Regulation of human skeletal muscle protein metabolism: Effect of exercise, nutrition and physical training

The present thesis utilized acute exercise, physical training and nutritional interventions to probe the regulation of human skeletal muscle protein and amino acid metabolism. Young active men and women were studied before, during and in recovery from prolonged moderate-intensity exercise. In two investigations, subjects were studied before and after 6-7 wk of training to examine changes in the regulation of the free amino acid pool and the activity state of branched-chain oxoacid dehydrogenase (BCOAD), the rate-determining enzyme for amino acid oxidation in muscle. The other two studies involved manipulating carbohydrate (CHO) and protein availability to determine the effect on skeletal muscle and whole-body protein turnover using stable isotope tracer techniques.; Training increased the content of glutamate and taurine, the two most abundant amino acids in muscle that play key roles in inter-organ physiology. Training also reduced the exercise-induced changes in the muscle contents of glutamate and alanine, consistent with an attenuated expansion of the tricarboxylic acid cycle intermediate pool. BCOAD activity was reduced after training and this was associated with an increased muscle content of BCOAD kinase, the enzyme responsible for BCOAD inactivation by phosphorylation.; Co-ingestion of protein with a high rate of CHO during recovery from prolonged exercise did not alter glycogen synthesis, but increased mixed skeletal muscle fractional synthetic rate compared to CHO alone. In contrast, restricting CHO availability increased net skeletal muscle protein catabolism during and following exercise, due to both a reduced protein synthesis rate and increased rate of protein breakdown. Restricting CHO availability also increased net whole-body protein breakdown and enhanced skeletal muscle glucose uptake rate.; Finally, novel insights revealed in the present thesis highlight differences in models used to study the regulation of skeletal muscle protein metabolism, as the human data sometimes differed from previous findings shown in rats.