Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. During pathological states of iron-overload or oxidant stress, low-molecular-mass iron can become available within extracellular fluids. 2. This iron would be converted to the ferrous state were it not for the protective anti-oxidant protein caeruloplasmin. 3. The ferrous-ion-oxidizing activity of caeruloplasmin rapidly converts ferrous ions back to the less reactive ferric state so that they can bind to available binding sites on transferrin. 4. Cerebrospinal fluids, however, often appear to contain low-molecular-mass iron, high levels of ascorbate and low levels of ferroxidase activity with little or no iron-binding capacity. 5. When iron ions are present in cerebrospinal fluid they are therefore likely to be in the ferrous state. 6. The development and application of an assay to speciate and measure ferrous ions in simple aqueous solution and their redox cycling activity in biological fluids is described.
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PMID:Ferrous ions detected in cerebrospinal fluid by using bleomycin and DNA damage. 137

The paper presents an experimental model of toxic influenza infection. The toxic form of influenza was shown to result in the activation of free radical processes accompanied by the accumulation of both lipid peroxidation products and methemoglobin and the decrease of alpha-tocopherol in erythrocytes, by the accumulation of NO. and nitrizyl complexes of heme iron in the blood. The activation of free radical processes was followed by the stimulation of antioxidant system in the blood. Thus, there was an increase of both superoxide dismutase activity in erythrocytes and ceruloplasmin content in the blood. The data obtained support the important role of the active products of free radical processes in the development of toxicosis under acute virus infections.
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PMID:[Activation of free radicals reaction and changes in the state of antioxidant protection in blood in toxic experimental influenza infection]. 142 5

The ferritins of animals and plants and the bacterioferritins (BFRs) have a common iron-storage function in spite of differences in cytological location and biosynthetic regulation. The plant ferritins and BFRs are more similar to the H chains of mammals than to mammalian L chains, with respect to primary structure and conservation of ferroxidase center residues. Hence they probably arose from a common H-type ancestor. The recent discovery in E. coli of a second type of iron-storage protein (FTN) resembling ferritin H chains raises the question of what the relative roles of these two proteins are in this organism. Mammalian L ferritins lack ferroxidase centers and form a distinct group. Comparison of the three-dimensional structures of mammalian and invertebrate ferritins, as well as computer modeling of plant ferritins and of BFR, indicate a well conserved molecular framework. The characterisation of numerous ferritin homopolymer variants has allowed the identification of some of the residues involved in iron uptake and an investigation of some of the functional differences between mammalian H and L chains.
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PMID:Structure, function, and evolution of ferritins. 143 78

A 55-year-old female with progressed dementia, cerebellar ataxia was reported. There was no family history of the same symptoms although her brothers, sisters and a son showed hypoceruloplasminemia and decrease of the serum copper content. On physical examination, anemia, dementia, dysarthria, torticollis, choreic involuntary movement of respiratory muscles, hyperreflexia in extremities and cerebellar ataxia were noted. Blood analysis revealed microcytic hypochromic anemia, diabetes mellitus, decrease of copper content of the serum and urine. Serum ferritin concentration was increased. Serum ceruloplasmin could not be detected. Biopsy of the liver showed that copper content in the liver was slightly increased and iron content was remarkably increased. On MRI study, dentate nucleus of the cerebellum, the thalamus, the putamen and the caudate nucleus and the liver showed low intensity in both T1 and T2 weighted images. Based on increased iron content in the liver, the radiological findings of the brain suggested deposition of iron in the brain. This deposition was considered as caused by deficiency of function of ceruloplasmin as ferroxidase. This disorder is suggested as a new disease due to ceruloplasmin deficiency different from Wilson's disease.
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PMID:[A case of ceruloplasmin deficiency which showed dementia, ataxia and iron deposition in the brain]. 145 25

Protein ferroxidase site(s), which catalyze the reaction between ferrous ion and dioxygen, have long been thought to play a role in core formation in ferritin; however, the mechanism of the reaction has never been studied in detail. In the present work, the enzymatic activity of ferritin was examined using oximetry, the net Fe2+ oxidation reaction being as follows. [formula: see text] The reaction exhibits saturation kinetics with respect to both Fe2+ and O2 (apparent Michaelis constants: Km,Fe = 0.35 +/- 0.01 mM and Km,O2 = 0.14 +/- 0.03 mM). The enzyme has a turnover number kcat = 80 +/- 3 min-1 at 20 degrees C with maximal activity at pH 7. The kinetics are discussed in terms of two mechanisms, one involving monomeric and the other dimeric iron protein complexes. In both instances Fe(II) oxidation occurs in 1-electron steps. Zinc(II) is a competitive inhibitor of iron(II) oxidation at Zn2+/apoprotein ratios > or = 6 (inhibitor constant KI,Zn = 0.067 +/- 0.011 mM) but appears to be a noncompetitive inhibitor at lower ratios (< or = 2), indicating the presence of more than one type of zinc binding site on the protein. At increments of 50 Fe2+/protein or less, all of the iron is oxidized via the protein ferroxidase site(s), independent of the amount of core already present. However, when larger increments are employed, some iron oxidation appears to occur on the surface of the mineral core. The results of these studies emphasize the role of the protein shell in all phases of core growth and confirm the presence of a functionally important catalytic site in ferritin in addition to other binding sites on the protein for iron.
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PMID:Ferroxidase kinetics of horse spleen apoferritin. 146 15

The ability to incorporate iron in vitro was studied in homopolymers of human ferritin L-chain, human ferritin H-chain and its variants and in homopolymer mixtures. The H-chain variants carried amino acid substitutions in the ferroxidase centre and/or in carboxy residues on the cavity surface. Iron incorporation was examined by gel electrophoresis of the reaction products by staining for iron and protein. It was found that inactivation of the ferroxidase centre combined with the substitution of four carboxy groups on the cavity abolished the ability of H-chain ferritin to incorporate iron. Competition experiments with limited amounts of iron showed that, at neutral pH, L-chain ferritin is more efficient in forming iron cores than the H-chain variants altered at the ferroxidase activity or in the cavity. Competition experiments at pH 5.5 demonstrated that L-chain apoferritin is able to incorporate iron only when in the presence of H-chain variants with ferroxidase activity. The results indicate that L-chain apoferritin has a higher capacity than the H-chain apoferritin to induce iron-core nucleation, whereas H-chain ferritin is superior in promoting Fe(II) oxidation. The finding of cooperative roles of the H- and L-chains in ferritin iron uptake provides a clue to understanding the biological function of isoferritins.
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PMID:Evidence of H- and L-chains have co-operative roles in the iron-uptake mechanism of human ferritin. 146 63

The iron storage protein, ferritin, is widely distributed in the living kingdom. Here the complete cDNA and derived amino-acid sequence of pea seed ferritin are described, together with its predicted secondary structure, namely a four-helix-bundle fold similar to those of mammalian ferritins, with a fifth short helix at the C-terminus. An N-terminal extension of 71 residues contains a transit peptide (first 47 residues) responsible for plastid targetting as in other plant ferritins, and this is cleaved before assembly. The second part of the extension (24 residues) belongs to the mature subunit; it is cleaved during germination. The amino-acid sequence of pea seed ferritin is aligned with those of other ferritins (49% amino-acid identity with H-chains and 40% with L-chains of human liver ferritin in the aligned region). A three-dimensional model has been constructed by fitting the aligned sequence to the coordinates of human H-chains, with appropriate modifications. A folded conformation with an 11-residue helix is predicted for the N-terminal extension. As in mammalian ferritins, 24 subunits assemble into a hollow shell. In pea seed ferritin, its N-terminal extension is exposed on the outside surface of the shell. Within each pea subunit is a ferroxidase centre resembling those of human ferritin H-chains except for a replacement of Glu-62 by His. The channel at the 4-fold-symmetry axes defined by E-helices, is predicted to be hydrophilic in plant ferritins, whereas it is hydrophobic in mammalian ferritins.
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PMID:Amino-acid sequence and predicted three-dimensional structure of pea seed (Pisum sativum) ferritin. 147 6

In 71 patients with fever and bacteremia without complications, a prospective study of acute-phase reactants is done. Raises in haptoglobin, ceruloplasmin, alpha-1-antitrypsin, protein C, beta-2-microglobulin, IgA and ferritin serum levels, together with leucocytosis and GSR, were very significant when diagnosis was done. Fibronectin, sideremia and transferrin were lowered. After 3 and 6 days of treatment haptoglobins, alpha-1-antitrypsin, protein C, ferritin, leucocytosis and GSR are lowered, while immunoglobulins, sideremia, transferrin and fibronectin raised, the latter until normalization. Fibronectin as well as changes in iron metabolism were very reliable parameters of inflammation and favorable evolution.
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PMID:[Acute-phase reactants in sepsis]. 148 35

We have found transition metals tightly bound to apolipoprotein A-I-containing lipoproteins [Lp(A-I)] isolated by selected affinity immunosorption from human serum. Prominent among the metal ions detected were iron and copper. By immunoblotting the proteins of Lp(A-I), we detected both transferrin and ceruloplasmin. The transferrin-containing Lp(A-I) particles, isolated by selected affinity immunosorption against transferrin, were larger (mean diameter of 14.2 nm) and had a higher protein content than most high density lipoproteins (HDL). Ultracentrifugally isolated HDL were found to contain much less transferrin, whereas transferrin was found associated with apolipoprotein A-I from the greater than 1.21-g/ml ultracentrifugal fraction. This suggests that the complex is not recovered in the classic HDL density interval because of its very high density. HDL inhibit copper-catalyzed oxidation of low density lipoproteins (LDL) in vitro. We have found that immunoisolated Lp(A-I) are an order of magnitude more effective in inhibiting the oxidation of LDL than ultracentrifugally isolated HDL, on the basis of protein mass. When the Lp(A-I) particles containing transferrin and ceruloplasmin were removed from the bulk of Lp(A-I), inhibition of the in vitro oxidation of LDL was significantly decreased.
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PMID:Binding of transition metals by apolipoprotein A-I-containing plasma lipoproteins: inhibition of oxidation of low density lipoproteins. 149 91

The ability of plasma from newborn babies (cord blood) and adults to inhibit iron-induced lipid peroxidation was compared. The caeruloplasmin and transferrin concentrations, and latent iron-binding capacity were lower in the babies (p less than 0.001). The plasma of many of the babies had no latent iron-binding capacity and contained non-protein-bound iron (measured by the bleomycin assay). The in vitro ability of plasma to inhibit iron-induced liposome peroxidation by either ferroxidase antioxidant activity (caeruloplasmin) or iron-binding antioxidant activity (transferrin) was measured. The antioxidant activity in both assays was decreased in the babies (p less than 0.001). The percentage inhibition of peroxidation in the iron-binding antioxidant assay correlated positively with the latent iron-binding capacity (p less than 0.001) and negatively with the presence of bleomycin-detectable iron (p less than 0.02) in the babies. This assay produced stimulation of peroxidation in 42% of the babies but none of the adults. The diminished capacity of cord blood plasma to prevent iron-induced lipid peroxidation may predispose the newborn baby to the toxic effects of oxygen.
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PMID:Limited protection against iron-induced lipid peroxidation by cord blood plasma. 150 87


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