Effect of pH and Citrate on Binding of Iron and Gallium by Transferrin in Serum

Although both Al and Fe are bound to transferrin in plasma, they are metabolized differently. Aluminum is less tightly bound to transferrin than is Fe, and might be released in circumstances in which Fe remains bound. The effect of pH ana citrate on the binding of 67Ga (a radiotracer used as an analog of Al) to transferrin in normal human serum was tested in the presence of physiological concentrations of CO2. At pH less than 6.8, Ga started to dissociate from transferrin; at pH 6, greater than 50% of the added 67Ga was present in a low-M(r) form. In contrast, almost all Fe remained bound to transferrin at pH values as low as 4.7. Citrate at concentrations as great as 100 mmol/L had no effect on binding of Fe, but the binding of 67Ga was markedly reduced at citrate greater than 1 mmol/L. Being bound to transferrin less strongly than Ga is, Al could dissociate even more readily, and loss of Al from transferrin in the kidney might explain why Al but not Fe is excreted in urine.