Reversible Inhibition by Histidinol of Protein Synthesis in Human Cells at the Activation of Histidine

Abstract l-Histidinol has been found to be a potent, reversible inhibitor of protein synthesis in cultured human cells. When the culture medium contains 0.005 mm histidine, protein synthesis is inhibited 50% by 0.1 mm histidinol. Histidinol does not significantly affect the transport of histidine into cells or the amount of histidine accumulated in the free amino acid pool. Histidinol probably inhibits protein synthesis by decreasing the activation of histidine since it competitively inhibits the pyrophosphate-ATP exchange reaction promoted by crude histidyl-tRNA synthetase in the presence of histidine, with an apparent Ki of 4 x 10-7 m. Histidinol alone will not support the exchange reaction. The inhibition by histidinol of the over-all histidine charging reaction with tRNA is also competitive. The apparent Ki of histidinol for the charging reaction, under different reaction conditions than the exchange reaction, is 3 x 10-6 m. Histidinol appears to be a useful inhibitor for studying the regulation of macromolecule synthesis in cultured human cells.