Difference between the two iron-binding sites of transferrin

Abstract

THE protein transferrin has a central role in iron metabolism, transporting the metal between absorption, utilisation, excretion, reclamation and storage areas. Although two ferric ions are bound at apparently equivalent iron-binding sites¹, the sites behave in a non-equivalent manner. Since the initial report by Fletcher and Huehns², there have been observations in vivo and in vitro of the unique biological specificity for transferrin iron bound at each site^3–8. Physicochemical evidence for any difference between iron binding at each site is sparse. Price and Gibson⁹ observed electron paramagnetic resonance (EPR) spectral differences arising from each site under the influence of the chaotropic agent perchlorate. Aisen et al.¹⁰ observed EPR differences between sites for the chromium complex and Young and Perkins¹¹ reported that bicarbonate displaces only one oxalate anion from the (oxalate)₂–Fe₂–transferrin complex. We now report experiments on the pH-dependent dissociation of diferric transferrin which indicate that there is a difference in the iron-binding properties of each site.