Iron is vital for almost all living organisms by participating in a wide variety of metabolic processes, including
oxygen transport,
DNA synthesis, and electron transport. However,
iron concentrations in body tissues must be tightly regulated because excessive
iron leads to tissue damage, as a result of formation of
free radicals. Disorders of
iron metabolism are among the most common diseases of humans and encompass a broad spectrum of diseases with diverse clinical manifestations, ranging from
anemia to
iron overload and, possibly, to
neurodegenerative diseases. The molecular understanding of
iron regulation in the body is critical in identifying the underlying causes for each disease and in providing proper diagnosis and treatments. Recent advances in genetics, molecular biology and biochemistry of
iron metabolism have assisted in elucidating the molecular mechanisms of
iron homeostasis. The coordinate control of
iron uptake and storage is tightly regulated by the feedback system of
iron responsive
element-containing gene products and
iron regulatory proteins that modulate the expression levels of the genes involved in
iron metabolism. Recent identification and characterization of the
hemochromatosis protein HFE, the
iron importer Nramp2, the
iron exporter ferroportin1, and the second
transferrin-binding and -
transport protein transferrin receptor 2, have demonstrated their important roles in maintaining body's
iron homeostasis. Functional studies of these gene products have expanded our knowledge at the molecular level about the pathways of
iron metabolism and have provided valuable insight into the defects of
iron metabolism disorders. In addition, a variety of animal models have implemented the identification of many genetic defects that lead to abnormal
iron homeostasis and have provided crucial clinical information about the pathophysiology of
iron disorders. In this review, we discuss the latest progress in studies of
iron metabolism and our current understanding of the molecular mechanisms of
iron absorption, transport, utilization, and storage. Finally, we will discuss the clinical presentations of
iron metabolism disorders, including secondary
iron disorders that are either associated with or the result of abnormal
iron accumulation.