Iron metabolism and its regulation. A review

Iron metabolism and its molecular regulation are reviewed. Ferric iron is bound to mucin in the stomach and delivered to the duodenum where it can be absorbed. Iron is transported across the apical membrane of the gut mucosa by integrin. Once within the mucosal cell, iron may be stored, utilized in protein synthesis, or exported to the serum. In the serum, iron is carried by transferrin. Diferric transferrin binds to transferrin receptor on the surface of cells and is endocytosed. In the cell, iron is bound to high and low molecular weight ligand and is thought to shuttle iron within the cell. Iron can be stored intracellularly within ferritin, or can be utilized in a number of iron containing proteins synthesized by the mitochondrion, including heme, aconitase, and cytochromes. The first chain of enzymes in the biosynthesis of heme is erythroid 5-aminolevulinate synthase (eALAS). Intracellular iron concentration regulates the synthesis of ferritin, transferrin receptor, and eALAS, thus controlling our iron metabolism. Iron regulates these proteins post-transcriptionally via iron responsive elements (IRE), which are highly conserved stem-loop structures found in messenger ribonucleic acid (mRNA), and an IRE binding protein (IRE-BP), which responds to increased intracellular iron concentrations by binding the IRE, and repressing mRNA translation or stabilizing the mRNA, depending on whether the IRE is located in the upstream or downstream untranslated regions of the mRNA. Cellular responses to iron depletion and iron over-load can be explained in terms of these regulatory mechanisms.

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