Studies on the activation of the heme-stabilized translational inhibitor of reticulocyte lysates by oxidized glutathione and NADPH depletion.
The translational inhibition produced by addition of oxidized glutathione (GSSG) to hemin-containing reticulocyte lysates and the accompanying phosphorylation of the alpha subunit of the polypeptide chain initiation factor eIF-2 can be prevented or reversed by NADPH generators, including glucose 6-phosphate, deoxyglucose 6-phosphate, fructose 6-phosphate, NADPH itself, and also by dithiols, e.g., dithiothreitol, but not by reduced glutathione (GSH) or other monothiols, e.g., 2-mercaptoethanol. The same is true of the inhibition caused by addition of glutamate dehydrogenase, alpha-ketoglutarate, and NH4+, which may be entirely due to NADPH depletion via the reaction.
D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D015852:Eukaryotic Initiation Factor-2; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000494:pharmacology; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D019803:Glutathione Disulfide; D006418:Heme / Q000494:pharmacology*; D007656:Ketoglutaric Acids / Q000494:pharmacology; D009249:NADP / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000201:enzymology; D019892:eIF-2 Kinase
D015852:Eukaryotic Initiation Factor-2; D005958:Glucosephosphates; D007656:Ketoglutaric Acids; D010448:Peptide Initiation Factors; D011506:Proteins; D006418:Heme; D009249:NADP; D019298:Glucose-6-Phosphate; D000641:Ammonia; D005969:Glutamate Dehydrogenase; D011494:Protein Kinases; D019892:eIF-2 Kinase; D005978:Glutathione; D004229:Dithiothreitol; D019803:Glutathione Disulfide