Abstract
Competitive binding of Fe3+, Cr3+, and Ni2+ to transferrin (Tf) was investigated at various physiological iron to Tf concentration ratios. Loading percentages for these metal ions are based on a two Mn+ to one Tf (i.e., 100% loading) stoichiometry and were determined using a particle beam/hollow cathode–optical emission spectroscopy (PB/HC-OES) method. Serum iron concentrations typically found in normal, iron-deficient, iron-deficient from chronic disease, iron-deficient from inflammation, and iron-overload conditions were used to determine the effects of iron concentration on iron loading into Tf. The PB/HC-OES method allows the monitoring of metal ions in competition with Fe3+ for Tf binding. Iron-overload concentrations impeded the ability of chromium (15.0 μM) or nickel (10.3 μM) to load completely into Tf. Low Fe3+ uptake by Tf under iron-deficient or chronic disease iron concentrations limited Ni2+ loading into Tf. Competitive binding kinetic studies were performed with Fe3+, Cr3+, and Ni2+ to determine percentages of metal ion uptake into Tf as a function of time. The initial rates of Fe3+ loading increased in the presence of nickel or chromium, with maximal Fe3+ loading into Tf in all cases reaching approximately 24%. Addition of Cr3+ to 50% preloaded Fe3+–Tf showed that excess chromium (15.0 μM) displaced roughly 13% of Fe3+ from Tf, resulting in 7.6 ± 1.3% Cr3+ loading of Tf. The PB/HC-OES method provides the ability to monitor multiple metal ions competing for Tf binding and will help to understand metal competition for Tf binding.
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Quarles, C.D., Marcus, R.K. & Brumaghim, J.L. Competitive binding of Fe3+, Cr3+, and Ni2+ to transferrin. J Biol Inorg Chem 16, 913–921 (2011). https://doi.org/10.1007/s00775-011-0792-9
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DOI: https://doi.org/10.1007/s00775-011-0792-9