Glutamine: an anaplerotic precursor.

There is an up to four-fold increase in the concentration of the tricarboxylic acid (TCA) cycle intermediates at the start of exercise. The rate of TCA cycle flux and, hence, oxidative metabolism may be limited by the concentration of the intermediates in the cycle. The dramatic decline in intramuscular glutamate at the start of exercise, in tandem with increased intramuscular alanine, suggests that glutamate is an important anaplerotic precursor. We hypothesized that oral glutamine might enhance the exercise-induced TCA cycle intermediate pool expansion. Indeed, a greater increase in the sum of muscle citrate, malate, fumarate, and succinate concentrations (approximately 85% total TCA intermediate pool) occurred at the start of exercise after ingestion of glutamine rather than of placebo or ornithine alpha-ketoglutarate. However, neither endurance capacity nor the degree of phosphocreatine depletion or lactate accumulation was altered. This suggests that TCA cycle intermediates do not limit flux through the cycle or that more intense exercise is required to show the limitation.