It is the goal of this proposal to investigate the general hypothesis that both the rates of protein breakdown and amino acid transport directly control the rate of protein synthesis after exercise by means of supplying free amino acids to the intracellular pool. In order to quantify the rates of muscle protein synthesis, breakdown and transmembrane transport of amino acids in human volunteers, a new model will be used that involves the use of tracers of amino acids labeled with stable isotopes and the measurement of arterial-venous differences and intracellular free amino acid enrichments and concentrations. In addition, the model-derived data will be confirmed by the fundamentally independent determination of the muscle fractional synthetic rate, as calculated by the traditional technique, and a novel approach to quantify the fractional breakdown rate. The effect of protein breakdown on protein synthesis will be assessed by comparing the responses to concentric verses eccentric exercise, because eccentric exercise will cause a greater rate of muscle protein damage, and thus protein degradation. Further, the responses of trained verses untrained subjects will be determined because muscle damage and protein breakdown after eccentric exercise will be less in trained subjects. We will also investigate the role of increased delivery of amino acids after exercise by decreasing post-exercise blood flow to the resting rate. Further, we will pharmacologically increase the resting leg blood flow to the post-exercise rate. Finally, the interactive effects of arterial amino acid concentration and muscle blood flow after exercise will be assessed by the infusion of amino acids into the leg with reduced blood flow so that the product of amino acid concentration and flow will be the same as when there is no restriction of blood flow. These studies will provide insight into the post-transcriptional regulation of muscle protein synthesis following exercise.
| Tuvdendorj, Demidmaa; Chinkes, David L; Zhang, Xiao-Jun et al. (2011) Skeletal muscle is anabolically unresponsive to an amino acid infusion in pediatric burn patients 6 months postinjury. Ann Surg 253:592-7 |
| Highstead, R Grant; Tipton, Kevin D; Creson, Daniel L et al. (2005) Incidence of associated events during the performance of invasive procedures in healthy human volunteers. J Appl Physiol 98:1202-6 |
| Durham, William J; Li, Yi-Ping; Gerken, Eric et al. (2004) Fatiguing exercise reduces DNA binding activity of NF-kappaB in skeletal muscle nuclei. J Appl Physiol 97:1740-5 |
| Borsheim, Elisabet; Aarsland, Asle; Wolfe, Robert R (2004) Effect of an amino acid, protein, and carbohydrate mixture on net muscle protein balance after resistance exercise. Int J Sport Nutr Exerc Metab 14:255-71 |
| Borsheim, Elisabet; Cree, Melanie G; Tipton, Kevin D et al. (2004) Effect of carbohydrate intake on net muscle protein synthesis during recovery from resistance exercise. J Appl Physiol 96:674-8 |
| Durham, William J; Miller, Sharon L; Yeckel, Catherine W et al. (2004) Leg glucose and protein metabolism during an acute bout of resistance exercise in humans. J Appl Physiol 97:1379-86 |
| Miller, Sharon; Chinkes, David; MacLean, David A et al. (2004) In vivo muscle amino acid transport involves two distinct processes. Am J Physiol Endocrinol Metab 287:E136-41 |
| Miller, Sharon L; Tipton, Kevin D; Chinkes, David L et al. (2003) Independent and combined effects of amino acids and glucose after resistance exercise. Med Sci Sports Exerc 35:449-55 |
| Tipton, Kevin D; Borsheim, Elisabet; Wolf, Steven E et al. (2003) Acute response of net muscle protein balance reflects 24-h balance after exercise and amino acid ingestion. Am J Physiol Endocrinol Metab 284:E76-89 |
| Borsheim, Elisabet; Tipton, Kevin D; Wolf, Steven E et al. (2002) Essential amino acids and muscle protein recovery from resistance exercise. Am J Physiol Endocrinol Metab 283:E648-57 |
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