title: The use of porphyrins as probes to examine the requirement for hemin in the maintenance of protein synthesis in reticulocyte lysates.
abstract: Hemin was compared with other porphyrins for the ability to sustain protein synthesis in reticulocyte lysates and to inhibit the phosphorylation of the alpha subunit of initiation factor 2 (eIF-2 alpha). Iron-containing porphyrins (hemin, mesohemin IX, deuterohemin IX) were found to maintain protein synthesis while iron-deficient porphyrins (protoporphyrin IX, mesoporphyrin IX) were ineffective. All of the porphyrins and metalloporphyrins tested were observed to inhibit phosphorylation of eIF-2 alpha by highly purified hemin-controlled repressor, although at different concentrations. Phosphorylation of eIF-2 alpha was examined in reticulocyte lysates. In the absence of porphyrin, phosphorylation of eIF-2 was rapid and linear for the first 7 min, during which time protein synthesis was inhibited. Both hemin and protoporphyrin IX inhibited phosphorylation of eIF-2 alpha in the lysate during this period; however, hemin sustained protein synthesis whereas protoporphyrin IX did not. Thus, the requirement for iron-containing porphyrins in the maintenance of protein synthesis is not due strictly to an inhibition of the protein kinase activity of the hemin-controlled repressor but involves an alternative, although yet undeciphered, mode of action.
mesh_terms: D000818:Animals; D015852:Eukaryotic Initiation Factor-2; D006418:Heme / Q000494:pharmacology*; D007700:Kinetics; D010448:Peptide Initiation Factors / Q000378:metabolism; D010766:Phosphorylation; D011166:Porphyrins / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D015852:Eukaryotic Initiation Factor-2; D010448:Peptide Initiation Factors; D011166:Porphyrins; D011506:Proteins; D006418:Heme