Branched chain amino acids activate messenger ribonucleic acid translationregulatory proteins in human skeletal muscle, and glucocorticoids blunt this action

Branched chain amino acids (BCAA) are particularly effective anabolic agent s. Recent in vitro studies suggest that amino acids, particularly leucine, activate a signaling pathway that enhances messenger ribonucleic acid trans lation and protein synthesis. The physiological relevance of these findings to normal human physiology is uncertain. We examined the effects of BCAA o n the phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (eIF4E-BP1) and ribosomal protein S6 kinase (p70(S6K));, in skeletal muscle of seven healthy volunteers. We simultaneously examined whether BCAA affec t urinary nitrogen excretion and forearm skeletal muscle protein turnover a nd whether the catabolic action of glucocorticoids could be mediated in par t by inhibition of the action of BCAA on the protein synthetic apparatus. B CAA infusion decreased urinary nitrogen excretion (P < 0.02), whole body ph enylalanine flux (P < 0.02), plasma phenylalanine concentration (P < 0.001) , and improved forearm phenylalanine balance (P = 0.03). BCAA also increase d the phosphorylation of both eIF4E-BP1 (P < 0.02) and p70(S6K)(P < 0.03), consistent with an action to activate the protein synthetic apparatus. Dexa methasone increased plasma phenylalanine concentration (P < 0.001), prevent ed the BCAA-induced anabolic shift in forearm protein balance, and inhibite d their action on the phosphorylation of p70(S6K). We conclude that in huma n skeletal muscle BCAA act directly as nutrient signals to activate messeng er ribonucleic acid translation and potentiate protein synthesis. Glucocort icoids interfere with this action, and that may be part of the mechanism by which they promote net protein catabolism in muscle.