Effects of amino acid analogues on protein synthesis and degradation in isolated cells.
1. Naturally-occurring and synthetic analogues of phenylalanine, tyrosine, histidine, arginine, proline, tryptophan and the sulphur amino acids have beeen tested in rat reticulocytes and in the Reuber H35 hepatoma for effects on protein synthesis and protein degradation and on the heat lability of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) in the hepatoma cells. The experiments were designed to test whether the analogues could be incorporated into mammalian proteins and whether the resultant proteins would be degraded at an accelerated rate. 2. Several analogues, including thiazolylanine, triazolalanine and selenocystine both stimulated protein synthesis and produced labile protein in reticulocytes. Other analogues, such as dihydroxyphenylalanine, thioproline and pipecolic acid accelerated protein breakdown but probably indirectly via an inhibition of protein synthesis. Azetidine-2-carboxylic acid had the largest effect on protein breakdown in reticulocytes. 3. Labile protein was produced in hepatoma cells incubated in the presence of azetidine-2-carboxylic acid, canavanine, indospicine, triazolalanine, 2-, 3- and 4-fluorophenylalanine. These same analogues, together with 3,4-dehydroproline, beta-2-thienylalanine, dihydroxyphenylalanine, histidinol, 5- and 6-fluorotryptophan, selenocystine and selenomethionine produced heat-labile phosphoenolpyruvate carboxykinase. Enzyme induced in the presence of selenomethionine or indospicine showed the largest increases in heat lability, and for these analogues equimolar concentrations of methionine and arginine respectively were needed to nullify the enzyme abnormality. 4. The toxicity of the same naturally-occurring analogues has been discussed in terms of their ability to be incorporated into cell proteins.
D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000599:Amino Acids, Diamino / Q000494:pharmacology; D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D066298:In Vitro Techniques; D008113:Liver Neoplasms; D008660:Metabolism / Q000187:drug effects; D009363:Neoplasm Proteins / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D012156:Reticulocytes / Q000378:metabolism
D000596:Amino Acids; D000599:Amino Acids, Diamino; D009363:Neoplasm Proteins; D011506:Proteins; D001383:Azetidinecarboxylic Acid; D010729:Phosphoenolpyruvate Carboxykinase (GTP)