Iron absorption and transport

Iron is vital for living organisms because it is essential for multiple met abolic processes to include oxygen transport, DNA synthesis, and electron t ransport. However, iron must be bound to proteins to prevent tissue damage from free radical formation. Thus, its concentrations in body organs must b e regulated carefully. Intestinal absorption is the primary mechanism regul ating iron concentrations in the body. Three pathways for intestinal iron u ptake have been proposed and reported. These are the mobilferrin-integrin p athway, the divalent cation transporter 1 (DCT-1) [or natural resistance-as sociated macrophage protein (Nramp2)] pathway, and a separate pathway for u ptake of heme by absorptive cells. Each of these pathways are incompletely described. However, studies with blocking antibodies, observations in roden ts with disorders of iron metabolism, and studies in tissue culture cells s uggest that the DCT-1 pathway is dominant in embryonic cells and is involve d with cellular uptake of ferrous iron, whereas the mobilferrin-integrin pa thway facilitates absorption of dietary inorganic ferric iron. Thus, there are separate pathways for cellular uptake of ferric and ferrous inorganic i ron. Body iron can enter intestinal cells from plasma via basolateral membr anes containing the classical transferrin receptor pathway with a high affi nity for holotransferrin. This keeps the absorptive cell informed of the st ate of iron repletion of the host. intestinal mucosal cell iron seems to ex it the cell via a distinct apotransferrin receptor and a newly described pr otein named hephaestin. Unlike the absorptive surface of intestinal cells, most other cells possess transferrin receptors on their surfaces and the va st majority of iron entering these cells is transferrin associated. There s eem to be 2 distinct pathways by which transferrin iron enters nonintestina l cells. In the classical clathrin-coated pitendosome pathway, iron accompa nies transferrin into the cell to enter a vesicle, which releases the iron to the cytosol with acidification (high affinity, low capacity). Under phys iological conditions, a second transferrin associated pathway (low affinity , high capacity) exists which has been named the transferrin receptor indep endent pathway (TRIP). How the TRIP delivers iron to cells is incompletely described, in addition, tissue culture studies show that nonintestinal cell s can accept iron from soluble iron salts. This occurs via the mobilferrin- integrin and probably the DCT-1 pathways. Cellular uptake of iron from iron salts probably occurs in iron overloading disorders and may be responsible for free radical damage when the iron binding capacity of plasma is exceed ed. Radioiron entering the cell via the heme and transferrin associated pat hways can be found in isolates of mobilferrin/paraferritin and hemoglobin. This interaction probably occurs to permit NADPH dependent ferrireduction s o iron can be used for synthesis of heme proteins. Production of heme from iron delivered via these routes indicates functional specificity for the pa thways.