title: Effects of amino acid analogues on protein degradation in isolated rat hepatocytes.
abstract: Analogues and derivatives of six of the amino acids which most effectively inhibit protein degradation in isolated rat hepatocytes (leucine, asparagine, glutamine, histidine, phenylalanine and tryptophan) were investigated to see if they could antagonize or mimic the effect of the parent compound. No antagonists were found. Amino alcohols and amino acid amides tended to inhibit protein degradation strongly, apparently by direct lysosomotropic effect as indicated by their ability to cause lysosomal vacuolation. Amino acid alkyl esters and dipeptides inhibited degradation to approximately the same extent as did their parent amino acids, possibly by being converted to free amino acids intracellularly. Of several leucine analogues tested, four (L-norleucine, L-norvaline, D-norleucine and L-allo-isoleucine) were found to be as effective as leucine in inhibiting protein degradation. None of the analogues had any effect on protein synthesis. Since leucine appears to play a unique role as a regulator of bulk autophagy in hepatocytes, the availability of active leucine agonists may help to elucidate the biochemical mechanisms for control of this important process.
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives; D001343:Autophagy; D005973:Glutamine / Q000031:analogs & derivatives; D006639:Histidine / Q000031:analogs & derivatives; D007930:Leucine / Q000031:analogs & derivatives; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010649:Phenylalanine / Q000031:analogs & derivatives; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000031:analogs & derivatives
chemical_list: D000596:Amino Acids; D011506:Proteins; D005973:Glutamine; D010649:Phenylalanine; D006639:Histidine; D001216:Asparagine; D014364:Tryptophan; D007930:Leucine