Protein ferritin

Although iron deficiency is a common problem, about 10% of the population are genetically at risk of iron overload (hemochromatosis), and elemental iron can lead to nonen2ymic generation of free radicals. Absorption of iron is stricdy regulated. Inorganic iron is accumulated in intestinal mucosal cells bound to an intracellular protein, ferritin. Once the ferritin in the cell is saturated with iron, no more can enter. Iron can only leave the mucosal cell if there is transferrin in plasma to bind to. Once transferrin is saturated with iron, any that has accumulated in the mucosal cells will be lost when the cells are shed. As a result of this mucosal barrier, only about 10% of dietary iron is normally absorbed and only 1-5% from many plant foods. 

C20-0105. The iron storage protein ferritin usuaiiy is neither empty of iron nor fiiied to capacity. Why is this situation advantageous for an organism ... 

A major contribution of the free-radical scavenging activity in blood plasma is attributable to the macro-molecular proteins (Wayner et al., 1985) of which albumin is a primary component and trapping agertt (Holt et al., 1984). Serum sulphydryl levels, primarily albumin-related, are decreased in subjects with rheumatoid complicated coalworkers pneumoconiosis, indicative of exacerbated inflammatory R.OM production (Thomas and Evans, 1975). Experimental asbestos inhalation in rats leads to an adaptive but evidendy insufficient response by an increase in endogenous antioxidant enzymes (Janssen etal., 1990). Protection of the vascular endothelium against iron-mediated ROM generation and injury is afforded by the iron sequestiant protein ferritin (Balia et al., 1992). 

Finally, animal, plant and microbial tissues have been shown to contain the iron storage protein ferritin. The animal protein has been extensively studied, but the mechanism of iron binding has not been completely resolved (29). Animal tissues contain, in addition, a type of granule comprised of iron hydroxide, polysaccharide and protein. The latter, called hemosiderin, may represent a depository of excess iron (30). Interestingly, a protein with properties parallel to those of ferritin has been found in a mold. Here the function of the molecule can be examined with the powerful tools of biochemical genetics (31). 

The core of the iron storage protein ferritin consists of a hydrated ferric oxide-phosphate complex. Various models have been proposed which feature Fe111 06 oct., Fe111 O4 tet. or Fe111 O4 tet. Fe111 06 oct. complexing the first listed is preferred by Gray (99) on the basis of the electronic absorption spectrum. The protein very closely related to ferritin which occurs in the mold Phycomyces blakesleeanus contains... 

Dentchev, T, Hahn, P, and Dunaief, JL, 2005. Strong labeling for iron and the iron-handling proteins ferritin and ferroportin in the photoreceptor layer in age-related macular degeneration. Arch Ophthalmol 123, 1745-1746. 

In the absence of a demonstrable yeast iron-storage protein (ferritin), we have to recognize that, despite our substantial advances in understanding iron uptake in yeast, we know practically nothing about intracellular iron metabolism - except that is for iron transport into, and out of, mitochondria. 

The iron storage protein ferritin is a small 20 kDa a-helical protein that spontaneously assembles into a hollow ball-like homo-24-mer. The outer diameter of the sphere is circa 12 nm and the inner diameter, or core diameter, is circa 8 nm. A smaller version, known as miniferritin or Dps protein (Dps = DNA protecting... 

There are many other proteins that contain iron in a form that is neither in haem nor in iron-sulfur clusters. We have already encountered the iron storage and transport proteins, ferritin and transferrin (see Chapter 8). We propose to discuss here two other classes of iron-containing proteins, those with mononuclear non-haem iron centres and those with dinuclear non-haem iron centres. 

Once in the serum, aluminium can be transported bound to transferrin, and also to albumin and low-molecular ligands such as citrate. However, the transferrrin-aluminium complex will be able to enter cells via the transferrin-transferrin-receptor pathway (see Chapter 8). Within the acidic environment of the endosome, we assume that aluminium would be released from transferrin, but how it exits from this compartment remains unknown. Once in the cytosol of the cell, aluminium is unlikely to be readily incorporated into the iron storage protein ferritin, since this requires redox cycling between Fe2+ and Fe3+ (see Chapter 19). Studies of the subcellular distribution of aluminium in various cell lines and animal models have shown that the majority accumulates in the mitochondria, where it can interfere with calcium homeostasis. Once in the circulation, there seems little doubt that aluminium can cross the blood-brain barrier. 

In its morphology the isolated polymer is strikingly similar to the inner core of the iron storage protein ferritin. This core, which is surrormd-ed by protein subunits, is a hydroxy-iron phosphate polymer, with 0.11 phosphate atoms per iron. It is a sphere 74 A in diameter and contains about 2000 iron atoms 35). 

A dipeptide Met- , derived from sardine muscle (Matsufuji et ah, 1994), stimulates expression of the antioxidant defense protein HO-1 in a concentration-dependent manner. Previous findings revealed that HO-1 protein expression is accompanied by the induction of a secondary antioxidant protein, ferritin. In a present study, the effect of Met- on the expression of the antioxidant stress proteins, heme oxygenase-1 (HO-1), and ferritin in endothelial cells derived from the human umbilical vein and their contribution to the decrease in radical formation that occurs under the influence of this dipeptide were studied and reported potential activity (Erdmann et ah, 2006). 

Within tissues of animals, plants, and fungi much of the iron is packaged into the red-brown water-soluble protein ferritin, which stores Fe(III) in a soluble, nontoxic, and readily available form.61 64 Although bacteria store very little iron,65 some of them also contain a type of ferritin.66-67 On the other hand, the yeast S. cerevisieae stores iron in polyphosphate-rich granules, even though a ferritin is also present.65 Ferritin contains 17-23% iron as a dense core of hydrated ferric oxide 7 nm in diameter surrounded by a protein coat made up of twenty-four subunits of mo-... 

Ascorbate can also serve as a signal. In cultured cells, which are usually deficient in vitamin C, addition of ascorbate causes an enhanced response to added iron, inducing synthesis of the iron storage protein ferritin.11 Ascorbate indirectly stimulates transcription of procollagen genes 1 and decreases secretion of insulin by the pancreas.)) However, since its concentration in blood is quite constant this effect is not likely to cause a problem for a person taking an excess of vitamin C. 

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. 

As an example of information encoding, consider the iron-storage protein ferritin. The protein comprises 24 identical subunits that, together, form a nearly spherical shell of octahedral symmetry. Why 24 subunits, and why octahedral symmetry Examination of the individual subunits... 

Storage These provide a store of substances required by the body. For example, the protein ferritin acts as an iron store for the body. 

The automated system of the particle counting immunoassay is now commercially available as the product impact (Immunoassay by Particle Counting), which can measure C-reactive protein, ferritin, human placental lactogen, thyroxine, a-fetoprotein (C7), IgE (M2), digoxin (C6), somatotropin (C5), and others. 

As mentioned above, there are the profound relationships between Al and Fe metabolism in mammalian cells Al can bind proteins bound to Fe. Apo-Tf binds to Al to form di-Al-Tf (Al2Tf). Al2Tf is recognized by TfR to be taken up by brain cells. Al binds Fe storage protein, ferritin and also influences the expression of ferritin mRNA. If this is a reliable phenomenon, Al is required to interact with IRPs which post-trascriptionally regulate the expression of ferritin or TfR mRNAs. 

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