Influence of amino acid availability on protein turnover in perfused skeletal muscle

Abstract

The effects of amino acids on protein turnover in skeletal muscle were determined in the perfused rat hemicorpus preparation. Perfusion of preparations from fasted young rats (81±2 g) with medium containing either a complete mixture of amino acids at five times (5×) their normal plasma levels, a mixture of leucine, isoleucine, and valine at 5× or 10× levels, or leucine alone (10×) resulted in a 25–50% increase in muscle protein synthesis and a 30% decrease in protein degradation compared to fasted controls perfused in the absence of exogenously added amino acids. When the branched-chain amino acids were omitted from the complete mixture, the remaining amino acids (5×) had no effect on protein turnover. The complete mixture at 1× levels was also ineffective. Comparison of the effects of amino acids with those of glucose and palmitate indicated that amino acids were not acting by providing substrates for energy metabolism. The stimulatory effect of amino acids on protein synthesis was associated with a facilitated rate of peptide-chain initiation as evidenced by a relative decrease in the level of ribosomal subunits. This response was not as great as that produced by insulin, and the amino acids did not augment the effect of insulin. Although protein synthesis in preparations from fed young rats (130±3 g) was stimulated by the addition of a mixture of the branched-chain amino acids (5×) to about the same extent as that observed in the fasted young rats, protein degradation was not affected. Furthermore, neither synthesis nor degradation were affected in preparations from fasted older rats (203±9 g) suggesting that the age and or nitritional state of the animal may influence the response of skeletal muscle to altered amino acid levels.