Inhibition of Glycolysis and Interference With Protein Synthesis in Hepatoma Cells

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Abstract
Ascites hepatoma cells grown in Wistar rats were incubated anaerobically in the absence of glucose or in the presence of both glucose and D(+)glucosamine, or monoiodoacetate, or NADH, which interfered with glycolysis at different steps and with different mechanisms: Under all these conditions the incorporation of amino acids into the proteins of hepatoma cells was severely reduced without any clear relationship to the degree of inhibition of glycolysis. The pastmitochondrial supernatants showed defective incorporation only when obtained from cells incubated in the absence of glucose or in the presence of monoiodoacetate; inhibition of glycolysis by glucosamine and NADH did not seem to affect the subcellular basis for protein synthesis. When present, the defect of the postmitochondrial supernatants was due to deficient activity of the cell sap (monoiodoacetate and absence of glucose) and to disaggregation and reduced functional capacity of the palysomes (absence of glucose). The results suggested that the effects of the inhibition of glycolysis on protein synthesis and on the integrity of the protein-synthesizing machinery—which were primarily due to the depletion of the energy stores—might have been modified by the particular mechanism of action of the inhibitor and by the way low levels of ATP were reached in the cell.