Endocrine Abstracts

Iron, an essential trace element for almost all organisms, has a structural or functional role in a number of proteins and enzymes. Total body iron amounts to ~35 and 45 mg/kg of body weight in healthy adult women and men, respectively. This iron is highly conserved and daily iron losses, normally only 0.5 to 2 mg via non-specific processes, are compensated for by absorption of an equivalent amount of iron from the diet. The precise regulation of cellular iron uptake and storage is very important if individuals are to avoid conditions of iron deficiency, as a result of a failure to absorb sufficient dietary iron, or iron overload, as a result of increased absorption of dietary iron or repeated blood transfusions, as in the case of patients with β-thalassaemia. Dietary iron and iron released from sites of haemoglobin breakdown is sequestered by transferrin, the iron-transport protein in plasma, however, it is unclear whether iron is passed directly or indirectly to transferrin. The iron saturation of transferrin is normally in the range 25–40% but in conditions of iron overload, transferrin can become fully iron-saturated and potentially toxic non-transferrin-bound iron (NTBI) can then be detected in plasma at levels of up to 10 μM.

Until about 15 years ago our understanding of the processes of dietary iron uptake, transport of iron in the blood, cellular uptake of iron and intracellular storage of iron was the result of extensive studies on the structure and function of a relatively small number of proteins, namely transferrin, ferritin, the classical transferrin receptor and iron-regulatory proteins. With the application of molecular biological and genetic techniques to the processes of mammalian iron metabolism, many novel proteins and enzymes, including HFE, hepcidin, ferroportin, DMT1, Dcytb, hephaestin, HCP1 and transferrin receptor two, have been identified and shown to play a crucial role in normal iron metabolism.