Ferritin and Hemosiderin

It is well known that iron in living systems is stored in ferritin and hemosiderin. A number of reviews have been published in the recent years, summarizing the present knowledge about ferritin and hemosiderin [MO] and the mineralization process leading to the formation of the iron core [III]. 

Bauminger and Harrison reviewed studies of the process of iron core formation in human and horse spleen ferritins using Mossbauer spectroscopy. It was demonstrated that iron deposition within ferrihydrite core in human and horse spleen ferritin started with Fe(ll) oxidation. This process was associated with ferroxidase center of H-chains. Further, an Fe(lll) compound and Fe(lll) jL-oxo-bridged dimers in ferroxidase centers of H-chains were found, which were intermediate compounds in the process of iron oxyhydroxide core formation in horse spleen ferritin. The steps leading to ferrihydrite core formation in human L- and H-ferritins were also identified and transfer between ferritin molecules was established [M2]. 

Mossbauer spectra of ferritin and hemosiderin from the heart of patients with -thalassemia/hemoglobin E were obtained in Ref. 120. It was suggested that the iron cores had structures based on the mineral ferrihydrite and were superparamagnetic with a mean blocking temperature of 34K. The hemosiderin particles had a very poor crystalline structure. 

Papaefthymiou outlined possible directions of future Mossbauer studies in the most recent review [130]. Among them there is a study on magnetic properties that up to now reported about differences in ferritin particles behavior. It is not clear yet whether iron storage conditions and the iron core structure influenced the magnetic properties of ferritin. 

Mossbauer spectra of human liver ferritin (a), Imferon (b), Maltofer (c), and Ferrum Lek(d) measured atT = 295 K with a high velocity resolution and presented in 2048 channels (a, b, d) and in 4096 channels (c), indicated components are the results of the best fit and relationship between the spectral hyperfine parameters for Imferon ( ), Maltofer (A), Ferrum Lek ( ), and human liver ferritin (A) obtained using one quadrupole doublet fit (e) [129], 

Under normal conditions ferritin accounts for more than half of the iron in storage. As iron loading is increased the balance alters hemosiderin increases relative to ferritin, and, in extreme cases, forms discrete deposits that may cause tissue damage. The majority of the iron that is contained in ferritin is found in the liver and spleen. Iron is also deposited in the ferritin of erythroid cells during the early stages of erythroid differentiation. Tissue 

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This loss is compensated by the alimentation. 70 % of the body iron is contained in hemoglobin. Transferrin ensures the transport of iron, while ferritin and hemosiderin are used for the storage of iron in a non-toxic form ferritin is indeed able to transform the highly toxic Fe(II) in to the less toxic Fe(III). 

The problems to be solved are listed hereafter the first problem is the lack of data concerning the exact proportions of low-molecular weight iron complex, ferritin-bound iron and hemosiderin-bound iron (54). However, transverse NMRD profiles of iron-loaded tissues indicate that the transverse relaxation is essentially caused by ferritin, because of the linearity between I/T2 and Bq, which is a fingerprint of ferritin-induced relaxation. The relaxation properties of hemosiderin are less understood. If the proportion of ferritin and hemosiderin is not the same in all of the studied tissues, the correlation between the relaxation properties and the total iron concentration could be affected. 

As the human body is able to store many minerals, deviations from the daily ration are balanced out over a given period of time. Minerals stored in the body include water, which is distributed throughout the whole body calcium, stored in the form of apatite in the bones (see p. 340) iodine, stored as thyroglobulin in the thyroid and iron, stored in the form of ferritin and hemosiderin in the bone marrow, spleen, and liver (see p. 286). The storage site for many trace elements is the liver. In many cases, the metabolism of minerals is regulated by hormones—for example, the uptake and excretion of H2O, Na, ... 

The body iron is distributed mainly in two forms, one as haem in haemoglobin and cytochrome oxidase enzyme and other as iron bound to protein as storage compounds ferritin and hemosiderin, and as transport iron bound to transferrin. The total body iron in human adult is approximately 3.5 g out... 

In an adult human some 65% of the total iron is found in hemoglobin and myoglobin, and the bulk of the remainder is found in the storage proteins ferritin and hemosiderin. A small amount is utilized in iron enzymes at any one time. An account will be given of ferritin and the transport protein transferrin, prior to a general discussion of iron transport and storage. 

The majority of body iron is not chelatable (iron from cytochromes and hemoglobin). There are two major pools of chelatable iron by DFO (19). The first is that delivered from the breakdown of red cells by macrophages. DFO competes with transferrin for iron released from macrophages. DFO will also compete with other plasma proteins for this iron, when transferrin becomes saturated in iron overload. The quantity of chelatable iron from this turnover is 20mg/day in healthy individuals and iron chelated from this pool is excreted in the urine (19). The second major pool of iron available to DFO is derived from the breakdown of ferritin and hemosiderin. The ferritin is catabolized every 72 hours in hepatocytes, predominantly within lysosomes (I). DFO can chelate iron that remains within lysosomes shortly after ferritin catabolism or once this iron reaches a dynamic, transiently chelatable, cytosolic low-molecular-weight iron pool (20). Cellular iron status, the rate of uptake of exogenous iron, and the rate of ferritin catabolism are influent on the level of a labile iron pool (21). Excess ferritin and... 

Approximately 20 mg of iron is required daily for erythropoiesis. The iron requirements are supplied by recycled iron and from residual body iron stores. One major store is in hepato-cytes where 0.5-1 g of iron is bound to specialized proteins such as ferritin and hemosiderin. Ferritin is a large, 440-kd cellular storage protein for iron. Measurement of plasma ferritin is seen as a reflection of the cellular ferritin stores, which in turn reflects cellular iron stores. Body stores of iron are maintained by recycling Senescent erythrocytes are ingested by macrophages, and their iron is taken up by serum transferrin. The iron is delivered to... 

St-Pierre TG, Webb J, Mann S (1989) Ferritin and hemosiderin Stmctural and magnetic studies of the iron core. In Mann S, Webb J, Williams RJP (eds) Biomineralization—Chemical and Biochemical Perspectives. VCH Publishers, Weinheim, p 295-344... 

Iron is stored in the blood, liver, bone marrow, and spleen. The storage proteins for iron are ferritin and hemosiderin. With iron overload , more ferritin is synthesized in the liver to bind this excess iron. Iron is a cofactor for hemoglobin and cytochromes. 

Alternatively, free a(3 dimers may pass through the glomerular filter into the urine. The dimers are normally reabsorbed and catabolized by the proximal tubules and catabolized, with the iron incorporated into cellular ferritin and hemosiderin. Iron may reach toxic levels in the tubular... 

Most aspects of intermediary metabolism require essential trace elements in the form of metalloenzymes that have a range of catalytic properties. Specific metalloproteins are required for the transport and safe storage of very reactive metal ions, such as Fe or Cu. Examples are metaUo-thionein (Cu, Zn), transferrin, ferritin and hemosiderin (Fe), and ceruloplasmin (Cu). 

Iron is stored in the body in the form of ferritin and hemosiderin. 

Iron is in two special proteins, hemoglobin, which carries oxygen in the blood, and myoglobin, which stores oxygen in the muscles for future use. Iron itself is stored in proteins called ferritin and hemosiderin in the liver and heart muscle. Transferrin delivers iron to the tissues. 

The bulk of transferrin iron is delivered to immature erythroid cells for utilization in heme synthesis. Iron in excess of this requirement is stored as ferritin and hemosiderin. Unloading of iron to immature erythroid cells is by receptor-mediated endocytosis. The process begins in the clathrin-coated pits with the binding of diferric transferrin to specific plasma membrane transferrin receptors that are associated with the HFE protein complex. The next step is the internalization of the transferrin-transferrin receptor-HFE protein complex with formation of endosomes. The iron transporter DMTl present in the cell membrane is also internalized into the endosomes. In the endosomes, a proton pump acidifies the complex to pH 5.4, and by altering conformation of proteins, iron is released from transferrin bound to transferrin receptor... 

For ferric iron, the A assoc of deferoxamine is about 10 °, while the Tassoc for Ca " " is about 10. Iron in hemopro-teins is not affected by this agent, while the ferric iron of ferritin and hemosiderin is chelated in preference to that found in transferrin. Such selectivity makes the compound useful in treatment of iron storage problems and acute iron poisoning. 

Iron losses are about 1 mg daily through various excretions. It is noted that iron storage occurs in the form of ferritin and hemosiderin in the reticulo-enoth-lelian cells of the liver, spleen, and bone marrow, and in the parenchymal cells of the liver. 

Most normal body iron is contained either in hemoglobin or in the storage proteins ferritin and hemosiderin. Certainly for the heme proteins it is unlikely that chelating agents will be able to remove significant amounts of iron — and the iron in the storage proteins is also quite inaccessible. However, the high-spin Fe(III) in the iron transport protein transferrin is... 

In addition to the iron present in hemoglobin, there are three important iron storage proteins Phosvitin, Ferritin and Hemosiderin. Sub-varieties of these exist. 

In humans about 67% of iron is bound in hemoglobin, 25% in ferritin and hemosiderin (storage), about 4% in myoglobin, and 0.1% in Fe-containing enzymes. The important role of hemoglobin is uptake, transport, and release of oxygen. After absorption Fe is bound to specific transport proteins, the transferrins [17]. 

PROPERTIES OF FERRITIN AND HEMOSIDERIN PRESENT IN HEALTHY BRAIN TISSUE... 

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