Difference between the two iron-binding sites of transferrin

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 sites 1 , the sites behave in a non-equivalent manner. Since the initial report by Fletcher and Huehns 2 , 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 Gibson 9 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 Perkins 11 reported that bicarbonate displaces only one oxalate anion from the (oxalate) 2 –Fe 2 –transferrin complex. We now report experiments on the p H-dependent dissociation of diferric transferrin which indicate that there is a difference in the iron-binding properties of each site.