Interaction of metabolism of aspartate and inosine and energy state of malignant cells

1. Oxidation of glutamine in Ehrlich ascites-carcinoma cells results in a large accumulation of aspartate. 2. The addition of inosine causes a marked decrease in aspartate production from glutamine. This may be related to the resynthesis of AMP from aspartate and IMP, the latter being produced from inosine via the salvage pathway for purine nucleotides. In accordance with this assumption, a significant production of lactate was observed, which comes probably from the ribose moiety of inosine. Since lactate is known to inhibit production of aspartate from glutamine, this may explain the effect of inosine. 3. Addition of glutamine together with inosine increased cellular ATP content. This was not the case if glutamine or inosine was present separately or if inosine was added together with lactate, pyruvate or glucose. The effect did not occur if amino-oxyacetate, an inhibitor of transaminases, was added. These findings suggested again that production of aspartate is important for resynthesis of ATP from IMP via the purine nucleotide cycle. 4. If the cells were exposed to prolonged anaerobic incubation, addition of glutamine and inosine markedly increased O2 uptake and [ATP], suggesting the crucial importance of aspartate production by glutamine oxidation for the recovery of energy metabolism in the cells.