Studies on respiration and glycolysis in transplanted hepatic tumors of the rat.

In a continuation of studies on glycolytic and respiratory interrelationships in a series of rat hepatomas ranging widely in growth rate and degree of differentiation, whole, fortified homogenates of these tissues were incubated at 28°Cin the presence of frue tose-1,6-diphosphate (FDP), 2-deoxyglucose (2-DG), and exogenous hexokinase; respiration, lactate forma tion, and uptake of 2-DG were measured. Preliminary studies with this model system established that uptake of 2-DG was a valid measure of ATP formation. On the assumption that each mole of lactate formed from FDP leads to production of 2 moles of ATP via phosphoglycerate kinase and pyruvate kinase, glycolytic phosphorylation was estimated as twice that of lactate, and respiratory phosphorylation was calculated as the difference between total ATP and glycolytic ATP formation. Without exogenous substrate, respiration was high in homoge nates of well-differentiated tumors, and low in those of poorly differentiated tumors. In both tumor types respiration was coupled with ATP formation, yielding P/0 ratios of 1 to 2. Addition of FDP to liver homogenates resulted in moderate lactate and glycolytic ATP formation, the latter being formed largely at the expense of respiratory phosphorylation. In ho mogenates of well-differentiated tumors, lactate formation and glycolytic phosphorylation were low, and neither respiration nor respiratory phosphorylation was decreased. In contrast, ho mogenates of the poorly differentiated hepatomas exhibited