Glutamate Oxidation in 6C3HED Lymphoma: Effects of L-Asparaginase on Sensitive and Resistant Lines

Abstract

L-Asparaginase (EC 3.5.1.1) inhibited respiration in sensitive, but not resistant, lines of murine lymphoma 6C3HED. Glucose, in these tumor lines, was principally converted to lactate, and very little was oxidized in the citric acid cycle or hexose monophosphate shunt. The cells derived 70-80% of their respiratory CO(2) from glutamine or glutamate. Asparaginase had no effect on the pattern of glucose utilization. The differential effect on oxygen consumption may result from the absence of asparagine synthetase in sensitive cells. Respiration may be inhibited by accumulation of the aspartate, the product of glutamate oxidation. Resistant lymphoma cells remove aspartate by converting it to asparagine. Sensitive cells, which lack asparagine synthetase, cannot make asparagine.