Skeletal muscle glutamine transport, intramuscular glutamine concentration, and muscle-protein turnover

This article reviews work we have carried out to investigate (1) the transport mechanism responsible for the high distribution ratio of free glutamine commonly observed in skeletal muscle; (2) the fall in the distribution ratio that accompanies starvation, injury and chronic disease, whether directly involving muscle or not; and (3) the effect of modulation of intracellular free-glutamine concentration on protein synthesis and breakdown in skeletal muscle. We suggest that the results are consistent with the controlling role of the muscle membrane glutamine-sodium cotransporter in the regulation of the intracellular glutamine pool, the existence of pathophysiological mechanisms for the modulation of intramuscular glutamine and anabolic effects of glutamine in promoting protein synthesis, with a smaller effect in reducing protein breakdown. The mechanisms by which glutamine effects skeletal muscle protein turnover, and thus muscle protein balance, and the extent of the net flow of amino acids between the periphery and the viscera are unknown as yet, but the results suggest that modulation of transporter activity may offer the possibility of therapeutic intervention to reduce muscle wasting associated with injury and disease.