Addition of
glucose to Ehrlich-Landschütz
ascites tumour cells preincubated for 30-60 min in
phosphate-buffered Krebs-Ringer
salt solution ("starved cells") resulted within 1-2 min in an approx. 90% decline of their
ATP content and a massive accumulation of
fructose 1,6-bisphosphate. These alterations, which took place under both aerobic and anaerobic conditions, were followed by a gradual spontaneous recovery with restoration of normal
ATP and
fructose 1,6-bisphosphate values. The transient derangement of the energy metabolism after
glucose addition to starved
ascites tumour cells by preventable by simultaneous addition of
pyruvate or
2-oxobutyrate, or by preincubating the cells in the presence of
glucose. The protective effect of
pyruvate was duplicated by addition of
phenazine methosulphate or NAD+ to the incubation medium. The data seem to warrant the conclusion that the
glucose-induced
ATP depletion is determined by a blockade of glycolysis at the stage of
glyceraldehyde phosphate dehydrogenase caused by the failure of the cells to oxidize the
NADH produced in the same reaction. The continued unrestrained action of
6-phosphofructokinase results in accumulation of
fructose 1,6-bisphosphate, which constitutes a trap for the high-energy
phosphate bonds of
ATP. The primary metabolic disturbance appears to consist of a transient inhibition of
pyruvate kinase with the resultant inability of the cells to maintain an unimpaired supply of
pyruvate, as required for the
lactate dehydrogenase-mediated oxidation of
NADH. The regulatory mechanism underlying this phenomenon is discussed.