Mechanism of action of a microsomal inhibitor of protein synthesis potentiated by oxidized glutathione.
Extracts of microsomal fractions cause an inhibition of protein synthesis that is most pronounced in the presence of 0.1mm-GSSG and 0.01mm-GTP, and is abolished by thiol or 0.4mm-GTP (Scornik et al., 1967). Fractionation of microsomal extracts showed that this inhibition of protein synthesis was caused by an enzyme, nucleoside diphosphate phosphohydrolase. Direct inhibition of protein synthesis on detergent-treated polyribosomes by 0.1mm-GSSG was observed under conditions of GTP limitation induced by omission of a GTP-regenerating system, or addition of a nucleoside triphosphate diphosphohydrolase. Thus GSSG potentiated the inhibition of protein synthesis caused by an enzyme that promoted removal of GTP. The inhibition was abolished by adding 4mm-2-mercaptoethanol or 0.4mm-GTP. Nucleoside diphosphate phosphohydrolase was thought also to act by promoting removal of GTP, thus causing an inhibition of protein synthesis that was potentiated by GSSG.
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000818:Animals; D002250:Carbon Radioisotopes; D002848:Chromatography, DEAE-Cellulose; D005260:Female; D005978:Glutathione / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D008623:Mercaptoethanol / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects*; D009711:Nucleotides; D010744:Phosphoric Monoester Hydrolases / Q000494:pharmacology; D011132:Polyribosomes; D014176:Protein Biosynthesis; D051381:Rats; D013501:Surface-Active Agents
D002250:Carbon Radioisotopes; D009711:Nucleotides; D013501:Surface-Active Agents; D008623:Mercaptoethanol; D000244:Adenosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D010744:Phosphoric Monoester Hydrolases; D005978:Glutathione; D007930:Leucine