title: Release of iron from C-terminal monoferric transferrin to phosphate and pyrophosphate at pH 5.5 proceeds through two pathways.
abstract: Iron release fro C-terminal monoferric transferrin at pH 5.5 and 37 degrees C was studied as a function of chloride, phosphate, and pyrophosphate concentration. The rate constant for iron release depends linearly on chloride concentration, confirming that anion binding is mandatory for iron release, not only at pH 7.4 as has been previously reported, but also at pH 5.5. The extent of iron release is relatively small (< 20% for 1.0 M chloride). Concentrations of > 0.2 M phosphate are required for complete iron removal, but millimolar concentrations of pyrophosphate effect complete removal. The observed rate constants for iron release to phosphate and pyrophosphate change from one linear dependence to another less steep linear dependence on the concentration of these ligands, providing quantitative evidence that the two-pathway mechanism that we previously proposed for iron release at pH 7.4 persists at pH 5.5. According to this model, the pathway of iron release is determined by the nature of the anion occupying a kinetically significant anion binding site on the protein. The qualitative similarity of the current data with that recently reported for iron release from the transferrin-transferrin receptor complex provides strong support for the contention that the two-pathway mechanism also persists in this complex at low pH and is hence likely to be operative in vivo.
authors.affiliation: Centre for Molecular Design, Department of Chemistry, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: H M
authors.initials: HM
authors.lastname: Marques
authors.forename: T
authors.initials: T
authors.lastname: Walton
authors.forename: T J
authors.initials: TJ
authors.lastname: Egan
mesh_terms: D002712:Chlorides / Q000494:pharmacology; D011756:Diphosphates / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D008962:Models, Theoretical; D010710:Phosphates / Q000494:pharmacology*; D011485:Protein Binding; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002712:Chlorides; D011756:Diphosphates; D010710:Phosphates; D014168:Transferrin; D007501:Iron