Iron protein release

The haem molecule would be incomplete without iron so this must be delivered to the progenitor red cells. Iron is toxic so it is carried in the plasma bound to a specific protein named transferrin (Tf). Uptake of iron is via a Tf receptor, of which there are approximately 300 000 per cell. The whole iron/Tf complex is taken into the cell by endocytosis where the iron is released and made available for incorporation into the porphyrin ring by ferrochelatase. 

Iron (Fe " ) released from hemoglobin in the histiocytes is bound to ferritin and then transported in the blood by transferrin, which can deliver it to tissues for synthesis of heme. Important proteins in this context are ... 

The free iron in the food enters the intestinal mucus from which it is absorbed by the epithelial cells via a transporter protein. This absorption is decreased by tea, coffee and phytate (inositol hexaphosphate) present in cereal fibre. Iron combined in haem is absorbed directly by epithehal cells after being released from haem-containing protein. The free iron is released in these cells by the enzyme haem oxidase. The free Fe is then bound to paraferritin and released into the blood where it is bound by ferritin. The three reactions are as follows. 

The protein that transports iron around the body in blood and lymph, and indeed within the cell, is transferrin (500 kDa). It has two binding sites for iron (Fe " ) when no iron is bound, it is known as apotransferrin. Transferrin picks up not only the iron absorbed from the intestine but also that released from the macrophages and then transports it to the cells that require it, which is primarily the cells in the bone marrow but also other cells that are proliferating. For uptake into the cells, the transferrin binds to a receptor on the plasma membrane and then the complex enters the cell by endocytosis. The iron is released from the complex in the cytosol where it is bound by the intra-... 

Once the siderophore-iron complexes are inside the bacteria, the iron is released and utilized for vital cell functions. The iron-free hydroxamate siderophores are commonly re-excreted to bring in an additional iron load (Enterobactin is at least partially degraded by a cytoplasmic esterase This cycle is repeated until specific intracellular ferric uptake regulation proteins (Fur proteins) bind iron, and signal that the intracellular iron level is satisfactory, at -which point ne-w siderophore and siderophore-receptor biosynthesis are halted and the iron-uptake process stops. This intricate feedback mechanism allows a meticulous control over iron(III) uptake and accumulation against an unfavorable concentration gradient so as to maintain the intracellular iron(III) level within the required narrow window. Several excellent reviews concerning siderophore-iron transport mechanisms have been recently published i.3,i6, is,40,45,60-62 ... 

A biological example of E° is the reduction of Fe(III) in the protein transferrin, which was introduced in Figure 7-4. This protein has two Fe(III)-binding sites, one in each half of the molecule designated C and N for the carboxyl and amino terminals of the peptide chain. Transferrin carries Fe(III) through the blood to cells that require iron. Membranes of these cells have a receptor that binds Fe(III)-transferrin and takes it into a compartment called an endosome into which H is pumped to lower the pH to —5.8. Iron is released from transferrin in the endosome and continues into the cell as Fe(II) attached to an intracellular metal-transport protein. The entire cycle of transferrin uptake, metal removal, and transferrin release back to the bloodstream takes 1-2 min. The time required for Fe(III) to dissociate from transferrin at pH 5.8 is —6 min, which is too long to account for release in the endosome. The reduction potential of Fe(IH)-transferrin at pH 5.8 is E° = —0.52 V, which is too low for physiologic reductants to reach. 

A second group of electron carriers in mitochondrial membranes are the iron-sulfur [Fe-S] clusters which are also bound to proteins. Iron-sulfur proteins release Fe3+ or Fe2+ plus H2S when acidified. The "inorganic clusters" bound into the proteins have characteristic compositions such as Fe2S2 and Fe4S4. The sulfur atoms of the clusters can be regarded as sulfide ions bound to the iron ions. The iron atoms are also attached to other sulfur atoms from cysteine side chains from the proteins. The Fe-S proteins are often tightly associated with other components of the electron transport chain. For example, the flavoproteins Flavin 1, Flavin 2, and Flavin 3 shown in Fig. 10-5 all contain Fe-S clusters as does the Q-cytochrome b complex. All of these Fe-S clusters seem to be one-electron carriers. 

Another interesting cluster conversion is the joining of two Fe2S2 clusters in a protein to form a single Fe4S4 cluster at the interface between a dimeric protein. Such a cluster is present in the nitrogenase iron protein (Fig. 24-2) and probably also in biotin synthase.294 The clusters in such proteins can also be split to release the monomers. 

Each P-cluster is actually a joined pair of cubane-type clusters, one Fe4S4 and one Fe4S3 with two bridging cysteine -SH groups and one iron atom bonded to three sulfide sulfur atoms (Fig. 24-3).17/23 The FeMo-coenzyme can be released from the MoFe-protein by acid denaturation followed by extraction with dimethylformamide.24 While homocitrate was identified as a component of the isolated coenzyme, the three-dimensional structure of FeMo-co was deduced from X-ray crystallography of the intact molybdenum-iron protein.14/17/18... 

When NADH is consumed, 02 release and the initial nitroxide concentration are restored. When transferring between two oxidized states of myoglobine (MbFem and MbFeIV), nitroxide and oxo-ammonium cation manifest catalase-mimetic activity of MbFem, hence, promoting () dismutation accompanied by 02 release and protecting from highly valent iron proteins ... 

Cold-set whey protein gels obtained by addition of calcium ions to preheated whey proteins have been used to deliver iron (Remondetto et al. 2002). By modulating the conditions of formation, gels with different microstructures (particulate or filamentous) were formed with different encapsulating properties. Filamentous whey protein gels were more efficient than particulate gels in delivering bioavailable iron to the intestine, as less iron was released at acidic but more at alkaline pH (Remondetto et al. 2004). 

Bacteria without an OM, such as Gram-positives, do not rely on OM receptors or periplasmic binding proteins for siderophore uptake. Instead, extracellular ferric siderophores are bound by CM-anchored binding proteins that are similar to the periplasmic binding proteins, which then interact with ABC-type transport complexes similar to those employed by Gram-negative bacteria. Once internalized, iron is released from ferric siderophores by the activities of specific cytosolic esterases or reductases. 

It is well established that the form of iron in food also affects its availability for absorption. Inorganic forms of iron and iron-protein compounds need to be reduced to the ferrous state and released from conjugation for effective absorption (3) Since most food iron is in the form of ferric (Fe+++) salts, these must be reduced to be efficiently absorbed (2). Similarly, ferrous (Fe++) salts are used preferentially to ferric salts in the treatment of iron deficiencies (1). 

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