Binding of Trivalent Chromium to Transferrin is Sufficiently Rapid to be Physiologically Relevant

Abstract

Transferrin, the major iron transport protein in the blood, also transports trivalent chromium in vivo. Recent in vitro studies have, however, suggested that the binding of chromic ions to apotransferrin is too slow to be biologically relevant. Nevertheless, the in vitro studies have generally failed to adequately take physiological bicarbonate concentrations into account. In aqueous buffer (with ambient (bi)carbonate concentrations), the binding of chromium to transferrin is too slow to be physiologically relevant, taking days to reach equilibrium with the protein's associated conformational changes. However, in the presence of 25 mM (bi)carbonate, the concentration in human blood, chromic ions bind rapidly and tightly to transferrin. Other major potential chromium ligands in the blood plasma at physiological concentrations have little effect on the binding of chromium, consistent with transferrin being the major chromic ion transporter from the blood to tissues. The kinetics of chromium binding to human serum transferrin and conalbumin (egg white transferrin) in the presence of bicarbonate have been found to be similar. The reported binding constants for the binding of the first chromic ion to conalbumin differ by three orders of magnitude. The binding of chromic ions to conalbumin was reexamined, and the two effective chromic ion binding constants (K1 and K2) were found to be on the order of 1010 and 105, respectively.