Suppression of Protein Turnover by Amino Acids in the Perfused Rat Liver

Abstract

Abstract Regulatory effects of amino acids on rates of protein synthesis and degradation were investigated in perfused livers from nonfasted rats. In the absence of added amino acids, the rates of incorporation of valine into and its release from protein achieved stable values from 60 to 180 min of perfusion. The infusion of a mixture of amino acids similar in composition to an ovalbumin hydrolysate, but lacking leucine, isoleucine, valine, and tyrosine, suppressed the net breakdown of protein by more than 80% as reflected by an 80% inhibition of the net release of free valine. The effect was maximal at amino acid infusion rates of 132 µmoles per hour for livers averaging 5.5 g in weight. The mixture also inhibited the release of label from livers previously labeled in vivo with l-[1-14C]valine. Since the magnitude of this effect was the same after the addition of 15 mm carrier valine, we concluded that proteolysis was the primary site of action. The response appeared to depend strongly on the presence of four amino acids, methionine, phenylalanine, proline, and tryptophan, and near-maximal responses were obtained when they were infused together at their original concentrations. Small effects were observed when these amino acids were administered singly, but full responses were not obtained even at increased rates of infusion. Rates of valine incorporation into liver protein, measured in the presence of 15 mm valine, were low at the start of perfusion, but increased spontaneously to linearity by 60 min of perfusion. Infusion of the foregoing mixture of amino acids failed to influence incorporation rates, but single additions of a complete amino acid mixture, simulating 10 times plasma levels, corrected the initial reduction and also increased incorporation rates measured after 60 min. The present findings clearly show that amino acids can suppress hepatic proteolysis in the absence of any stimulation of valine incorporation and suggest that the amino acid requirement for this suppression differs from that for stimulation of protein synthesis.