Disease relevance of iron

• This approach to the use of an insoluble electron acceptor may explain why Geobacter species predominate over other Fe(III) oxide-reducing microorganisms in a wide variety of sedimentary environments [1].
• Fe(III)-reducing microorganisms in the genus Shewanella have resolved this problem by releasing soluble quinones that can carry electrons from the cell surface to Fe(III) oxide that is at a distance from the cell [1].
• Surprisingly, even Thermotoga maritima, previously considered to have only a fermentative metabolism, could grow as a respiratory organism when Fe(III) was provided as an electron acceptor [2].
• Therefore, we studied the effects of experimental iron overload on hepatocyte lysosomal structure, physicochemical properties, and function in rats fed carbonyl iron [3].
• One of the two nonidentical subunits of Escherichia coli ribonucleotide reductase, protein B2, contains in its active form two antiferromagnetically coupled Fe(III) ions and an organic free radical that arises by the one-electron oxidation of tyrosine-122 of the polypeptide chain [4].

Psychiatry related information on iron

• Abeta binds Zn(2+), Cu(2+), and Fe(3+) in vitro, and these metals are markedly elevated in the neocortex and especially enriched in amyloid plaque deposits of individuals with Alzheimer's disease (AD) [5].
• It subsequently decays within 10 s to form a mu-oxodiFe(III)-protein complex (species D), which partially vacates the ferroxidase sites of the protein to generate Fe(III) clusters (species C) at a reaction time of 10 min [6].

High impact information on iron

• Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied [7].
• Geobacter metallireducens accesses insoluble Fe(III) oxide by chemotaxis [1].
• Our results suggest that increasing the bioavailability of Fe(III) by adding suitable ligands provides a potential alternative to oxygen addition for the bioremediation of petroleum-contaminated aquifers [8].
• Plasma transferrins are monomeric glycoproteins with a molecular weight of approximately 80,000 (ref. 2); they have two similar and very strong binding sites for Fe(III), together with two associated anion binding sites [9].
• Because imidazole compounds such as histamine can interact with Fe(III) heme proteins, we investigated whether such substances could interact with Rhodnius nitrophorins [10].

Chemical compound and disease context of iron

• Both parenteral ferric nitrilotriacetate (FeNTA) administration and dietary supplementation with carbonyl iron were used to produce chronic iron overload [11].
• Single doses of 1,000 to 10,000 mg of carbonyl iron (15 to 150 times the 65 mg of iron in the usual dose of ferrous sulfate) were tolerated by nonanemic volunteers with no evidence of toxicity and only minor gastrointestinal side effects [12].
• Hepatic mitochondrial oxidative metabolism and lipid peroxidation in experimental hexachlorobenzene-induced porphyria with dietary carbonyl iron overload [13].
• We have previously shown that human Abeta has the ability to reduce Fe(III) and Cu(II) and produce hydrogen peroxide coupled with these metals, which is correlated with toxicity against primary neuronal cells [14].
• Complexes of Fe(III) and ATP similar to those described here may form in vivo either as normal components of intracellular iron metabolism or during iron excess where the consequent alteration of free nucleotide triphosphate pools could contribute to the observed toxicity of iron [15].

Biological context of iron

• Here we report that adding organic ligands that bind to Fe(III) dramatically increases its bioavailability, and that in the presence of these ligands, rates of degradation of aromatic hydrocarbons in anoxic aquifer sediments are comparable to those in oxic sediments [8].
• We investigated whether lipid peroxidation occurred in rats fed a diet containing 3% carbonyl iron for 5-13 wk, and if this resulted in the formation of MDA- and 4-HNE- protein adducts [16].
• ADCC activity was found primarily in the plastic nonadherent cell population and was greatly enriched following removal of phagocytic cells by carbonyl iron [17].
• Carbonyl iron had no effect on blood alcohol concentration, hepatic biochemical measurements, or liver histology in control animals [18].
• Iron (Fe) is critical for cell-cycle progression and DNA synthesis and potentially represents a novel molecular target for the design of new anticancer agents [19].

Anatomical context of iron

• Removal of macrophages from adherent splenocytes by either carbonyl-iron incubation or passage through Sephadex G-10 columns did not affect their synergistic function [20].
• Pretreatment of spleen cells with carbonyl iron and a magnet did not abrogate the suppressor cell function [21].
• Two new techniques were developed that separate monocytes into M1 + M2 and M3 fractions; one used preferential incorporation of carbonyl iron particles by M3 cells and the other used the selective aggregation of M3 cells by thrombin in the presence of platelets [22].
• These studies have examined the role of iron in intact hepatocytes using cells from rats fed an iron-deficient diet, a control diet or a diet containing 3% carbonyl iron [23].
• The isolated membranes contributed to the reduction of anthracycline-bound Fe(III) and probably represented the main determinant of lipid peroxidation by iron-Dnr [24].

Associations of iron with other chemical compounds

• Superoxide dismutase activity, glutathione peroxidase activity, and reduced glutathione concentrations, together with malondialdehyde production, were measured in the livers of rats chronically iron-overloaded by (a) parenteral iron (primarily Kupffer cell iron deposition) and (b) dietary carbonyl iron (mainly parenchymal iron deposition) [25].
• First, MAC1 is involved in basal level transcription of FRE1, encoding a plasma membrane component associated with both Cu(II) and Fe(III) reduction [26].
• The rationalization of this fact, and the possible explanation of a great accumulation of spectroscopic data, is that cytochrome a3 may be a two-electron redox center, with stable Fe(IV), Fe(III), and Fe(II) states during its redox cycle [27].
• An independent hypothesis holds that in Cryptococcus neoformans, an important function of the melanizing enzyme (apart from melanization) is the oxidation of Fe(II) to Fe(III), thereby forestalling generation of the harmful hydroxyl radical from H(2)O(2) [28].
• A model for the structure of this inhibitor-enzyme complex is proposed in which the 5-androstene ring system of the steroid occupies the substrate binding site, and the amine group of the side chain occupies an axial coordination position of the Fe(III) center [29].

Gene context of iron

• Fet3, the apparent ferroxidase, is proposed to facilitate iron uptake by catalyzing the oxidation of reductase-generated Fe(II) to Fe(III) by O2; in this model, Fe(III) is the substrate for the iron permease, encoded by FTR1 (Kaplan, J., and O'Halloran, T. V. (1996) Science 271, 1510-1512) [30].
• Elevated Fe(III) reduction was also observed in all FRE2 and some FRE1 lines [31].
• Damage to mitochondria plays a role in the CYP2E1-dependent toxicity of Fe + AA, because the mitochondrial transmembrane potential decreased early in the process, and cyclosporin A prevented the toxicity [32].
• Lung sections from rats exposed to crocidolite or chrysotile (but not from sham-exposed rats nor from rats exposed to "inert" carbonyl iron particles) demonstrated strong immunoreactivity for nitrotyrosine and phospho-ERK1/2 in alveolar macrophages and bronchiolar epithelium [33].
• EDTA prevented inactivation of Fru-P2ase, G6PD and LDH by ascorbate/Cu(II) and of Fru-P2ase by ascorbate/Fe(III) suggesting a site-specific oxidation catalyzed by a protein-bound metal ion [34].

Analytical, diagnostic and therapeutic context of iron

• Internal electron transfer from the [(NH3)5RuII-] centre to the Fe(III) haem centre occurs with a rate constant k congruent to 53 s-1 (25 degrees C) (delta H = 3.5 kcal mol-1, delta S = -39 EU), as measured by pulse radiolysis [35].
• The nature of bonding interactions between Fe(III) and NO in the ferric nitrosyl complexes of myoglobin (Mb), hemoglobin A (HbA), and horseradish peroxidase (HRP) is investigated by Soret-excited resonance Raman spectroscopy [36].
• Gel electrophoretic mobility-shift assays show that Fe(2+) and not Fe(3+) activates DtxR for DNA binding [37].
• Treatment of lymphocyte preparations with carbonyl iron and magnetic separation to remove phagocytic cells or treatment with complement-coated red cells followed by repeated gradient centrifugation to remove complement receptor-bearing lymphocytes did not reduce the granulocytotoxicity [38].
• In contrast, the active Fe(II) + CO forms of both wild-type and M124R CooA are six-coordinate and low-spin with a protein ligand other than Cys(75), so that WT and Fe(III) M124R CooA are apparently achieving an active conformation despite two different heme coordination and ligation states [39].

References