Iron protein involving

Bacterial ferredoxins. Bacterial ferredoxin was first described in 1962 by Mortenson et al. (p who found a low-molecular iron protein involved in electron transfer of pyruvate hydrogenase and nitrogenase in C. pasteurianum. Subsequently, a number of ferredoxins have been found lii widely different types of bacteria such as photosynthetic bacteria and N2-fixing bacteria. These bacterial type ferredoxins have molecular... 

An elegant and efficient approach for the synthesis of structural models of carboxylate-rich non-heme dinuclear iron proteins involves the use of bulky ligands of the terphenyl carboxylate family [47, 48]. The resulting dinuclear iron(II) complexes can adopt two conformations, called the windmill and the paddlewheel motif (Scheme 2.9). 

The basic mechanism of nitrogenase with the use of dithionate as an electron donor for the iron protein involves the following steps (Thomeley and Lowe, 1985 Likhtenshtein, 1988a Burgess and Lowe, 1996 Smith, 1999 Seefeldt and Dean, 1997 Rees and Howard, 2000 Syrtsova and Timofeeva, 2001) 1) reduction of Fe-protein with flavodoxin or dithionate and attachment of two ATP molecules to the protein, 2) formation of a complex between the reduced FeP with two bound ATP molecules and FeMo-protein, 3) electron transfer between the reduced [Fe4S4] cluster of FeP to the P-cluster ofFeMoP coupled to the ATP hydrolysis, 4) electron transfer from P-cluster to... 

Peroxidases are heme-iron proteins involved in oxidative stress control. The mechanisms of this class of enzymes involve rather complex redox and electron transfer processes. These include alterations of spin state and ligands to the active-site heme as well as a novel role for Ca ions in the process as discussed by Moura and colleagues (Chapter 6). The topology and mechanism of the electron transfer process can be studied in detail using dynamic NMR data and molecular modeUng tools as illustrated by Pettigrew and co-workers (Chapter 7). The action of these types of peroxidases can be considered of crucial importance for the redox state regulation of the cell. 

Fe ". It was noted that the two-iron proteins involved localized valencies, with good evidence for... 

The most conspicuous use of iron in biological systems is in our blood, where the erythrocytes are filled with the oxygen-binding protein hemoglobin. The red color of blood is due to the iron atom bound to the heme group in hemoglobin. Similar heme-bound iron atoms are present in a number of proteins involved in electron-transfer reactions, notably cytochromes. A chemically more sophisticated use of iron is found in an enzyme, ribo nucleotide reductase, that catalyzes the conversion of ribonucleotides to deoxyribonucleotides, an important step in the synthesis of the building blocks of DNA. 

All these intermediates except for cytochrome c are membrane-associated (either in the mitochondrial inner membrane of eukaryotes or in the plasma membrane of prokaryotes). All three types of proteins involved in this chain— flavoproteins, cytochromes, and iron-sulfur proteins—possess electron-transferring prosthetic groups. 

Proteins involving iron have two major functions ... 

New information has been added in appropriate chapters on hpid rafts and caveolae, aquaporins, connexins, disorders due to mutations in genes encoding proteins involved in intracellular membrane transport, absorption of iron, and conformational diseases and pharmacogenomics. 

Figure 9.7 Iron transport by hepatocytes. Known proteins involved in iron transport across the plasma membrane of hapatocytes are represented. LMW = low molecular weight Trf = transferrin Trf-R = transferrin receptor HFE = hamochromatosis gene product 132m = 62-microglobulin 02-= superoxide OH- = hydroxyl radical FR = ferritin receptor SFT = stimulator of iron transport.

Three core oxidation states are known for protein-bound [Fe4-S4(S.Cys)4]3+ clusters as illustrated in Figure 2.9. Native proteins exhibit either the [Fe4-S4]2+ + or the [Fe4-S4]3+,2+ redox couple, with proteins involved in the latter couple being referred to historically as HiPIP (high-potential iron protein). The three oxidation states have not been traversed in one protein unless its tertiary structure is significantly perturbed. 

TfR is low in these patients, PIT is normal and most iron is stored in hepatocytes. In patients with hypoplastic anaemias and with transfusion iron overload, the BM cannot utilize iron, resulting in low TfR expression and decreased iron absorption. Quantitative analysis of all iron fluxes, which can be deduced from Figure 9.1, can assist in understanding the clinical expression of mutations of proteins involved in iron transport. 

Compounds that strongly chelate iron have been known for many years to stabilize HIF-la as well as upregulate proteins involved in red blood cell production erythropoietin (EPO), angiogenesis, vascular endothelial growth factor (VEGF), and iron transport. Some, but not all, of the pharmacological actions of iron chelators are produced by inhibition of PHD enzymes resulting in elevation of cellular HIF content. The action of selected iron chelators as they relate to PHD inhibition are briefly summarized here. 

Frataxin is the protein involved in Friedreich s ataxia, the most common ataxia found in man, associated with massive iron accumulation in mitochondria. 

There is one known pathway for cellular iron export, involving the export of iron into the plasma from the basolateral membrane of duodenal enterocytes, from macrophages, hepatocytes and a number of other cell types. This involves the protein known as IREG1 or ferroportin described already in Chapter 7. We will discuss ferroportin in more detail in the next section on iron homeostasis, since ferroportin is the target of hepcidin, a recently described iron regulatory peptide. 

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