Physiological iron chelators pyrophosphate and citrate have different effects on the proportions of monoferric transferrin metalloforms

Human serum transferrin can bind up to two iron atoms, one in each of its two domains which are known as the N-lobe and the C-lobe. Ferric pyrophosphate and ferric citrate have been shown to direct loading into the C-lobe and N-lobe, respectively. We report that the iron supplement ferric pyrophosph...

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Veröffentlicht in:Journal of inorganic biochemistry 2025-02, Vol.263, p.112773, Article 112773
Hauptverfasser: Harris, Shelby T., Gardner, Jordan, Davis, Alexia, Steed, Julia, Christiansen, Steven, Ryberg, Stewart, Ludlow, Weston, Pendleton, Mitchell, Grimshaw, Blake, Watt, Richard K.
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Sprache:eng
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Zusammenfassung:Human serum transferrin can bind up to two iron atoms, one in each of its two domains which are known as the N-lobe and the C-lobe. Ferric pyrophosphate and ferric citrate have been shown to direct loading into the C-lobe and N-lobe, respectively. We report that the iron supplement ferric pyrophosphate citrate directs iron to the C-lobe. We also show that pyrophosphate directs iron to the C-lobe as a free anion even at the concentrations found in human plasma. This indicates that pyrophosphate may play a physiological role in transferrin iron loading and body iron homeostasis. We also present a validation of an existing micellar capillary electrophoresis technique for separating the four transferrin metalloforms, which has potential to be adapted for use in a clinical setting. A previously developed micellar electrokinetic chromatography (MEKC) technique was validated against urea polyacrylamide gel electrophoresis for separation of transferrin metalloforms. This MEKC technique was then used to analyze the lobe-specificity of iron supplement ferric pyrophosphate citrate, and to elucidate a potential physiological effect of serum pyrophosphate in transferrin iron loading. [Display omitted] •MEKC validated against urea gels for separation of transferrin metalloforms.•Found that FPC preferentially loads the C-terminal domain of transferrin.•PPi found to increase relative proportion of FeC-Tf at physiological concentrations.
ISSN:0162-0134
1873-3344
1873-3344
DOI:10.1016/j.jinorgbio.2024.112773