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The molecular basis of copper and iron interactions

Published online by Cambridge University Press:  07 March 2007

Paul Sharp
Paul Sharp*
Affiliation:
Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey,Guildford, GU2 7XH, UK
*
Corresponding author: Dr Paul Sharp, fax +44 1483 576978, email p.sharp@surrey.ac.uk
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Abstract

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The intimate relationship between Fe and Cu in human nutrition has been recognised for many years. The best-characterised link is provided by caeruloplasmin, a multiCu-binding protein that acts as a serum ferrioxidase and is essential for the mobilisation of Fe from storage tissues. Decreased Cu status has been shown to reduce holo-caeruloplasmin production and impair ferrioxidase activity, leading, in a number of cases, to decreased tissue Fe release and the generation of anaemia that is responsive to dietary supplementation with Cu but not Fe. Dietary Fe absorption also requires the presence of a multiCu ferrioxidase. Hephaestin, a caeruloplasmin homologue, works in concert with the IREG1 transporter to permit Fe efflux from enterocytes for loading onto transferrin. The essential role of hephaestin in this process has been recognised from studies in the sex-linked anaemic (sla) mouse, in which Fe efflux is markedly impaired as a result of a mutation in the hephaestin gene that results in a truncated and non-functional version of the protein. There is emerging evidence that a number of other components of the intestinal Fe transport pathway are also Cu sensitive. Divalent metal transporter 1 (DMT1), the Fe transporter located at the apical membrane of enterocytes, is also a physiologically-relevant Cu transporter, suggesting that these two metals may compete with each other for uptake into the duodenal enterocytes. Furthermore, expression of both DMT1 and the basolateral Fe-efflux transporter IREG1 can be regulated by Cu, suggesting that the Fe–Cu relationship may be more complex than first thought.

Keywords

CuFeAnaemiaCaeruloplasminDMT1
Type
Symposium on ‘Micronutrient interactions and public health’
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 4 , November 2004 , pp. 563 - 569
Copyright
Copyright © The Nutrition Society 2004

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