The absorption of dietary iron.
 Iron in the diet is present as either heme iron or non-heme iron. Most dietary non-heme iron is in the form of Fe³⁺, which must first be reduced to Fe²⁺ before it can be transported across the brush border membrane by DMT1. This reduction step is likely catalyzed by the brush border reductase Dcytb, although other reductases may also be involved. Once inside the enterocyte, the newly absorbed iron enters the intracellular iron pool. If the iron is not required by the body it is loaded onto the iron storage protein ferritin, a process possibly mediated by the iron chaperone PCBP1. Iron required by the body is transferred across the basolateral membrane by FPN. The export of iron also requires the ferroxidase hephaestin (HEPH), although the precise role of this protein is not known. The uptake of heme iron by enterocytes is not as well understood. HCP1 can transport heme; however, its principal role appears to be the uptake of folate and its role in heme absorption remains unclear. Once heme has been transported into the enterocytes the iron is released from the porphyrin ring by heme oxygenase 1 (HO-1), after which it enters the intracellular iron pool. Iron absorption is regulated both by systemic signals and by local iron levels. Systemic factors influencing body iron requirements are detected in the liver and affect the expression of hepcidin, which binds to FPN and induces its internalization and degradation, thereby reducing absorption. Local iron concentrations alter IRP RNA-binding activity, which in turn may affect the levels of DMT1 and FPN. These changes serve to maintain enterocyte iron levels within defined limits despite changes in dietary iron intake.
 Reprinted with permission from Anderson GJ, et al. Curr Opin Gastroenterol. 2009;25:129–135.¹⁴