title: Titanium preferential binding sites in human serum transferrin at physiological concentrations.
abstract: Serum transferrin (Tf) is an iron binding glycoprotein that plays a central role in the metabolism of this essential metal but it also binds other metal ions. Four main transferrin forms containing different iron binding states can be distinguished in human serum samples: monoferric (C-site or N-site), holotransferrin (with two Fe atoms) and apotransferrin (with no metal). Recently, it has been reported that Tf binds also Ti even more tightly than does Fe, in artificially Ti(iv) spiked solutions. However, very limited work has been done on the Ti binding to Tf at physiological concentrations in patients carrying intramedullary Ti nails. Here we report the chemical association of Ti to Tf "in vivo" under different chromatographic conditions by elemental mass spectrometry using double focusing inductively coupled plasma (DF-ICP-MS) as detector. For the separation of the Ti/Fe-Tf forms different gradient conditions have been explored. The observed results reveal that human serum Ti (from patients carrying intramedullary Ti nails) is uniquely associated to the N-lobe of Tf. The investigation of the influence of sialic acid in the carbohydrate chain of human serum Tf, studied by incubating the protein with neuraminidase (sialidase) to obtain the monosialilated species, revealed that the binding affinity of Ti was similar for monosialo-Tf and for native-Tf and occurs in the N-lobe. These results suggest that the species Fe(C)Ti(N)-TF might provide a route for Ti entry into cells via the transferrin receptors after the release of the metal from its implants.
authors: Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain.
authors: Yoana
authors: Y
authors: Nuevo-Ordoñez
authors: M
authors: M
authors: Montes-Bayón
authors: E
authors: E
authors: Blanco González
authors: A
authors: A
authors: Sanz-Medel
mesh_terms: D001665:Binding Sites; D002845:Chromatography; D006801:Humans; D007501:Iron / Q000302:isolation & purification; D011485:Protein Binding; D012794:Sialic Acids / Q000032:analysis / Q000302:isolation & purification; D014025:Titanium / Q000302:isolation & purification / Q000378:metabolism*; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D012794:Sialic Acids; D014168:Transferrin; D014025:Titanium; D007501:Iron