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

J Inorg Biochem. 2025 Feb:263:112773. doi: 10.1016/j.jinorgbio.2024.112773. Epub 2024 Nov 17.

Abstract

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.

Keywords: Ferric pyrophosphate citrate; Metalloforms; Micellar electrokinetic chromatography; Pyrophosphate; Synergistic anion; Transferrin.

MeSH terms

  • Citric Acid / chemistry
  • Diphosphates* / chemistry
  • Electrophoresis, Capillary
  • Ferric Compounds / chemistry
  • Humans
  • Iron Chelating Agents / chemistry
  • Iron* / chemistry
  • Iron* / metabolism
  • Transferrin* / chemistry
  • Transferrin* / metabolism

Substances

  • Transferrin
  • Diphosphates
  • Iron
  • Iron Chelating Agents
  • Citric Acid
  • diphosphoric acid
  • Ferric Compounds