Disease relevance of Fe+++

• Iron is essential to life, but poses severe problems because of its toxicity and the insolubility of hydrated ferric ions at neutral pH [1].
• We show that the ferric ion-binding protein from Neisseria gonorrhoeae (nFbp) readily binds clusters of Fe3+, Ti4+, Zr4+ or Hf4+ in solution [2].
• Pyochelin, an endogenous growth promoter that solubilizes ferric iron, has been isolated from Pseudomonas aeruginosa, including clinical strains [3].
• The first crystal structure of the iron-transporter ferric ion-binding protein from Haemophilus influenzae (hFBP), at 1.6 A resolution, reveals the structural basis for iron uptake and transport required by several important bacterial pathogens [4].
• These assays showed that NorR, a homolog of NO-responsive transcription factors in Ralstonia eutrophus, and Fur, the global repressor of ferric ion uptake, are major regulators of the response to reactive nitrogen species [5].

Psychiatry related information on Fe+++

• The fast process of contact binding is instantaneous with respect to instrument response time, is strongly exothermic for the N site and less so for the C site, and corresponds to binding of the chelated ferric ion [6].
• We prepose that the reductase of M. paratuberculosis represents an alternative strategy of mycobacteria to mobilize ferric iron and discuss its potential role in bacterial evasion of intracellular defense mechanisms [7].

High impact information on Fe+++

• Ferric iron accumulates in the cytosol of neurons and oligodendrocytes in distinctive regions of the brain [8].
• Iron homeostasis is typically regulated by cytoplasmic iron binding proteins, but here we describe a signal transduction system (PmrA/PmrB) that responds to extracytoplasmic ferric iron [9].
• Plasma iron circulates bound to transferrin (Trf), which solubilizes the ferric ion and attenuates its reactivity [10].
• Biological formation of methane is the terminal process of biomass degradation in aquatic habitats where oxygen, nitrate, ferric iron and sulphate have been depleted as electron acceptors [11].
• If iron bound to transferrin is the source of ferric ions for malaria parasites within mature erythrocytes, then the parasite must synthesize its own transferrin receptor and localize it on the surface of the infected cell, because the receptors for transferrin are lost during erythrocyte maturation [12].

Chemical compound and disease context of Fe+++

• Deferoxamine is widely used therapeutically as a chelator of ferric ion in disorders of iron overload [13].
• Upon iron limitation, Bacillus subtilis secretes the catecholic trilactone (2,3-dihydroxybenzoate-glycine-threonine)(3) siderophore bacillibactin (BB) for ferric iron scavenging [14].
• Mycobacterium tuberculosis mycobactins are mixed polyketide/nonribosomal peptides that contain a hydroxyaryloxazoline cap and two N-hydroxyamides that together create a high-affinity site for ferric ion [15].
• EPR spectroscopy has been successfully used to detect signals due to molybdenum (V) and ferric iron in intact cells of aerobically grown Paracoccus denitrificans [16].
• Two different types of purple bacteria, represented by strains L7 and SW2, were isolated which oxidized colorless ferrous iron under anoxic conditions in the light to brown ferric iron [17].

Biological context of Fe+++

• The results demonstrate that the observed hydrolysis of enterobactin is a necessary prerequisite to in vivo release of iron from the siderophore via ferric ion reduction [18].
• We describe here a family of biomimetic iron carriers that display high binding efficiency for ferric ions and favorable permeation properties across erythrocytic membranes [19].
• It is not yet understood to which part of the respiratory chain the reduction of ferric iron is linked [20].
• This result suggests that ligand escape is facilitated in this conformation, and blockage of the active site by water hinders immediate reassociation of NO to the ferric iron [21].
• The ferric iron chelator deferoxamine prevented cell death and totally quenched the DMPO-R signal with a 40% decrease in the DMPO-OH signal [22].

Anatomical context of Fe+++

• We report here that bones from the region of the sphenoid/ethmoid sinus complex of humans are magnetic and contain deposits of ferric iron [23].
• The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status [24].
• To test the hypothesis that the pathologic deposits of free ferric iron located on the inner aspect of sickle cell membranes would be redox active and promote oxidation of soluble oxyhemoglobin, we incubated native versus iron-stripped sickle or normal ghost membranes with oxyhemoglobin S [25].
• Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate [26].
• The fission yeast ferric reductase gene frp1+ is required for ferric iron uptake and encodes a protein that is homologous to the gp91-phox subunit of the human NADPH phagocyte oxidoreductase [27].

Associations of Fe+++ with other chemical compounds

• 1. We show here that NOS activity is decreased by about 50% in homogenates obtained from cells treated with interferon gamma plus lipopolysaccharide (IFN-gamma/LPS) in the presence of 50 microM ferric iron [Fe(3+)] as compared with extracts from cells treated with IFN-gamma/LPS alone [28].
• SFT, a stimulator of iron (Fe) transport, has been described as a transmembrane protein that facilitates the uptake of ferrous and ferric iron in mammalian cells [29].
• Ferric ions are essential for the biological activity of the hormone glycine-extended gastrin [30].
• Lignin peroxidase H2 (LiPH2) from the white rot fungus Phanerochaete chrysosporium catalyzed the reduction of cytochrome c, nitro blue tetrazolium, ferric iron, molecular oxygen, and triiodide in a reaction mixture containing LiPH2, H2O2, EDTA, and iodide [31].
• Thus the process of oxidative DNA damage requires only H(2)O(2), free iron, and an as-yet unidentified electron donor that reduces ferric iron to the ferrous state [32].

Gene context of Fe+++

• FRE1 and FRE2 encode cell surface metalloreductases that are required for reduction and uptake of free ferric iron [33].
• The high affinity iron uptake complex in the yeast plasma membrane (PM) consists of the ferroxidase, Fet3p, and the ferric iron permease, Ftr1p [34].
• The multicopper oxidase Fet3p is thought to convert extracellular ferrous iron to ferric iron, which then crosses the plasma membrane through the permease Ftr1p [35].
• The transferrins (TF) are a family of bilobal glycoproteins that tightly bind ferric iron [36].
• OX26, the Fab fragment of OX26 (50K mol. wt.), and Tf complexed to two ferric ions were conjugated to HRP irreversibly in a 1:1 molar ratio [37].

Analytical, diagnostic and therapeutic context of Fe+++

• Titration of the pink protein with one oxidizing equivalent of ferric ion also doubles the intensity of its g' = 1.74 EPR signal, again shifting the primary visible absorption band to 525 nm [38].
• Mössbauer spectroscopy shows that purple aconitase has high-spin ferric ions, each residing in a tetrahedral environment of sulfur atoms [39].
• Treatment of the membranes with proteinase K or thermolysin released phosphopeptides which were purified by ferric ion affinity chromatography and reverse phase high performance liquid chromatography [40].
• The hemoglobin oxidation Bohr effect is larger than the ligation Bohr effect, even when the former is corrected for any ionization of the water molecule bound to the ferric iron of methemoglobin [41].
• Here, the binding of ferric ion (chelated with a 2-fold molar ratio of nitrilotriacetate) to mTf has been studied using isothermal titration calorimetry and differential scanning calorimetry [42].

References