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.
KeywordsMouse Cell Line Glycosyltransferase Activity Murine Sarcoma Virus Sialyltransferase Activity Ganglioside Pattern
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