Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1840, Issue 6, Pages 1771-1781Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2014.01.011
Keywords
Iron-metabolism; Multi-copper oxidase; Metal-transport; Aceruloplasminemia; Protein-protein adduct
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Funding
- Lebanese National Council of Scientific Research for C. Eid PhD Grant
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Background: Dietary and recycled iron are in the Fez 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+ Methods: This study uses the techniques of chemical relaxation and spectrophotornetric detection. Results: Under 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 Cu-DS(2+). 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 (similar to 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. Conclusion: Fe3+ 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 significance: Ceruloplasmin is a go-between dietary or recycled Fe2+ and transferrin transported Fe3+. (C) 2014 Elsevier B.V. All rights reserved.
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