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Multi-Copper Oxidases and Human Iron Metabolism

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 diff...

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Autores principales: Vashchenko, Ganna, MacGillivray, Ross T. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738974/
https://www.ncbi.nlm.nih.gov/pubmed/23807651
http://dx.doi.org/10.3390/nu5072289
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author Vashchenko, Ganna
MacGillivray, Ross T. A.
author_facet Vashchenko, Ganna
MacGillivray, Ross T. A.
author_sort Vashchenko, Ganna
collection PubMed
description 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 Fe(2+), but transferrin, the major iron transporter protein of blood, can bind only Fe(3+) 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.
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spelling pubmed-37389742013-08-09 Multi-Copper Oxidases and Human Iron Metabolism Vashchenko, Ganna MacGillivray, Ross T. A. Nutrients Review 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 Fe(2+), but transferrin, the major iron transporter protein of blood, can bind only Fe(3+) 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. MDPI 2013-06-27 /pmc/articles/PMC3738974/ /pubmed/23807651 http://dx.doi.org/10.3390/nu5072289 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Vashchenko, Ganna
MacGillivray, Ross T. A.
Multi-Copper Oxidases and Human Iron Metabolism
title Multi-Copper Oxidases and Human Iron Metabolism
title_full Multi-Copper Oxidases and Human Iron Metabolism
title_fullStr Multi-Copper Oxidases and Human Iron Metabolism
title_full_unstemmed Multi-Copper Oxidases and Human Iron Metabolism
title_short Multi-Copper Oxidases and Human Iron Metabolism
title_sort multi-copper oxidases and human iron metabolism
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738974/
https://www.ncbi.nlm.nih.gov/pubmed/23807651
http://dx.doi.org/10.3390/nu5072289
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