The Importance of Glutamate in Skeletal Muscle Metabolism Under Differrent Exercise Conditions

Abstract

THE IMPORTANCE OF GLUTAMATE IN SKELETAL MUSCLE METABOLISM UNDER DIFFERENT EXERCISE CONDITIONS Marina Mourtzakis Advisor: University of Guelph, 2004 Dr. T. E. Graham The tricarboxylic acid (TCA) cycle provides a central process for not only fat and carbohydrate pathways to merge but also for amino acids to integrate and play a putative role in regulating oxidative metabolism. Muscle glutamate is a central amino acid for all transamination reactions that integrate with the TCA cycle. However, at the onset of exercise muscle glutamate decreases despite a constant uptake from the circulation. This thesis investigated whether: 1) glutamate affects metabolic homeostasis in skeletal muscle and potential tissue interactions, 2) alterations in glutamate availability impose changes on oxidative metabolism, and 3) whether the interactions between glutamate and other amino acids impact on oxidative metabolism. The first study examined whether glutamate affects oxidative metabolism during prolonged exercise since pyruvate flux decreases under these conditions. Muscle biopsies and direct Fick measurements revealed that the largest net exchanges in glutamate and alanine occurred in the first hour of exercise while glutamate was consistently taken up for the rest of exercise. Pyruvate flux remained constant implying that it may not affect glutamate metabolism. The second study examined whether increased glutamate availability via glutamate ingestion would perturb oxidative metabolism. With increased circulating glutamate, pulmonary VO2 was elevated during moderate cycling and the proportions of nitrogen sources released were altered. The final study isolated endurance training to the quadriceps muscle of one thigh for 5 weeks while the other thigh remained untrained. Following training, each thigh underwent maximal work tests. Direct Fick measurements and muscle biopsies were obtained from each thigh at rest and maximal work rate during control and glutamate conditions. Muscle glutamate was not different between thighs at rest or during exercise under either conditions. However, glutamate uptake was increased with glutamate infusion compared to control. Training enhanced VO2peak, attenuated the increase in fumarate and malate, and lessened the decrease in 2-oxoglutarate. In contrast, glutamate administration resulted in ~20% and ~50% decreased muscle VO2peak and 2-oxoglutarate levels, respectively, while enhancing fumarate and malate concentrations in the trained thigh only. Collectively, these results suggest that alterations in glutamate availability can impact the regulation of oxidative energy provision in human skeletal muscle.