Iron presents us with a paradox. Without it, cells simply cannot survive because
iron is an essential cofactor for many
enzymes in critical biochemical pathways. However, when
iron is present in excess, it can be highly cytotoxic due to its propensity to catalyze the formation of reactive
oxygen radicals. To cater for this dual nature, cells and organisms have developed elaborate mechanisms for regulating
iron intake and efflux. When these mechanisms are disrupted, as is the case in a number of inherited disorders of
iron metabolism, the pathological consequences can be severe. Many of these disorders are characterized by
iron overload and include relatively common diseases such as hereditary
hemochromatosis, rare abnormalities of
plasma protein synthesis (
atransferrinemia and
aceruloplasminemia), and the
neuromuscular disease Friedreich ataxia. The few described inherited
anemias in humans have yet to yield to molecular dissection, but the investigation of several rodent
anemias has proved highly rewarding. This review will provide a summary of some of these disorders and describe how their analysis has provided important new insights into
iron trafficking pathways and their regulation.