Pathways of glycogen synthesis in Novikoff ascites-hepatoma cells.

Affinity of glucose, fructose and mannose for tumour hexokinase and their rates of phosphorylation at saturation concentration have been correlated with rates of glycogen synthesis by intact tumour cells at different concentrations of the three substrates. Competition experiments with one sugar labelled and the other sugar unlabelled indicate inhibition of glycogen synthesis by the sugar with a low K(m) for hexokinase. Glycogen synthesis from glucose 1-phosphate in aged cells and from nucleoside in freshly prepared cells is stimulated by fructose and inhibited by glucose. The decrease in glycogen formation from glucose 1-phosphate by oligomycin is partially overcome by increased fructose concentrations. These results are explained by an activation of alpha-glucan phosphorylase by fructose and an inhibition of this enzyme by glucose. It is suggested that differences in localization of glucose 6-phosphate, available to the intact cell in various ways, determine its transformation into glycogen by either the UDP-glucose-alpha-glucan glucosyltransferase reaction or by the alpha-glucan phosphorylase reaction.