Iron uptake and transfer from ceruloplasmin to transferrin |
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Authors: | Chantal Eid Miryana HémadiNguyêt-Thanh Ha-Duong Jean-Michel El Hage Chahine |
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Institution: | 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 |
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Abstract: | BackgroundDietary and recycled iron are in the Fe2 + oxidation state. However, the metal is transported in serum by transferrin as Fe3 +. The multi-copper ferroxidase ceruloplasmin is suspected to be the missing link between acquired Fe2 + and transported Fe3 +.MethodsThis study uses the techniques of chemical relaxation and spectrophotometric detection.ResultsUnder anaerobic conditions, ceruloplasmin captures and oxidizes two Fe2 +. The first uptake occurs in domain 6 (< 1 ms) at the divalent iron-binding site. It is accompanied by Fe2 + oxidation by Cu2 +D6. Fe3 + is then transferred from the binding site to the holding site. Cu+D6 is then re-oxidized by a Cu2 + of the trinuclear cluster in about 200 ms. The second Fe2 + uptake and oxidation involve domain 4 and are under the kinetic control of a 200 s change in the protein conformation. With transferrin and in the formed ceruloplasmin–transferrin adduct, two Fe3 + are transferred from their holding sites to two C-lobes of two transferrins. The first transfer (~ 100 s) is followed by conformation changes (500 s) leading to the release of monoferric transferrin. The second transfer occurs in two steps in the 1000–10,000 second range.ConclusionFe3 + is transferred after Fe2 + 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.General significanceCeruloplasmin is a go-between dietary or recycled Fe2 + and transferrin transported Fe3 +. |
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Keywords: | Cp ceruloplasmin T apotransferrin Cp-T ceruloplasmin&ndash transferrin protein&ndash protein adduct CuD6 type 1 copper of domain 6 in Cp CuT type 3 copper of the trinuclear cluster of Cp CuD4 type 1 copper of domain 4 TFe2 holotransferrin TCFe TCFe-TN TFe3 + C-lobe monoferric transferrin GSH reduced glutathione |
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