Glutamate-Mediated Respiration in Tumors2

Abstract

Fluoropyruvate (FP), a pyruvate analog, and vinblastine (VLB), an oncolytîc vinca alkaloid, inhibited oxygen (O2) uptake in sarcoma 180 and 3 Morris hepatoma lines. Glutamate, which inhibits the oncolytic effects of VLB, prevented the effect on O2 uptake when added simultaneously with VLB. Glutamate also mitigated the effects of FP at low concentrations (≤5 mM), concentrations which inhibit pyruvate oxidation and reduction. At higher concentrations where FP also inhibited α-ketogIutarate oxidation, glutamate failed to prevent inhibition of O2 consumption. VLB did not inhibit respiration of normal mouse liver or spleen, and FP inhibition of respiration of mouse liver, spleen, and skeletal muscle was not reversed by glutamate. These data suggest that glutamate may be oxidized in place of pyruvate in the citric acid cycle of these tumors and is vital to their respiration.