Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The copper binding tripeptide, glycyl-L-histidyl-L-lysine [GHK:Cu(II)] has a plethora of biological effects related to the wound healing process. The presence of iron complexes in damaged tissues is detrimental to wound healing, due to local inflammation, as well as microbial infection mediated by iron. To test if the wound healing properties of GHK:Cu(II) are due to an affect on iron metabolism, we examined the effects of GHK:Cu(II) on iron catalyzed lipid peroxidation. GHK:Cu(II) inhibited lipid peroxidation only if the iron source was ferritin. Whereas GHK:Cu(II) inhibited ferritin iron release it did not exhibit significant superoxide dismutase-like or ceruloplasmin-like activity. We propose that GHK:Cu(II) binds to the channels of ferritin involved in iron release and physically prevents the release of Fe(II). Thus, a biological effect of GHK:Cu(II), possibly related to wound healing, may be the inhibition of ferritin iron release in damaged tissues, preventing inflammation and microbial infections.
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PMID:Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation. 224 43

Immobilized metal ion affinity chromatography has been used to demonstrate and partially characterize Fe(III) binding sites on apoferritin. Binding of Fe(III) to these sites is influenced by pH, but not affected by high ionic strength. These results suggest that both ionic and coordinate covalent interactions are important in the formation of the Fe(III): apoferritin complex. This is, to our knowledge, the first demonstration of direct Fe(III) binding to apoferritin. Other immobilized metal ions, including Zn(II), Ni(II), Cu(II), Cr(III), Co(II), and Tb(III), displayed little or no adsorption of apoferritin. The analytical technique of immobilized metal ion affinity chromatography also shows great promise in the purification of apoferritin, ferritin, and other iron-binding proteins.
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PMID:Selective adsorption of apoferritin on immobilized Fe(III): demonstration of Fe(III) binding sites. 231 May 9

5-Hydroperoxymethyl-2'-deoxyuridine (HPMdU) is formed in DNA by ionizing radiation. Although relatively stable, HPMdU eventually decomposes to two products 5-hydroxymethyl-2'-deoxyuridine (HMdU) and 5-formyl-2'-deoxyuridine (FdU). We show that a number of transition metal ions and metalloproteins accelerate this process. Of the metal ions tested, Sn(II) and Fe(II) were the most active, with the former producing exclusively HMdU, and the latter, a mixture of both. Cu(I), Cu(II), Co(II), and Ni(II) induced a predominant generation of FdU, with copper ions being more effective than Co and Ni. FdU was also preferentially formed in the presence of the iron-containing proteins transferrin and ferritin, whereas HMdU was the major product in the presence of apotransferrin as well as in the presence of ceruloplasmin, a copper-containing protein.
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PMID:Decomposition of nucleoside hydroperoxide by metals and metalloproteins. 248 13

Both mammalian and bacterial ferritin undergo rapid reaction with small-molecule reductants, in the absence of Fe2+ chelators, to form ferritins with reduced (Fe2+) mineral cores. Large, low-potential reductants (flavoproteins and ferredoxins) similarly react anaerobically with both ferritin types to quantitatively produce Fe2+ in the ferritin cores. The oxidation of Fe2+ ferritin by large protein oxidants [cytochrome c and Cu(II) proteins] also occurs readily, yielding reduced heme and Cu(I) proteins and ferritins with Fe3+ in their cores. These latter oxidants also convert enthetically added Fe2+, bound in mammalian or bacterial apo- or holoferritin, to the corresponding Fe3+ state in the core of each ferritin type. Because the protein reductants and oxidants are much larger than the channels leading into the mineral core attached to the ferritin interior, we conclude that redox reactions involving the Fe2+/Fe3+ components of the ferritin core can occur without direct interaction of the redox reagent at the mineral core surface. Our results also suggest that the oxo, hydroxy species of the core, composed essentially of Fe(O)OH, arise exclusively from solvent deprotonation. The long-distance ferritin-protein electron transfer observed in this study may occur by electron tunneling.
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PMID:Redox reactivity of bacterial and mammalian ferritin: is reductant entry into the ferritin interior a necessary step for iron release? 284 7

Fortification of dairy products with trace metals requires use of assimilable compounds that do not catalyze off-flavors due to lipid peroxidation but show good biological availability. The Fe(III) and Cu(II) chelates of the promising chelator, lactobionic acid, have been compared to Fe(II) and Cu(II) salts for their ability to improve hematological status in a mildly anemic population. Fe- and Cu-fortified cow milk was administered to children (aged 6 to 15) in the Durango, Mexico, "school lunch" program. Children drank milk providing 20 mg Fe and 3 mg Cu as ferric/cupric lactobionate ("chelate") or ferrous/cupric chloride ("salt") for 5 of 7 days/wk for 3 months. Supplementation with "salt" and "chelate" raised Hb significantly by 1 and 0.3 g/dl, respectively, above the control (unsupplemented) group. No significant change was observed in incremental serum ferritin, serum Fe, or transferrin saturation, or in final serum Cu. Ferric lactobionate shows poorer bioavailability than ferrous ion in the presence of Cu, but milk can be an excellent vehicle for Fe or Cu supplementation.
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PMID:Bioavailability of iron- and copper-supplemented milk for Mexican school children. 689 32

The in vivo production of HO- requires iron ions, H2O2 and O2- or other oxidants but probably does not occur through the Haber-Weiss reaction. Instead oxidants, such as O2-, increase free iron by releasing Fe(II) from the iron-sulfur clusters of dehydratases and by interfering with the iron-sulfur clusters reassembly. Fe(II) then reduces H2O2, and in turn Fe(III) and the oxidized cluster are re-reduced by cellular reductants such as NADPH and glutathione. In this way, SOD cooperates with cellular reductants in keeping the iron-sulfur clusters intact and the rate of HO. production to a minimum. O2- and other oxidants can release iron from Fe(II)-containing enzymes as well as copper from thionein. The released Fe(III) and Cu(II) are then reduced to Fe(II) and Cu(I) and can then participate in the Fenton reaction. In mammalian cells oxidants are able to convert cytosolic aconitase into active IRE-BP, which increases the "free" iron concentration intracellularly both by decreasing the biosynthesis of ferritin and increasing biosynthesis of transferrin receptors. The biological role of the soxRS regulon of Escherichia coli, which is involved in the adaptation toward oxidative stress, is presumably to counteract the oxidative inactivation of the iron clusters and the subsequent release of iron with consequent increased rate of production of HO.
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PMID:The role of iron-sulfur clusters in in vivo hydroxyl radical production. 890 35

We have synthesized a novel six-coordinate metal chelator from the triamine cis-1,3,5-triaminocyclohexane by the addition of a 2-pyridylmethyl pendant arm on each nitrogen, which we term tachpyr. The experiments described here were designed to explore whether this compound exhibits potential antitumor activity. When added to MBT2 or T24 cultured bladder cancer cells, tachpyr was profoundly cytotoxic, with an IC50 of approximately 4.6 micromol/L compared with 70 micromol/L for desferioxamine. To explore the mode of action of tachpyr, several metal complexes were prepared, including Fe(II), Ca(II), Mn(II), Mg(II), Cu(II), and Zn(II) tachpyr complexes. Of these, the Zn(II), Cu(II), and Fe(II) complexes were without toxic effect, whereas the Ca(II), Mn(II), and Mg(II) complexes remained cytotoxic. To further probe the role of Zn(II) and Cu(II) chelation in the cytotoxicity of tachpyr, sterically hindered tachpyr derivatives were prepared through N-alkylation of tachpyr. These derivatives were unable to strongly bind Fe(III) or Fe(II) but were able to bind Zn(II) and Cu(II). When added to cells, these sterically hindered tachpyr derivatives were nontoxic, consistent with a role of iron depletion in the cytotoxic mechanism of tachpyr. Further, the addition of tachpyr to proliferating cultures resulted in an early and selective inhibition of ferritin synthesis, an iron storage protein whose translation is critically dependent on intracellular iron pools. Taken together, these experiments suggest that tachpyr is a cytotoxic metal chelator that targets intracellular iron, and that the use of tachpyr in cancer therapy deserves further exploration.
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PMID:Tumor cell cytotoxicity of a novel metal chelator. 969 27

Iron and copper are metals which play an important role in the living world. From a brief consideration of their chemistry and biochemistry we conclude that the early chemistry of life used water soluble ferrous iron while copper was in the water-insoluble Cu(I) state as highly insoluble sulphides. The advent of oxygen was a catastrophic event for most living organisms, and can be considered to be the first general irreversible pollution of the earth. In contrast to the oxidation of iron and its loss of bioavailability as insoluble Fe(III), the oxidation of insoluble Cu(I) led to soluble Cu(II). A new iron biochemistry became possible after the advent of oxygen, with the development of chelators of Fe(III), which rendered iron once again accessible, and with the control of the potential toxicity of iron by its storage in a water soluble, non-toxic, bio-available storage protein (ferritin). Biology also discovered that whereas enzymes involved in anaerobic metabolism were designed to operate in the lower portion of the redox spectrum, the arrival of dioxygen created the need for a new redox active metal which could attain higher redox potentials. Copper, now bioavailable, was ideally suited to exploit the oxidizing power of dioxygen. The arrival of copper also coincided with the development of multicellular organisms which had extracellular cross-linked matrices capable of resisting attack by oxygen free radicals. After the initial 'iron age' subsequent evolution moved, not towards a 'copper age', but rather to an 'iron-copper' age. In the second part of the review, this symbiosis of iron and copper is examined in yeast. We then briefly consider iron and copper metabolism in mammals, before looking at iron-copper interactions in mammals, particularly man, and conclude with the reflection that, as in Greek and Roman mythology, a better understanding of the potentially positive interactions between Mars (iron) and Venus (copper) can only be to the advantage of our species.
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PMID:Old iron, young copper: from Mars to Venus. 1150 52

Aminoacetone (AA) is a threonine and glycine catabolite long known to accumulate in cri-du-chat and threoninemia syndromes and, more recently, implicated as a contributing source of methylglyoxal (MG) in diabetes mellitus. Oxidation of AA to MG, NH(4)(+), and H(2)O(2) has been reported to be catalyzed by a copper-dependent semicarbazide sensitive amine oxidase (SSAO) as well as by Cu(II) ions. We here study the mechanism of AA aerobic oxidation, in the presence and absence of iron ions, and coupled to iron release from ferritin. Aminoacetone (1-7 mM) autoxidizes in Chelex-treated phosphate buffer (pH 7.4) to yield stoichiometric amounts of MG and NH(4)(+). Superoxide radical was shown to propagate this reaction as indicated by strong inhibition of oxygen uptake by superoxide dismutase (SOD) (1-50 units/mL; up to 90%) or semicarbazide (0.5-5 mM; up to 80%) and by EPR spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which detected the formation of the DMPO-(*)OH adduct as a decomposition product from the DMPO-O(2)(*)(-) adduct. Accordingly, oxygen uptake by AA is accelerated upon addition of xanthine/xanthine oxidase, a well-known enzymatic source of O(2)(*)(-) radicals. Under Fe(II)EDTA catalysis, SOD (<50 units/mL) had little effect on the oxygen uptake curve or on the EPR spectrum of AA/DMPO, which shows intense signals of the DMPO-(*)OH adduct and of a secondary carbon-centered DMPO adduct, attributable to the AA(*) enoyl radical. In the presence of iron, simultaneous (two) electron transfer from both Fe(II) and AA to O(2), leading directly to H(2)O(2) generation followed by the Fenton reaction is thought to take place. Aminoacetone was also found to induce dose-dependent Fe(II) release from horse spleen ferritin, putatively mediated by both O(2)(*)(-) and AA(*) enoyl radicals, and the co-oxidation of added hemoglobin and myoglobin, which may be viewed as the initial step for potential further iron release. It is thus tempting to propose that AA, accumulated in the blood and other tissues of diabetics, besides being metabolized by SSAO, may release iron and undergo spontaneous and iron-catalyzed oxidation with production of reactive H(2)O(2) and O(2)(*)(-), triggering pathological responses. It is noteworthy that noninsulin-dependent diabetes has been frequently associated with iron overload and oxidative stress.
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PMID:Aerobic oxidation of aminoacetone, a threonine catabolite: iron catalysis and coupled iron release from ferritin. 1155 49

The iron-storage protein ferritin encapsulates a nanoparticle of iron oxide. The size and properties of these nanoparticles can be adjusted by controlled oxidative hydrolysis reactions of Fe(II). This mineralized ferritin protein cage has previously been shown to act as an effective photocatalyst for reduction of Cr(VI). In the present work, we demonstrate that Fe(O)OH-mineralized ferritin catalyzes the photoreduction of Cu(II) to form a stable, air-sensitive, colloidal dispersion of Cu(0). In addition, the particle sizes of the Cu colloids can be controlled by varying the ratio of Cu(II) to ferritin. This illustrates an important principle, namely that the properties of one preformed material can be utilized for the specific synthesis of a second material, thus tailoring the desired physical properties of the final products. This procedure represents a multistep materials synthesis: the formation of a new nanomaterial from a catalytic precursor.
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PMID:Photocatalytic synthesis of copper colloids from CuII by the ferrihydrite core of ferritin. 1515 6


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