Mechanisms involved in the regulation of intestinal iron absorption.

Abstract

Iron is one of the most abundant metals in the human body. However, it is only recently that many of the molecular mechanisms involved in the absorption and metabolism of this essential trace element have been elucidated. Dietary non-haem iron is absorbed via the divalent metal transporter (DMT1) following conversion from Fe(III) to Fe(II) by both dietary reducing agents and the endogenous ferric reductase Dcytb. Efflux of iron into the plasma is achieved by the IREG1 protein working in concert with a ferrioxidase, hephaestin to allow Fe(III) to be loaded onto transferrin for onward transport in the plasma. Current consensus suggests that the regulation of intestinal iron absorption relies on signals generated in the main sites of iron storage (the liver) and utilization (the bone marrow) to indicate body iron status, which together co-ordinate intestinal uptake with body requirement. This information, conveyed by factors such as transferrin saturation and serum levels of hepcidin, is integrated by the duodenal crypt cells, which act as iron sensors and pre-programme the level of expression of the iron transport proteins relative to body iron status. Recent data suggest that mature enterocytes also possess significant plasticity and can respond rapidly (within minutes to a few hours) to local changes in dietary iron levels, fine-tuning absorption to efficiently match the body's metabolic requirements. DMT1 expression is also down-regulated by other heavy metals thought to be substrates for this transporter. This may be an adaptive mechanism to avoid toxic build up of these metals in the body.