title: Redox properties of human transferrin bound to its receptor.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Suraj
authors.initials: S
authors.lastname: Dhungana
authors.forename: Céline H
authors.initials: CH
authors.lastname: Taboy
authors.forename: Olga
authors.initials: O
authors.lastname: Zak
authors.forename: Mykol
authors.initials: M
authors.lastname: Larvie
authors.forename: Alvin L
authors.initials: AL
authors.lastname: Crumbliss
authors.forename: Philip
authors.initials: P
authors.lastname: Aisen
mesh_terms: D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D005296:Ferrous Compounds / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011990:Receptors, Transferrin / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D013816:Thermodynamics; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D005290:Ferric Compounds; D005296:Ferrous Compounds; D010446:Peptide Fragments; D011990:Receptors, Transferrin; D014168:Transferrin; C028283:diferric transferrin