Toxicity of copper, cobalt, and nickel salts is dependent on histidine metabolism in the yeast Saccharomyces cerevisiae

The pH-dependent inhibition of 22 metal salts was systematically examined for the yeast Saccharomyces cerevisiae. It was observed that the inhibition of growth by Cu, Co or Ni salts is substantially increased by histidine auxotrophy and by increasing the pH of the medium. Deletion of the high-affinity histidine permease Hip1p in His- strains caused greater sensitivity to Cu, Co and Ni and the requirement of a higher level of histidine to reverse the inhibition. It was concluded that intracellular histidine reduces the pH-dependent toxicity of Cu, Co and Ni.