Iron absorption and transport-an update.
Iron is vital for all living organisms. However, excess iron is hazardous because it produces free radical formation. Therefore, iron absorption is carefully regulated to maintain an equilibrium between absorption and body loss 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 non-heme iron. Uptake of luminal heme into enterocytes occurs as a metalloporphyrin. Intracellularly, iron is released from heme by heme oxygenase so that iron leaves the enterocyte to enter the plasma as non-heme iron. Ferric iron is absorbed 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 recently 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 enterocytes reflects the total body iron and either upregulates or satiates iron-binding sites on regulatory proteins. Enterocytes of hemochromatotics are iron-depleted similarly to the absorptive cells of iron-deficient subjects. Iron depletion, hemolysis, and hypoxia each can stimulate iron absorption. In non-intestinal cells most iron uptake occurs via either the classical clathrin-coated pathway utilizing transferrin receptors or the poorly defined transferrin receptor independent pathway. Non-intestinal cells possess the IMP and DMT-1 pathways though their role in the absence of iron overload is unclear. This suggests that these pathways have intracellular functions in addition to facilitating iron uptake.
Conrad
M E
ME
University of South Alabama, Mobile, Alabama 36688, USA. mconrad@usamail.usouthal.edu
Umbreit
J N
JN
D000818:Animals; D027682:Cation Transport Proteins / Q000502:physiology; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D007501:Iron / Q000502:physiology*; D019190:Iron Overload; D008665:Metalloporphyrins / Q000378:metabolism; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D007501:Iron; D008665:Metalloporphyrins; D000099236:Solute Carrier Family 11, Member 2