The role of amino acids in the regulation of protein synthesis in perfused rat liver. I. Reduction in rates of synthesis resulting from amino acid deprivation and recovery during flow-through perfusion.

The role of perfusate amino acid concentrations in regulating rates of protein synthesis was investigated using the perfused rat liver. Livers from fed rats were perfused with a nonrecirculating medium and the incorporation of [3H]leucine into albumin and total protein was determined under conditions where the leucyl-tRNALeu and perfusate leucine specific activities were equal and constant. During perfusions of less than 1 h, rates of total protein synthesis were sensitive to the concentrations of amino acids in the perfusate. When no exogenous amino acids were provided, rates of synthesis of albumin and total protein were 40% of the maximal rates which were achieved when the medium was supplemented with 5 times the normal plasma concentrations of amino acids. However, rates of synthesis in livers perfused with amino acid-deficient medium rose with extension of the duration of perfusion to 95 min. The defect induced by amino acid deficiency did not appear to result from reductions in the charging of tRNA since no change in the quantities of amino acids bound to tRNA occurred in the amino acid-deficient perfusion. The recovery of protein synthesis with time was prevented by inhibitors of proteolysis suggesting a role for protein degradation in this phenomenon.