Chromium(III) Interaction with Transferrin and Transferrin Receptor

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Transferrin (Tf), the major iron transport protein in the blood, apparently also transports trivalent chromium via endocytosis. The release of chromium(III) from human serum transferrin has been examined under conditions mimicking an endosome during endocytosis. At pH 4.5 and 5.5, the release of Cr(III) from Tf occurs rapidly from the C-lobe binding site and slowly from the N-lobe binding site. The loss of N-lobe bound Cr(III) under these conditions is accelerated by the presence of a anionic chelating ligand. When Cr(III)-loaded transferrin is added to soluble transferrin receptor (sTfR), the loss of Cr(III) from both binding sites becomes rapid at acidic pH, more rapid than from either site in the absence of the receptor. Loss of Cr(III) from the Tf-sTfR complex is easily sufficiently rapid for Tf to serve as the physiological transporter of Cr(III) from the bloodstream to the tissues. 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 conformations of Cr(III)2-Tf. The conformation formed between 5 and 60 minutes after the addition of Cr(III) to apoTf at pH 7.4 resembles the conformation of Cr(III)2-Tf in its complex with sTfR and loses Cr(III) rapidly at endosomal pH. Loss of Cr(III) from Cr2-Tf and Cr2-Tf-sTfR in the presence of apo-chromodulin (LMWCr) results in accumulation of Cr(III) bound to LMWCr and is rapid when sTfR is present indicating the species can form under endosomal conditions and may be the next carrier in the Cr(III) transport pathway. Techniques used throughout the projects were also applied to Mn(III)2-Tf, and the first parallel mode EPR signal for Mn(III)-Tf is reported, which could prove valuable for future studies.

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