Copper and zinc metabolism in health and disease: speciation and interactions

It has long been evident that the metabolism of trace elements cannot be considered in isolation. A wide range of nutritional and physiological factors can influence their uptake, transport and storage, with subsequent enhancement of susceptibility to deficiency or toxicity states. Interactions occur with other trace elements and these can be classified as competitive or non-competitive, direct or indirect. However, their physiological or toxicological significance is sometimes debatable, partly because they were demonstrated under extreme experimental conditions where massive doses of the antagonistic metal were administered, often by parenteral routes and to animals whose trace element status was already severely compromised. Our understanding of the mechanisms of the interactions is frequently limited and indeed in only a few cases has it been possible to describe these on a molecular basis.