Parallels and contrasts between iron and copper metabolism.

This paper reviews the Second International Workshop on Iron and Copper Homeostasis, held in Pucón, Chile 10-13 November, 2001. We cover the presentations and papers published (this issue) with the intent to point out parallels, contrasts and cutting edge areas rather than to say something about every paper. Iron and copper metabolism have been intertwined for nearly 150 years and the interrelationship is growing with advances in understanding the role of ceruloplasmin as one example and the probable role of hephaestin as another. The transporter DMT1 (divalent metal transporter 1) clearly plays a major part in iron uptake and trafficking. Emerging evidence suggests that it plays a lesser role in manganese, cadmium and copper transport; but it is still being evaluated there. Yet another interaction may come from the IRE/IRP (Iron Responsive Element/Iron Regulatory Protein) story where a paradigmatic role in iron homeostasis is well established, but interaction with copper is only now emerging. Parallels include the nutrient status of both metals based on their utility for redox reactions as well as their toxicity primarily via reactive oxygen species. The workshop also revealed that alternate splicing of pre-mRNAs for iron and copper related proteins and tissue specific responses are additional similarities. Regulation of gene expression and excretion offered contrasts between the two metals. The workshop also considered a series of continuing and emerging issues.