<P> Most cell types take up iron primarily through receptor - mediated endocytosis via transferrin receptor 1 (TFR1), transferrin receptor 2 (TFR2) and GAPDH . TFR1 has a 30-fold higher affinity for transferrin - bound iron than TFR2 and thus is the main player in this process . The higher order multifunctional glycolytic enzyme glyceraldehyde - 3 - phosphate dehydrogenase (GAPDH) also acts as a transferrin receptor . Transferrin - bound ferric iron is recognized by these transferrin receptors, triggering a conformational change that causes endocytosis . Iron then enters the cytoplasm from the endosome via importer DMT1 after being reduced to its ferrous state by a STEAP family reductase . </P> <P> Alternatively, iron can enter the cell directly via plasma membrane divalent cation importers such as DMT1 and ZIP14 (Zrt - Irt - like protein 14). Again, iron enters the cytoplasm in the ferrous state after being reduced in the extracellular space by a reductase such as STEAP2, STEAP3 (in erythrocytes), Dcytb (in enterocytes) and SDR2 . </P> <P> In the cytoplasm, ferrous iron is found in a soluble, chelatable state which constitutes the labile iron pool (~ 0.001 mM). In this pool, iron is thought to be bound to low - mass compounds such as peptides, carboxylates and phosphates, although some might be in a free, hydrated form (aqua ions). Alternatively, iron ions might be bound to specialized proteins known as metallochaperones . Specifically, poly - r (C) - binding proteins (PCBPs) appear to mediate transfer of free iron to ferritin (for storage) and non-heme iron enzymes (for use in catalysis). The labile iron pool is potentially toxic due to iron's ability to generate reactive oxygen species . Iron from this pool can be taken up by mitochondria via mitoferrin to synthesize Fe - S clusters and heme groups . </P> <P> Iron can be stored in ferritin as ferric iron due to the ferroxidase activity of the ferritin heavy chain . Dysfunctional ferritin may accumulate as hemosiderin, which can be problematic in cases of iron overload . The ferritin storage iron pool is much larger than the labile iron pool, ranging in concentration from 0.7 mM to 3.6 mM . </P>

Where does iron in the body come from