Effects of amino acids and amino acid analogues on lysosomal protein degradation in isolated rat hepatocytes.

An amino acid mixture, specially designed to improve the protein balance in isolated hepatocytes, inhibited lysosomal (propylamine-sensitive) degradation of endogenous proteins by 80-90%. The amino acids had no effect on the degradation of the endocytosed protein asialofetuin, the conclusion being that amino acids are involved in the regulation of autophagy. Furthermore, the effect of two amino acids was tested individually, at high concentrations, in an electron microscopic analysis. Leucine caused a 79% decrease in the early forms of autophagic vacuoles, while asparagine had no effect. Leucine appears to be important in the regulation of the bulk autophagy observable in the electron microscope but this type of autophagy possibly contributes only about one-half of the total amount of protein degraded in lysosomes, since leucine only inhibits some 30% of the lysosomal protein degradation. Certain branched-chain amino acids related to leucine inhibited lysosomal protein degradation to the same extent as did leucine.