Mucosal factors molecular aspects of iron absorption and its regulation

A variety of mechanisms for the binding of non-haem iron to the mucosal membrane have been described. Both specific, saturable and receptor-mediated mechanism, and passive diffusion at higher doses may occur.

Recently discovered membrane transport proteins, regulatory proteins and associated oxidoreductases involved in iron transport through the intestinal cell are listed in Table 3.1. The proposed process is illustrated in Figure 3.3. Non-haem iron is released from food as Fe3+ and reduced by Dcytb to Fe2+. This is transported across the brush border membrane by DMT1. It is assumed that iron enters the labile pool and some may be incorporated into ferritin and lost when the cells are exfoliated. Iron destined for retention by the body is transported across the serosal membrane by ferroportin 1 before uptake by trans-ferrin as Fe3+. Hephaestin is a copper-containing ferroxidase (Table 3.1) expressed predominantly in villous cells of the small intestine. It is implicated in conversion of Fe2+ to Fe3+ in the basolateral transfer step of iron absorption, which is impaired in mice with a defective hephaestin gene. Hephaestin appears to be located intracellularly, with a perinuclear distribution, however, and its role as a ferroxidase in basolateral iron release is still unclear.

Haem iron is initially bound by haem receptors at the brush border membrane and released intracellularly by haem oxygenase

Gut lumen

Mature enterocyte

Plasma

Hepcidin

Gut lumen

Mature enterocyte

Hepcidin

Figure 3.3 Molecular pathways of iron absorption. The area enclosed in the dotted box refers to the uptake of iron from the plasma in the developing enterocyte in the intestinal crypt. Otherwise, the diagram refers to iron absorption by the villous epithelial cell. Cp, caeruloplasmin; FP1, ferroportin 1; Hp, hephaestin; Tf, transferrin; TfR, transferrin receptor. For further details see text and Table 3.1.

Iron Man Wallpaper

Decreased haem iron Decreased animal foods Ferric iron salts

Alkalis (e.g. pancreatic secretions) Insoluble iron complexes

(phytates, tannates in tea, bran)

Iron overload Decreased erythropoiesis

Inflammatory disorders (Hepcidin)

Figure 3.3 Molecular pathways of iron absorption. The area enclosed in the dotted box refers to the uptake of iron from the plasma in the developing enterocyte in the intestinal crypt. Otherwise, the diagram refers to iron absorption by the villous epithelial cell. Cp, caeruloplasmin; FP1, ferroportin 1; Hp, hephaestin; Tf, transferrin; TfR, transferrin receptor. For further details see text and Table 3.1.

before entering the labile iron pool and following a common pathway with iron of non-haem origin.

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