Inhibition of peptide chain initiation in lysates from ATP-depleted cells. II. Studies on the mechanism of the lesion and its relation to similar alterations caused by oxidized glutathione and hemin deprivation.
The impairment of peptide chain initiation in lysates from ATP-depleted rabbit reticulocytes is accompanied by a loss of their ability to form the 40 S methionyl-tRNAfMet complex with a resultant failure to promote the AUG codon-dependent combination of the complex with the 60 S ribosomal subunit. These partial initiation reactions, as well as the overall protein-synthetic activity of the defective lysates could be restored by addition of a 0.5 M KC1 ribosomal extract or normal postribosomal supernatant or a 40-70% (NH4)2-SO4 fraction derived from it. Alternatively, reactivation of the impaired lysates could be achieved by supplementation with millimolar amounts of cyclic AMP or certain purine derivatives. The same subcellular fractions, as well as cyclic AMP or purine derivatives were also capable of overcoming the inhibition caused by incubating reticulocyte lysates in the presence of oxidized glutathione or in the absence of hemin. Severe intracellular ATP deprivation resulted in accumulation of a soluble translational inhibitor in the postribosomal fraction, thus resembling the parallel phenomenon described in hemin-deprived lysates. The striking similarities between the three kinds of inhibition studied by us point to an identical site of the underlying biochemical lesion, despite the different mechanisms mediating their induction.
D000225:Adenine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D005636:Fructosephosphates / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology*; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000494:pharmacology*; D006598:Hexosediphosphates / Q000494:pharmacology; D008715:Methionine; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects*; D014176:Protein Biosynthesis / Q000187:drug effects; D012343:RNA, Transfer / Q000097:blood; D012156:Reticulocytes / Q000378:metabolism / Q000502:physiology; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014020:Tissue Extracts
D005636:Fructosephosphates; D006598:Hexosediphosphates; D014020:Tissue Extracts; D006418:Heme; D006427:Hemin; D000255:Adenosine Triphosphate; D012343:RNA, Transfer; D008715:Methionine; D000242:Cyclic AMP; D005978:Glutathione; D000225:Adenine