Ironing out disease: Inherited disorders of iron homeostasis

Iron presents us with a paradox, Without it, cells simply cannot survive be cause iron is an essential cofactor for many enzymes in critical biochemica l pathways, However, when iron is present in excess, it can be highly cytot oxic due to its propensity to catalyze the formation of reactive oxygen rad icals, To cater for this dual nature, cells and organisms have developed el aborate mechanisms for regulating iron intake and efflux, When these mechan isms are disrupted, as is the case in a number of inherited disorders of ir on metabolism, the pathological consequences can be severe. Many of these d isorders are characterized by iron overload and include relatively common d iseases such as hereditary hemochromatosis, rare abnormalities of plasma pr otein synthesis (atransferrinemia and aceruloplasminemia), and the neuromus cular disease Friedreich ataxia. The few described inherited anemias in hum ans have yet to yield to molecular dissection, but the investigation of sev eral rodent anemias has proved highly rewarding. This review will provide a summary of some of these disorders and describe how their analysis has pro vided important new insights into iron trafficking pathways and their regul ation.