The influence of inorganic anions on the formation and stability of Fe3+-transferrin-anion complexes.
Harris (Biochemistry 24 (1985) 7412) reports that inorganic anions bind to human apotransferrin in such a way as to perturb the ultraviolet spectrum. The locus of binding is thought to involve the specific metal/anion-binding sites since no perturbation is observed with Fe3+-transferrin-CO3(2-). Paradoxically, we were unable to demonstrate the formation of Fe3+-transferrin-inorganic anion complexes despite the presence of high concentrations of SO4(2-), H2PO4-, Cl-, ClO4- or NO3-. Similar results were found for human lactoferrin. Electron paramagnetic resonance spectroscopy and visible spectrophotometry were used to monitor the results. An attempt to form the H2PO4- complex by displacement of glycine from Fe3+-transferrin-glycine resulted only in the disruption of the ternary complex. A series of inorganic anions varied in their ability to release iron from Fe3+-transferrin-CO3(2-) at pH 5.5, the approximate pH of endosomes where iron release takes place within cells. The order of effectiveness was H2P2O7(2-) much greater than H2PO4- greater than SO4(2-) greater than NO3- greater than Cl- greater than ClO4-. The rate of iron removal from Fe3+-transferrin-CO3(2-) at pH 5.5 by a 4-fold excess of pyrophosphate was greatly enhanced by physiological NaCl concentration. Iron removal was complete within 10 min, the approximate time for iron release from Fe3+-transferrin-CO3(2-) in developing erythroid cells. Thus, inorganic anions may have a significant effect on the release of iron under physiological conditions despite the fact that such inorganic anions cannot act as synergistic anions. The results are discussed in relation to a special role for the carboxylate group in allowing ternary complex formation.
Foley
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Department of Biochemistry and Biophysics, Texas A & M University, College Station 77843.
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D000838:Anions / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism; D002704:Chlorates / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007781:Lactoferrin / Q000378:metabolism; D009566:Nitrates / Q000494:pharmacology; D010756:Phosphoric Acids / Q000494:pharmacology; D013053:Spectrophotometry; D013431:Sulfates / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism*
D000838:Anions; D001639:Bicarbonates; D002704:Chlorates; D002712:Chlorides; D005290:Ferric Compounds; D009566:Nitrates; D010756:Phosphoric Acids; D013431:Sulfates; D014168:Transferrin; D007781:Lactoferrin; D005998:Glycine