Release of trivalent chromium from serum transferrin is sufficiently rapid to be physiologically relevant

• Published in: Journal of inorganic biochemistry 2020-01, Vol.202, p.110901-110901, Article 110901
• Main Authors: Edwards, Kyle C., Kim, Hannah, Vincent, John B.
• Format: Article
• Language: English
• Subjects: Chromium; Chromium - isolation & purification; Chromium - metabolism; Endocytosis; Endosomes - metabolism; Humans; Ion Transport; Kinetics; Receptors, Transferrin - metabolism; Transferrin; Transferrin - metabolism; Transferrin receptor; Transport
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2019.110901

Transferrin, the major iron transport protein in the blood, apparently also transports trivalent chromium in vivo via endocytosis. Recent in vitro studies have, however, suggested that the release of chromic ions from serum transferrin is too slow to be biologically relevant. Consequently, 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 transferrin occurs rapidly from the weak binding site. While appreciably slower, the release of Cr(III) from the tighter site in the presence of biological chelating agents is potentially sufficiently fast to be physiologically relevant. When Cr(III)-loaded transferrin is added to soluble transferrin receptor, the interaction with the receptor results in Cr(III) in both the weak and tight binding sites giving rise to an EPR signal similar to that of the weak binding site; concurrently, 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 transferrin-transferrin receptor complex, thus, is easily sufficiently rapid for transferrin to serve as the physiological transporter of Cr(III) from the bloodstream to the tissues. However, detailed studies of conformational changes of transferrin associated with the binding and release of chromium along with investigations of how and at what rate Cr(III) is transported from the endosome will be required before this question of whether transferrin transport Cr(III) in vivo can be definitively resolved. The loss of transferrin-bound Cr(III) from the transferrin/soluble transfer receptor complex occurs rapidly under simulated endosomal conditions, consistent with transferrin serving as the physiological transporter of chromium from the bloodstream to the tissues. [Display omitted] •Cr(III) is released rapidly from the C-lobe binding site of transferrin at pH 4.5 and 5.5.•Release of Cr(III) from the N-lobe of transferrin is not rapid at pH 4.5 or 5.5.•Loss of Cr(III) is rapid from the transferrin-transferrin receptor complex.•Transferrin could serve as a physiological Cr(III) transporter.