Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism

Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops similar to 40-80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained ( T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption ((V)over doto(2peak)) in the T thigh was greater than that in the UT thigh (P < 0.05); (V)over doto(2peak) was not different between the T and UT thighs with glutamate infusion. Peak exercise under control conditions revealed a greater glutamate uptake in the T thigh compared with rest (7.3 +/- 3.7 vs. 1.0 +/- 0.1 mu mol . min(-1) . kg wet wt(-1), P < 0.05) without increase in TCA cycle intermediates. In the UT thigh, peak exercise ( vs. rest) induced an increase in fumarate (0.33 +/- 0.07 vs. 0.02 +/- 0.01 mmol/kg dry wt (dw), P < 0.05) and malate (2.2 +/- 0.4 vs. 0.5 +/- 0.03 mmol/kg dw, P < 0.05) and a decrease in 2-oxoglutarate (12.2 +/- 1.6 vs. 32.4 +/- 6.8 mu mol/kg dw, P < 0.05). Overall, glutamate infusion increased arterial glutamate (P < 0.05) and maintained this increase. Glutamate infusion coincided with elevated fumarate and malate (P < 0.05) and decreased 2-oxoglutarate (P < 0.05) at peak exercise relative to rest in the T thigh; there were no further changes in the UT thigh. Although glutamate may have a role in the expansion of the TCA cycle, glutamate and TCA cycle intermediates do not directly affect (V)over doto(2peak) in either trained or untrained muscle.