Abstract
Elemental iron, like molecular oxygen, is a highly toxic substance that is nevertheless essential for life. Therefore, like oxygen, complex biochemical systems have evolved for its safe delivery, transport, and utilization. Iron absorption in the human gut is a highly regulated process that depends in part on total body iron stores (FLanagan 1990; MCLAren et al. 1981). Loss of regulation, or stimulated transport in anemic states, contributes to iron overload and in some cases a need for chelation. Very few details of the processes involved in absorption are known. Safe transport of newly absorbed iron through the circulation is achieved by binding to the transport protein, transferrin. Transferrin has two iron-binding sites with association constants (log K) of 22.1 and 22.7 (MArtin et al. 1987), so iron is bound tightly in a non-redox-active form and is effectively nonexchangeable with other ligands normally present in plasma. Human transferrin is typically about one-third saturated with iron (MCLAren et al. 1981) so there is a large reserve capacity to accommodate additional iron. Controlled delivery of iron to tissues such as the liver is generally achieved by receptor-mediated endocytosis of a transferrin — transferrin-receptor complex, which dissociates in an acidified endosomal compartment (AIsen 1992; THeil and AIsen 1987), ultimately releasing iron for incorporation into its storage form, ferritin. The completed ferritin molecule comprises 24 protein subunits that surround an iron core with a basic ferric oxohydroxide structure as well as phosphate ligands. Up to 4500 atoms of iron can be accommodated in this core, which is coated by the peptides (THeil 1987). Utilization of ferritin iron, for example for the synthesis of cytochromes and other hemoproteins, may require reductive enzymatic release of iron from the relatively inert and sequestered core (THeil 1987).
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Templeton, D.M. (1995). Therapeutic Use of Chelating Agents in Iron Overload. In: Goyer, R.A., Cherian, M.G. (eds) Toxicology of Metals. Handbook of Experimental Pharmacology, vol 115. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79162-8_14
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