Iron homeostasis

Andrews SC, AK Robinson, E Rodriguez-Quinones (2003) Bacterial iron homeostasis FEMS Microbiol Rev 27 215-237. 

Patients with CKD suffer from a decrease in erythropoietin production because erythropoietin is produced mainly in the kidneys.4,5 Finally, in patients with anemia of chronic disease, there is a blunted erythropoietin production as well as a diminished response to erythropoietin.9 Anemia of chronic disease also affects iron homeostasis, causing iron sequestration into storage sites and decreasing the amount available to the rest of the body.9... 

He, X, Hahn, P, Iacovelli, J, Wong, R, King, C, Bhisitkul, R, Massaro-Giordano, M, and Dunaief, JL, 2007. Iron homeostasis and toxicity in retinal degeneration. Prog Retin Eye Res 26, 649-673. 

These different systems come into operation under different conditions both environmental and in terms of growth requirements. As we will see later in this chapter, yeasts do not appear to have a mechanism for iron excretion, so that their cellular iron homeostasis, as in E. coli, relies on tight control of uptake and eventually storage. As we will see when we examine these iron uptake systems in detail, most of them require ferrous iron, rather than ferric. This implies that the first step required for iron transport is the reduction of Fe3+ to Fe2+ by membrane-bound reductases. 

Intracellular Iron Metabolism and Cellular Iron Homeostasis... 

Iron homeostasis in mammalian cells is regulated by balancing iron uptake with intracellular storage and utilization. As we will see, this is largely achieved at the level of protein synthesis (translation of mRNA into protein) rather than at the level of transcription (mRNA synthesis), as was the case in microorganisms. This is certainly not unrelated to the fact that not only do microbial cells have a much shorter division time than mammalian cells, but that one consequence of this is that the half-life of microbial mRNAs is very much shorter (typically minutes rather than the hours or often days that we find with mammals). This makes it much easier to control levels of protein expression by changing the rate of specific mRNA synthesis by the use of inducers and repressors. So how do mammalian cells... 

A Model of Iron Uptake and Regulation of Iron Homeostasis by the Enterocyte... 

One of the most notable features of this inherited defect of iron homeostasis (Chapter 9) is the ability of individuals to accumulate large amounts of iron over many years and yet show no apparent adverse effects. This may in part be due to the ability of tissues, notably the liver, to increase their iron stores gradually over a long period of time, successfully sequestrating excess iron into ferritin and, predominantly, haemosiderin. However with time the excessive deposition of iron will cause a variety of toxic effects including diabetes and arthritis which are caused by deposition of iron in these tissues. Removal of this iron by venesection can often reduce these iron-induced symptoms. 

Miller, G. (2005). The dark side of Glia. Science, 308, 778-781 Moos, T. (2002). Brain iron homeostasis. Danish Med. Bull. 49, 279-301... 

Iron chelators can also be used to selectively bind iron in areas where oxidative stress is observed, thereby preventing the iron from taking part in Fenton reactions without interfering with normal iron homeostasis. Charkoudian et al. have developed boronic acid and boronic ester masked prochelators, which do not bind metals unless exposed to hydrogen peroxide (237,238). The binding of these chelators to iron(III) prevents redox cycling. Similar studies of these systems have been performed by a separate group (239,240). 

Fe3+ (the oxidized form of Fe2+) and total iron are both found in increased concentration in the substantia nigra of patients with PD. It is now clear that exposure to iron does not pose an increased risk for the occurrence of parkinsonism, so that the increase of this metal may be related to some alteration in iron homeostasis. 

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