Sharp · The Proceedings of the Nutrition Society 2004 · narrative review · n=?

The molecular basis of copper and iron interactions.

Cited 128 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review of mechanistic and animal data with no new clinical data.

PubMed 15831128 · doi:10.1079/pns2004386 · record verified 2026-08-29

What was done

This paper reviews the molecular mechanisms mediating the interaction between copper and iron metabolism, focusing on the roles of multi-copper ferroxidases (caeruloplasmin and hephaestin) and intestinal iron transporters (DMT1 and IREG1).

What was found

The abstract reports no numerical data. It describes that caeruloplasmin is required for iron mobilization from storage tissues, and copper deficiency impairs its ferroxidase activity, leading to anemia responsive to copper rather than iron. Hephaestin works with IREG1 to permit iron efflux from enterocytes, a process disrupted in sex-linked anemic mice bearing a truncated hephaestin mutation. Additionally, DMT1 functions as a physiologically relevant copper transporter and copper regulates both DMT1 and IREG1 expression.

Why it matters

The review clarifies the molecular pathways by which copper deficiency impairs iron homeostasis, explaining why some nutritional anemias require copper supplementation to resolve.

Limits

The abstract reports no quantitative measurements, statistical comparisons, or sample sizes. The underlying evidence relies on mechanistic reasoning and animal models such as the sla mouse rather than controlled clinical trials.

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