Next Article in Journal
Modulation of Immune Function by Polyphenols: Possible Contribution of Epigenetic Factors
Next Article in Special Issue
Intestinal Iron Homeostasis and Colon Tumorigenesis
Previous Article in Journal
Assessment of Daily Food and Nutrient Intake in Japanese Type 2 Diabetes Mellitus Patients Using Dietary Reference Intakes
Previous Article in Special Issue
Iron in Child Obesity. Relationships with Inflammation and Metabolic Risk Factors
Article Menu

Export Article

Open AccessReview

Multi-Copper Oxidases and Human Iron Metabolism

Department of Cellular and Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T1Z3, Canada
Department of Biochemistry and Molecular Biology, Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T1Z3, Canada
Author to whom correspondence should be addressed.
Nutrients 2013, 5(7), 2289-2313;
Received: 11 March 2013 / Revised: 29 May 2013 / Accepted: 6 June 2013 / Published: 27 June 2013
(This article belongs to the Special Issue Dietary Iron and Human Health)
PDF [1323 KB, uploaded 27 June 2013]


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. View Full-Text
Keywords: multi-copper oxidase; ferroxidase; ceruloplasmin; hephaestin; zyklopen multi-copper oxidase; ferroxidase; ceruloplasmin; hephaestin; zyklopen

Figure 1

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

MDPI and ACS Style

Vashchenko, G.; MacGillivray, R.T.A. Multi-Copper Oxidases and Human Iron Metabolism. Nutrients 2013, 5, 2289-2313.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Nutrients EISSN 2072-6643 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top