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Ferric pyrophosphate citrate: interactions with transferrin.

Raymond Pratt1, Garry J Handelman2, Thomas E Edwards3

  • 1Rockwell Medical, Wixom, MI, USA. rpratt@rockwellmed.com.

Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
|October 13, 2018
PubMed
Summary

A new iron supplement, ferric pyrophosphate citrate (FPC), directly transfers iron to transferrin. This novel parenteral iron formulation avoids the release of toxic free iron, unlike conventional intravenous iron supplements.

Keywords:
Crystal structureFerric pyrophosphate citrateIronKineticsTransferrin

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Area of Science:

  • Biochemistry
  • Nanotechnology
  • Pharmacology

Background:

  • Intravenous iron supplements typically use iron-carbohydrate nanoparticles.
  • These nanoparticles release iron via the reticuloendothelial system, risking toxic free iron exposure.
  • Conventional formulations can lead to cellular damage due to iron's redox activity.

Purpose of the Study:

  • To investigate a novel parenteral iron formulation, ferric pyrophosphate citrate (FPC).
  • To determine if FPC can directly transfer iron to apo-transferrin.
  • To assess the safety and mechanism of iron delivery by FPC compared to conventional iron supplements.

Main Methods:

  • Characterization of FPC's unique iron-complex structure.
  • Kinetic analysis of iron transfer from FPC to apo-transferrin.
  • Crystal structure determination of transferrin bound to FPC.

Main Results:

  • FPC directly and rapidly donates iron to apo-transferrin.
  • Iron transfer occurs efficiently to both binding sites within transferrin.
  • The FPC structure encapsulates iron, preventing exposure of redox-active free iron.

Conclusions:

  • Ferric pyrophosphate citrate (FPC) offers a safer alternative for parenteral iron therapy.
  • FPC's direct iron transfer mechanism mitigates the risks associated with free iron toxicity.
  • This novel formulation enhances iron delivery to transferrin without cellular damage.