Effect of hemin and heme synthesis inhibitors on cellular protein synthesis.

Inhibitors of heme synthesis, 2,2'-bipyridyl, isonicotinic acid hydrazide (INH), and D,L-penicillamine markedly inhibited only the synthesis of hemoglobin and had no effect on the synthesis of the bulk of nonhemoglobin proteins in spleen cells of anemic mice. Exogenous hemin stimulated the synthesis of hemoglobin as well as the synthesis of the bulk of nonhemoglobin proteins. However, by further analysis of nonhemoglobin proteins it was possible to detect intermediates of hemoglobin synthesis, globin chains with highly specific radioactivity of L-[4,5-3H]leucine which were eluted together with nonhemoglobin proteins during the chromatography on CM-Sephadex C-50. Protein synthesis in Friend erythroleukemia cells of the Fw line which have the genetic defect of heme synthesis was resistant to D,L-penicillamine and Desferal; 2,2'-bipyridyl had an inhibitory effect. Hemin was without effect on protein synthesis in these neoplastic cells.