The role of translational inhibitor in ethionine-induced inhibition of protein synthesis.
The soluble fraction from rat liver contains an inhibitor of protein chain initiation when tested in a cell-free protein-synthesizing system derived from rabbit reticulocytes. The administration of ethionine to rats increased the inhibitory activity in the liver. This liver inhibitor displayed properties similar to those of hemin-controlled inhibitor found in rabbit reticulocytes: (i) the liver inhibitor inhibited protein chain initiation in rabbit reticulocyte lysate with characteristic biphasic kinetics; (ii) the liver inhibitor disaggregated the reticulocyte polysomes with a concomitant increase in 80 S ribosomes; (iii) the inhibition was prevented or reversed by eIF-2. The activation of the liver inhibitor by ethionine was rapidly and completely counteracted by the subsequent administration of methionine and adenine to rats. The mechanism of inhibition of protein synthesis by ethionine was discussed in the light of these findings.
D000818:Animals; D005001:Ethionine / Q000494:pharmacology*; D015852:Eukaryotic Initiation Factor-2; D005260:Female; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D015852:Eukaryotic Initiation Factor-2; D010448:Peptide Initiation Factors; D011506:Proteins; D005001:Ethionine