Iron absorption and transport - An update

Iron is vital for all living organisms. However, excess iron is hazardous b ecause it produces free radical formation. Therefore, iron absorption is ca refully regulated to maintain an equilibrium between absorption and body lo ss of iron. In countries where heme is a significant part of the diet, most body iron is derived from dietary heme iron because heme binds few of the luminal intestinal iron chelators that inhibit absorption of nonheme iron. Uptake of luminal heme into enterocytes occurs as a metalloporphyrin. Intra cellularly, iron is released from heme by heme oxygenase so that iron leave s the enterocyte to enter the plasma as non-heme iron. Ferric iron is absor bed via a beta(3) integrin and mobilferrin (IMP) pathway that is not shared with other nutritional metals. Ferrous iron uptake is facilitated by DMT-1 (Nramp-2, DCT-1) in a pathway shared with manganese. Other proteins were r ecently described which are believed to play a role in iron absorption. SFT (Stimulator of Iron Transport) is postulated to facilitate both ferric and ferrous iron uptake, and Hephaestin is thought to be important in transfer of iron from enterocytes into the plasma. The iron concentration within en terocytes reflects the total body iron and either upregulates or satiates i ron-binding sites on regulatory proteins. Enterocytes of hemochromatotics a re iron-depleted similarly to the absorptive cells of iron-deficient subjec ts. Iron depletion, hemolysis, and hypoxia each can stimulate iron absorpti on. In non-intestinal cells most iron uptake occurs via either the classica l clathrin-coated pathway utilizing transferrin receptors or the poorly def ined transferrin receptor independent pathway. Non-intestinal cells possess the IMP and DMT-1 pathways though their role in the absence of iron overlo ad is unclear. This suggests that these pathways have intracellular functio ns in addition to facilitating iron uptake. Am. J. Hematol. 64:287-298, 200 0, (C) 2000 Wiley-Liss, Inc.