title: Iron uptake and transfer from ceruloplasmin to transferrin.
abstract: BACKGROUND
  Dietary and recycled iron are in the Fe(2+) oxidation state. However, the metal is transported in serum by transferrin as Fe(3+). The multi-copper ferroxidase ceruloplasmin is suspected to be the missing link between acquired Fe(2+) and transported Fe(3+).
  
  
  METHODS
  This study uses the techniques of chemical relaxation and spectrophotometric detection.
  
  
  RESULTS
  Under anaerobic conditions, ceruloplasmin captures and oxidizes two Fe(2+). The first uptake occurs in domain 6 (<1ms) at the divalent iron-binding site. It is accompanied by Fe(2+) oxidation by Cu(2+)D6. Fe(3+) is then transferred from the binding site to the holding site. Cu(+)D6 is then re-oxidized by a Cu(2+) of the trinuclear cluster in about 200ms. The second Fe(2+) uptake and oxidation involve domain 4 and are under the kinetic control of a 200s change in the protein conformation. With transferrin and in the formed ceruloplasmin-transferrin adduct, two Fe(3+) are transferred from their holding sites to two C-lobes of two transferrins. The first transfer (~100s) is followed by conformation changes (500s) leading to the release of monoferric transferrin. The second transfer occurs in two steps in the 1000-10,000second range.
  
  
  CONCLUSIONS
  Fe(3+) is transferred after Fe(2+) uptake and oxidation by ceruloplasmin to the C-lobe of transferrin in a protein-protein adduct. This adduct is in a permanent state of equilibrium with all the metal-free or bounded ceruloplasmin and transferrin species present in the medium.
  
  
  CONCLUSIONS
  Ceruloplasmin is a go-between dietary or recycled Fe(2+) and transferrin transported Fe(3+).
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, CNRS, Interfaces, Traitements, Organisation et Dynamique des Systèmes, UMR 7086, Bâtiment Lavoisier, 15 rue Jean-Antoine de Baïf, 75205 Paris Cedex 13, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Eid
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, CNRS, Interfaces, Traitements, Organisation et Dynamique des Systèmes, UMR 7086, Bâtiment Lavoisier, 15 rue Jean-Antoine de Baïf, 75205 Paris Cedex 13, France.
authors.forename: Miryana
authors.initials: M
authors.lastname: Hémadi
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, CNRS, Interfaces, Traitements, Organisation et Dynamique des Systèmes, UMR 7086, Bâtiment Lavoisier, 15 rue Jean-Antoine de Baïf, 75205 Paris Cedex 13, France. Electronic address: thanh.haduong@univ-paris-diderot.fr.
authors.forename: Nguyêt-Thanh
authors.initials: NT
authors.lastname: Ha-Duong
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, CNRS, Interfaces, Traitements, Organisation et Dynamique des Systèmes, UMR 7086, Bâtiment Lavoisier, 15 rue Jean-Antoine de Baïf, 75205 Paris Cedex 13, France. Electronic address: chahine@univ-paris-diderot.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: El Hage Chahine
mesh_terms: D002570:Ceruloplasmin / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D010084:Oxidation-Reduction; D013053:Spectrophotometry; D014168:Transferrin / Q000737:chemistry*
chemical_list: D014168:Transferrin; D007501:Iron; D002570:Ceruloplasmin
keywords: Aceruloplasminemia; Iron-metabolism; Metal-transport; Multi-copper oxidase; Protein–protein adduct