Rate-limiting Factors in Glycolysis and Transport of Inorganic Phosphate in DBAH₁ Tumor, DBAG Tumor, Novikoff Hepatoma, and Novikoff Ascites Tumor¹ Free

In DBAH₁ tumor, DBAG tumor, and Novikoff hepatoma, both aerobic and anaerobic glycolysis were stimulated by increasing the glucose concentration from 0.5 to 5 mm. Therefore, it was concluded that the availability of intracellular glucose was a rate-limiting factor for glycolysis. In these 3 tumors, the difference between the rates of aerobic and anaerobic lactate production was primarily due to a more severe inhibition of P-fructokinase³ activity under aerobic conditions. Thus, P-fructokinase was at least partially responsible for the Pasteur effect. In addition, the inhibition of P-fructokinase resulted in an accumulation of glucose-6-P, which then inhibited hexokinase activity.

In Novikoff ascites tumor cells, after the addition of glucose, rate-limiting factors for glycolysis and the levels of intracellular intermediates were found to change continuously with the time of incubation. Factors responsible for the Pasteur effect also change with the length of incubation. Under anaerobic conditions, striking parallism between the rate of lactate production and the level of intracellular P_i concentration were observed at every time interval.

In all 4 types of tumors, P_i transport can be facilitated by both the glycolytic and the respiratory energy. This appears to be a unique feature of all tumors studied so far, since normal cells examined to date can use only respiratory energy for P_i transport.