Significance of conformation changes during the binding and release of chromium(III) from human serum transferrin.

Trivalent chromium has been proposed to be transported in vivo from the bloodstream to the tissues via endocytosis by transferrin (Tf), the major iron transport protein in the blood. While both Cr(III) binding and release from Tf have been proposed to be too slow to be physiologically relevant, recent kinetic studies under physiological conditions demonstrate that Cr(III) binding and release are sufficiently fast to occur during the time of the endocytosis cycle (circa 15 min). Consequently, the release of Cr(III) from human and bovine serum Tf has been examined under conditions mimicking an endosome during endocytosis. These studies have also found that Cr(III)2-Tf can exist in multiple conformations giving rise to different spectroscopic properties and different rates of Cr(III) release. Time-dependent spectroscopic studies of the binding and release of Cr(III) from human serum Tf have been used to identify three different conformations of Cr(III)2-Tf. The conformation of Cr(III)2-Tf used in most previous studies forms too slowly to be physiologically relevant and slowly releases Cr(III) in endosomal pH range. The conformation formed between 5 min to 60 min after the addition of Cr(III) to apoTf at pH 7.4 in 25 mM bicarbonate resembles the conformation of Cr(III)2-Tf in its complex with Tf receptor (TfR) and loses Cr(III) rapidly at endosomal pH, although not as fast as the Tf-TfR complex. The significance of these conformations and the potential role of Tf in detoxification of Cr(III) are described.