Intracellular amino acid levels as predictors of protein synthesis

Protein synthesis depends on a complete complement of precursor amino acids, specific acetylating enzymes, tRNA, and so forth. It has been related to metabolism of individual amino acids, eg, valine and leucine; however, the relation of protein synthesis to the ambient concentrations of amino acids in the intracellular and extracellular pools has not been defined. Using the viable, isolated granulocyte (leukocyte) as an in vitro cell model, protein synthesis (incorporation of 4,5-3H-leucine) has been related to simultaneous amino acid concentrations in the cell and plasma by multiple regression analysis. Fifty-five normal neonates and 30 normal adults were studied. Protein synthesis was higher in the infants than in the adults (3,527 vs 2,685 pmole/hr/mg DNA). The intracellular concentrations of most amino acids were higher than their concentrations in plasma, except for valine and citrulline, which were lower. The "aminograms" in the two pools also were very different. Forty-four percent of the variance (R2) in protein synthesis was accounted for by the intracellular concentrations of leucine, glycine, alanine, and taurine in neonates and 45% by a combination of threonine, valine, methionine, and histidine in adults. The intracellular concentrations of each of these predictor amino acids in adults were, in turn, related to different combinations of the plasma concentrations of threonine, phenylalanine, tryptophan, isoleucine, histidine, citrulline, ornithine, arginine, and glycine. Thus, it is possible to identify sets of intracellular amino acids that predict the level of protein synthesis and to delineate combinations of plasma amino acids whose levels account for a significant portion of the variance in the intracellular predictor amino acids in normal human infants and adults.