Effects of amino acids on zinc transport in rat erythrocytes

1. A significant proportion of plasma zinc exists complexed with amino acids. The effect of amino acids on the accumulation of radioactive zinc by rat erythrocytes was studied in vitro, to investigate the hypothesis that zinc might be transported into cells as an amino acid-zinc complex. 2. L-Histidine (500 microM-10 mM) stimulated 65Zn uptake; 50 mM-L-histidine gave a slight inhibition of uptake. D-Histidine (500 microM-10 mM) inhibited uptake in a dose-dependent manner. A non-zinc-binding amino acid, L-alanine, did not affect 65Zn uptake. 3. The effect of L-histidine was sodium dependent and temperature dependent, but was DIDS insensitive. These properties suggest that zinc is being transported as a zinc-histidine complex, utilizing an amino acid carrier system. Uptake of zinc in the presence of L-histidine differed from the previously described ionic mechanism, and may represent a physiological route of uptake. 4. L-Histidine stimulated efflux of 65Zn from pre-loaded cells. 5. The relevance of transport of a zinc-histidine complex is discussed with reference to histidinaemia, and as a significant zinc transport system in the presence of the very low ionic zinc concentrations found in plasma.