The response of intracellular signaling and muscle-protein metabolism to nutrition and exercise

Abstract

In recent years, a body of literature examining the response of muscle-protein metabolism to exercise and nutrition has arisen. Developments in methods, especially stable isotopic tracer methodology, have allowed much information to be gathered in vivo in humans. The metabolic mechanism behind increased muscle mass requires that muscle-protein synthesis exceeds breakdown, i.e., net muscle-protein synthesis. Increased net muscle-protein balance may occur due to exercise, but net synthesis may occur only with the addition of nutrients, particularly a source of amino acids. The major impact of increased amino acid availability on net muscle-protein balance is due to stimulation of muscle-protein synthesis and less to inhibition of muscle-protein breakdown. Amino acids seem to stimulate muscle-protein synthesis, not only by mass action, i.e., providing substrate, but also as signals for initiation of protein synthesis. Stimulation of muscle-protein synthesis by amino acid ingestion may be linked to increased intracellular amino acid levels and/or to changing amino acid levels in the blood. Carbohydrate ingestion, most likely through the action of insulin, also may play a role in the response of muscle to exercise and nutrition. There is very little research in humans in vivo on the intracellular signaling that is linked to muscle-protein synthesis. It is clear that intracellular signaling responds to both insulin and amino acids, but the interactions with exercise are not well known; however, the details of the pathways have only just begun to be investigated, especially in humans. Delineation of these pathways is complicated, and there is little doubt that multiple intracellular signaling pathways with several levels of communication are involved in the hypertrophy process in response to nutrition and exercise. A systematic investigation of the relationship of the signaling to insulin and amino acids combined with exercise will provide important information, especially for populations vulnerable to muscle loss.