Redox properties of human transferrin bound to its receptor

Biochemistry. 2004 Jan 13;43(1):205-9. doi: 10.1021/bi0353631.


Virtually all organisms require iron, and iron-dependent cells of vertebrates (and some more ancient species) depend on the Fe(3+)-binding protein of the circulation, transferrin, to meet their needs. In its iron-donating cycle, transferrin is first captured by the transferrin receptor on the cell membrane, and then internalized to a proton-pumping endosome where iron is released. Iron exits the endosome to enter the cytoplasm via the ferrous iron transporter DMT1, a molecule that accepts only Fe(2+), but the reduction potential of ferric iron in free transferrin at endosomal pH (approximately 5.6) is below -500 mV, too low for reduction by physiological agents such as the reduced pyridine nucleotides with reduction potentials of -284 mV. We now show that in its complex with the transferrin receptor, which persists throughout the transferrin-to-cell cycle of iron uptake, the potential is raised by more than 200 mV. Reductive release of iron from transferrin, which binds Fe(2+) very weakly, is therefore physiologically feasible, a further indication that the transferrin receptor is more than a passive conveyor of transferrin and its iron.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Electron Spin Resonance Spectroscopy
  • Ferric Compounds / chemistry
  • Ferric Compounds / metabolism
  • Ferrous Compounds / chemistry
  • Ferrous Compounds / metabolism
  • Humans
  • Kinetics
  • Oxidation-Reduction
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Binding
  • Receptors, Transferrin / chemistry*
  • Receptors, Transferrin / metabolism*
  • Receptors, Transferrin / physiology
  • Thermodynamics
  • Transferrin / chemistry*
  • Transferrin / metabolism*


  • Ferric Compounds
  • Ferrous Compounds
  • Peptide Fragments
  • Receptors, Transferrin
  • Transferrin
  • diferric transferrin