title: A mechanism for iron uptake by transferrin.
abstract: Iron uptake by transferrin from iron nitrilotriacetate (FeNAc3) in the presence of bicarbonate has been investigated in the pH range 6.5-8. Apotransferrin, in interaction with bicarbonate, extracts iron from FeNAc3, without the formation of an intermediate protein-iron-ligand mixed complex (iron-exchange-equilibrium constant, K1=1 +/- 0.05; direct second-order-rate constant, k1=8.0x10(4) +/- 0.5x10(4)M(-1)s(-1)., reverse second-order-rate constant, k-1=7.5x10(4) +/- 0.5x10(4)M(-1)s(-1). The newly formed iron-protein complex loses a single proton (proton-dissociation constant, Ka=16 +/- 1.5nM) and then undergoes a modification of its conformation followed by loss of two or three protons (first-order-rate constant, K2=2.80 +/- 0.10s-1). This includes a new modification in the conformation (first-order-rate constant, K2=6.2x10(2) +/- 0.3x10(-2)s(-1). This second modification in conformation controls the rate of iron uptake by the N-site of the protein and is followed by loss of one proton (K3a=6.80 nM). Finally, the holoprotein or the monoferric transferrin in its final equilibrated state is produced by a third modification in the conformation that occurs after approximately 3000 s. Iron uptake by the N-site does not occur when the apotransferrin interacts with bicarbonate. Nevertheless, it occurs with the monoferric transferrin, in which iron is bound to the C-site, in its final state of equilibrium by a mechanism similar to that of iron uptake by the C-site of apotransferrin. These modifications in the conformation of the protein occur after iron uptake by the C-site and may be important for the recognition of the protein by its receptor prior to iron delivery by endocytosis.
authors.affiliation: Institut de Topologie et de Dynamique des Systèmes de l'Université Denis Diderot Paris 7, France.
authors.forename: R
authors.initials: R
authors.lastname: Pakdaman
authors.forename: J M
authors.initials: JM
authors.lastname: El Hage Chahine
mesh_terms: D001059:Apoproteins / Q000378:metabolism*; D005290:Ferric Compounds / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D013053:Spectrophotometry; D014168:Transferrin / Q000378:metabolism*
chemical_list: D001059:Apoproteins; D005290:Ferric Compounds; D014168:Transferrin; C028284:apotransferrin; D007501:Iron; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate