Multi-Copper Oxidases and Human Iron Metabolism
Open Access
- 27 June 2013
- Vol. 5 (7), 2289-2313
- https://doi.org/10.3390/nu5072289
Abstract
Multi-copper oxidases (MCOs) are a small group of enzymes that oxidize their substrate with the concomitant reduction of dioxygen to two water molecules. Generally, multi-copper oxidases are promiscuous with regards to their reducing substrates and are capable of performing various functions in different species. To date, three multi-copper oxidases have been detected in humans—ceruloplasmin, hephaestin and zyklopen. Each of these enzymes has a high specificity towards iron with the resulting ferroxidase activity being associated with ferroportin, the only known iron exporter protein in humans. Ferroportin exports iron as Fe2+, but transferrin, the major iron transporter protein of blood, can bind only Fe3+ effectively. Iron oxidation in enterocytes is mediated mainly by hephaestin thus allowing dietary iron to enter the bloodstream. Zyklopen is involved in iron efflux from placental trophoblasts during iron transfer from mother to fetus. Release of iron from the liver relies on ferroportin and the ferroxidase activity of ceruloplasmin which is found in blood in a soluble form. Ceruloplasmin, hephaestin and zyklopen show distinctive expression patterns and have unique mechanisms for regulating their expression. These features of human multi-copper ferroxidases can serve as a basis for the precise control of iron efflux in different tissues. In this manuscript, we review the biochemical and biological properties of the three human MCOs and discuss their potential roles in human iron homeostasis.Keywords
This publication has 147 references indexed in Scilit:
- Regulatory Effects of Cu, Zn, and Ca on Fe Absorption: The Intricate Play between Nutrient TransportersNutrients, 2013
- Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cellsBiochemical and Biophysical Research Communications, 2012
- Hereditary hemochromatosis and transferrin receptor 2Biochimica et Biophysica Acta (BBA) - General Subjects, 2012
- Friedreich's ataxia: Pathology, pathogenesis, and molecular geneticsJournal of the Neurological Sciences, 2011
- A Ferroportin Transcript that Lacks an Iron-Responsive Element Enables Duodenal and Erythroid Precursor Cells to Evade Translational RepressionCell Metabolism, 2009
- O2 Reduction to H2O by the multicopper oxidasesDalton Transactions, 2008
- Iron metabolism at the host pathogen interface: Lipocalin 2 and the pathogen-associated iroA gene clusterThe International Journal of Biochemistry & Cell Biology, 2007
- Electronic Structure of the Peroxy Intermediate and Its Correlation to the Native Intermediate in the Multicopper Oxidases: Insights into the Reductive Cleavage of the O−O BondJournal of the American Chemical Society, 2007
- Ferroxidase activity is required for the stability of cell surface ferroportin in cells expressing GPI-ceruloplasminThe EMBO Journal, 2007
- Basic and applied features of multicopper oxidases, CueO, bilirubin oxidase, and laccaseThe Chemical Record, 2007