside pattern and synthesis in SV-40 and polyoma virus-transformed mouse cell lines, Biochim. Biophys. Acta 218:308.Google Scholar
- Brady, R. O., Fishman, P. H., and Mora, P. T., 1973, Membrane components and enzymes in virally transformed cells, Fed. Proc. 32:192.Google Scholar
- Kaufman, B., Basu, S., and Roseman, S., 1967, Studies on the biosynthesis of gangliosides, in:Inborn Disorders of Sphigo lipid Metabolism (S. M. Aaronson and B. W. Volk, eds.), pp. 193–213, Pergamon Press, Oxford.Google Scholar
- Mora, P. T., Fishman, P. H., Bassin, R. H., Brady, R. O., and McFarland, V. W., 1973, Transformation of Swiss 3T3 cells by murine sarcoma virus is followed by a decrease in a glycolipid glycosyltransferase, Nature, 245:226.Google Scholar
- Sheinin, R., Onodera, K., Yogeeswaran, G., and Murray, R. K., 1971, Studies of components of the surface of normal and virus-transformed mouse cells, in: The Biology of Oncogenic Viruses (L. G. Silvestre, ed.), pp. 274–285, North Holland, Amsterdam.Google Scholar