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At least 19 recordsLinked to original sources
PubMed1977

Dissociation and reconstitution of human ferroxidase II.

The ferroxidase II protein from human serum is large and structurally complex. It possesses protein-bound lipid and copper components which are essential for the maintenance of its catalytic activity. Treatment of ferroxidase II with 8 M urea, 6 M guanidine hydrochloride, or 6 M guanidine hydrochloride and alkylation does not result in the dissociation of the enzyme into subunits. However, treatment with sodium dodecyl sulfate results in the dissociation of ferroxidase II into two nonidentical subunits, designated S-I and S-II. S-I contains little phospholipid, cholesterol, or copper and has a molecular weight of 3.8-3.9 X 10(5). In contrast, S-II contains bound phospholipid, cholesterol, and copper and has a molecular weight of 2.2-2.4 X 10(5). The lipid compositon of S-II is identical with the native enzyme. Sodium dodecyl sulfate-free S-I exhibits no ferroxidase activity. Immediately following removal of sodium dodecyl sulfate, S-II exhibits ferroxidase activity but S-II rapidly loses its activity in the absence of S-I. The separated subunits spontaneously reassociate upon removal of the sodium dodecyl sulfate to yield a fully active enzyme which chemically appears identical with native ferroxidase II. Furthermore, the reconstituted enzyme is stable. Both native and reconstituted ferroxidase II may be stored at 4 degrees C for 6 weeks without any loss in activity. This suggests that S-II, the copper and lipid-containing subunit, is the catalytic subunit and that S-I is essential for the stabilization of the enzymic activity of S-II. These results provide insight into the molecular structure and chemical composition of ferroxidase II and suggest that the complete native structure of ferroxidase II is required for the maintenance of i-s functional integrity.

Apoenzymes↗
PubMed1976

The serum ferroxidase system and the effect of estrogen on plasma iron.

Estrogen effects on plasma iron and ferroxidase activity in some mammals and domestic fowl are studied, to investigate a possible estrogen mechanism on iron through its action on the ferroxidase system. Although estrogen generally induces ceruloplasmin, iron mobilization, characterized by a rise in plasma iron, was evident only in rats and chickens. Gonadotrophin treatment confirmed these results. A decreasing affect on plasma iron was noted in rabbits and guinea-pigs, substantiated by some bibliographical data. Ferroxidase activity increased and a copper-dependent factor was evident in copper injected species. Iron mobilization, however, was produced only in rats and chickens. D-penicillamine treatment considerably lowered ferroxidase activity in rats and suppressed the estradiol increasing plasma iron effect. This response to the copper-chelating drug did not take place in the other species. This phenomenon could be explained by the presence of two copper-dependent ferroxidases (ferroxidase I or ceruloplasmin and ferroxidase II) in rat plasma, as recently published.

Animals↗
PubMed1992

Ferroxidase kinetics of horse spleen apoferritin.

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.

Animals↗
PubMed2025

Integrative spatial transcriptomic analysis pinpoints the role of the ferroxidase, TaMCO3, in wheat root tip iron mobilization.

Roots play a critical role in the sensing and absorption of essential minerals from the rhizosphere. Iron (Fe) deficiency, for example, triggers a well-known series of physiological and molecular responses within roots that facilitate uptake, which differs between monocots and dicots. In monocots, little is known about the molecular responses that occur within specific root development zones in response to iron deprivation, and how these differences result in overall nutrient uptake. Here, we conducted a transcriptome analysis of wheat root tips under Fe deficiency (-Fe) and performed a comparative transcriptome analysis with the previous datasets generated from the whole root. Gene ontology analysis of differentially expressed genes highlighted the significance of oxidoreductase activity and metal/ion transport in the root tip, which are critical for Fe mobilization. Interestingly, wheat, an allohexaploid species consisting of three different genomes (A, B, and D) displayed varying gene expression levels arising from the three genomes that contributed to similar molecular functions. Detailed analysis of oxidoreductase function at the root tip revealed multiple multicopper oxidase (MCO) proteins, such as Fe-responsive TaMCO3, that likely contribute to the overall ferroxidase activity. Further characterization of TaMCO3 shows that it complements the yeast FET3 mutant and rescues the -Fe sensitivity phenotype of Arabidopsis atmco3 mutants by enhancing vascular Fe loading. Transgenic wheat lines overexpressing TaMCO3 exhibited increased root Fe accumulation and improved tolerance to -Fe by augmenting the expression of Fe-mobilizing genes. Our findings highlight the role of spatially resolved gene expression in -Fe responses, suggesting strategies to reprogram cells for improved nutrient stress tolerance.

Triticum↗
PubMed1975

Intramolecular electron transport in human ferroxidase (caeruloplasmin).

The oxidation of reduced human ferroxidase by molecular O2 was studied in a stopped-flow spectrophotometer. It was shown that the two type 1 copper atoms behave differently in the absence of iron. The effect of iron on the kinetic parameters was investiagted. A working model for intramolecular electron transport in the enzyme is proposed.

Ceruloplasmin↗
PubMed1992

[Probucol inhibits tobacco smoke-induced decrease in plasma anti-elastase activity and ferroxidase activity in rats].

Elastolytic enzymes and active oxygen species derived from leukocytes and alveolar macrophages during exposure to tobacco smoke, together with active oxygen species directly derived from tobacco smoke, are thought to play a crucial role in the pathogenesis of pulmonary emphysema by inactivating alpha 1 protease inhibitor (alpha 1 PI), a novel anti-elastase. We studied the inhibitory effect of probucol, an oral hypocholesterolemic agent, on tobacco smoke-induced decrease in plasma anti-elastase activity (EIA) and ferroxidase activity (FA) in conscious venous catheter instrumented rats. Rats exposed to the smoke of 5 cigarettes (nicotine 11 mg, tar 115 mg) in a plastic chamber showed a prompt increase in plasma COHb to 17.9 +/- 2.7%, and a prompt decrease in plasma EIA by -17.9% (p less than 0.05) and FA by -14.8% (p less than 0.01), which lasted for 6 hours after exposure. Rats administered probucol (1% probucol in food) for 3 days showed normal cholesterol plasma levels, and rats administered probucol for 4 weeks showed hypocholesterolemic plasma levels. EIA and FA were not depressed after smoking, and lipid peroxide product (TBA reactive substance) in lung tissue (p less than 0.05) and serum (p less than 0.1) showed a smaller increase in association with a smaller decrease in the ratio of lung tissue GSH/GSSG (p less than 0.01) compared with control rats. These results indicate that probucol, via its antioxidant action rather than its cholesterol lowering effect, has a protective effect on lung exposed to tobacco smoke in terms of protease-antiprotease balance and oxidant-antioxidant balance.

Animals↗
PubMed1976

Reinvestigation of some physicochemical and chemical properties of human ceruloplasmin (ferroxidase).

The original molecular weight determinations and hydrodynamic data on ceruloplasmin have later been contradicted by crystallographic and other investigations. In order to arrive at the correct copper stoichiometry of the protein we have undertaken a careful reinvestigation of some aspects of the physical chemistry and chemistry of ceruloplasmin with particular attention directed towards molecular weight and copper content. Human ceruloplasmin form I (the major form) was isoalted from fresh normal or retroplacental serum by a procedure designed to avoid proteolysis. The molecular weight of the protein, determined by meniscus depletion sedimentation equilibrium, was found to be 134 000+/-3 000. The sedimentation coefficient (7.25 S) and diffusion coefficient (4.46 10(-7) cm2/s) are consistent with this molecular weight. The frictional ratio calculated from these data, 1.41, and the observed intrinsic viscosity of 4.5 ml/g indicate that ceruloplasmin has a slightly more extended shape than a typical globular protein. This might at least partly be ascribed to its carbohydrate moiety. The amino acid composition, carbohydrate composition, and copper content of ceruloplasmin were determined. The copper content of several preparations varied between 6.0 and 6.6 atoms per mol. The copper stoichiometry of ceruloplasmin is discussed.

Amino Acids↗
PubMed1976

Copper deficiency and erythrocuprein (2Cu, 2Zn-superoxide dismutase).

The activities of 2Cu,2Zn-superoxide dismutase, ferroxidase (ceruloplasmin), catalase and glutathione peroxidase were measured in the blood of rats during copper depletion. Two control groups of animals were used; one received the regular diet containing all essential components including copper and the other group was maintained on a diet, containing 1% the amount of copper in normal diet, copper being supplied as Cu(Leu)2 in the drinking water. Both groups showed no detectable differences, either in the copper content of blood or in the measured four enzymic activities. Excessive copper (injected intraperitoneally) caused only an insignificant rise in the enzymic activities (0-10%) compared to either control. After starting copper depletion ferroxidase activity decreases to 15% on the 15th day, while the 2Cu,2Zn-superoxide dismutase activity decreases to 40% on the 45th day. Ferroxidase activity shows rapid but transient changes immediately after perturbation in plasma copper levels. By contrast, the 2Cu,2Zn-superoxide dismutase activity more closely parallels the overall copper deficiency. Dietary repletion with copper raises the 2Cu,2Zn-superoxide dismutase activity to 94% and the ferroxidase activity to 80% of the control values within 36 h. Apart from the copper-dependent anemia catalase activity was decreased. However, 15 days after the start of the copper depletion catalase activity rises again and reaches the control value on the 40th day and a 30% stimulation was even seen on the 58th day. Upon copper repletion catalase activity reaches 166% of the control within 14 days. No copper-dependent differences of glutathione peroxidase activity were seen regardless whatever copper level was present in the rats.

Animals↗
PubMed1992

Evidence of H- and L-chains have co-operative roles in the iron-uptake mechanism of human ferritin.

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.

Apoferritins↗
PubMed1976

The biological role of ceruloplasmin and its oxidase activity.

Ceruloplasmin (ferroxidase) the blue Cu-protein of vertebrate plasma, possesses significant oxidase activity towards Fe(II) and numerous aromatic amines and phenols. Its ferroxidase activity has led to the discovery that it is a molecular link between copper and iron metabolism. Ceruloplasmin mobilizes iron into the plasma from iron storage cells in the liver. An additional role of Cp may be as a contributor to the regulation of the balance of biogenic amines through its oxidase action on the epinephrine and the hydroxyindole series. Ceruloplasmin also serves as a major copper transport vehicle, comparable to transferrin for iron. Evidence is presented that the copper atoms of Cp are a prerequisite for copper utilization in the biosynthesis of cytochrome oxidase. The ability of Cp to release copper at specific cellular sites is believed to be related to its broad substrate spectrum of biological reducing agents. Thus Cp is a serum protein with several important functions, all of which are directly related to its oxidase activity.

Animals↗
PubMedDate not supplied

Structure, function, and evolution of ferritins.

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.

Amino Acid Sequence↗
PubMed1975

Iron oxidation and transferrin formation by phosvitin.

The catalytic activity of phosvitin in Fe(II) oxidation and the addition of iron to transferrin were studied under various conditions. It was concluded that the Fe(II) oxidized by phosvitin would bind to apotransferrin, although an appreciable fraction of Fe(III) remained bound to phosvitin. Fe(III) also migrated from phosvitin to apotransferrin. This reaction was first-order with respect to Fe(III)-phosvitin concentration with a half-time (t1/2) of 10 min, and a first-order rate constant, k=0.069min-1, in 700 muM-phosphate buffer, pH 7.2, at 30 degrees C. The catalysis of the oxidation of Fe(III) by phosvitin was proportional to O2 concentration, and is quite different from the relative O2 independence of Fe(II) oxidation as catalysed by ferroxidase. A scheme for the mobilization and transfer of iron in the chicken, including the role of ferroxidase, phosyitin and transferrin, is presented.

Animals↗
PubMed1992

Iron-induced ascorbate oxidation in plasma as monitored by ascorbate free radical formation. No spin-trapping evidence for the hydroxyl radical in iron-overloaded plasma.

A study was made of the interaction of plasma ascorbate and ascorbate free radical (AFR) with exogenously added iron. The quantitative determination of AFR has the advantage that transient increases in ascorbate oxidation can be directly monitored by e.p.r. spectroscopy. An AFR signal was found in the plasma of all donors and was unaffected by superoxide dismutase, catalase and the strong iron chelator deferoxamine. These findings and the rapid decrease in AFR under a nitrogen atmosphere suggest that plasma AFR is probably a result of air auto-oxidation. Iron loading of plasma did not affect the intensity of the AFR signal until the iron concentration approached or exceeded the plasma latent iron-binding capacity. In iron-overloaded plasma, the intensity of the AFR signal increased to about 10 times the normal level before decreasing rapidly to undetectable levels after 15-20 min. Determination of plasma ascorbate showed that the disappearance of AFR was due to a complete loss of the vitamin. When 50 microM-ascorbate was loaded with iron in iso-osmotic phosphate buffer there was an increase in the AFR signal, independent of the iron concentration, which was stable at least for 15 min. Thus the rate of ascorbate loss in the iso-osmotic phosphate buffer was considerably lower than in iron-overloaded plasma. The addition of different iron chelators produced comparable effects on the intensity of the AFR signal in both iron-overloaded plasma and ascorbate solution. These results suggest that the characteristic behaviour of plasma AFR after iron loading is due to its specific iron-binding capacity and to plasma ferroxidase activity. The ferroxidase activity of plasma is important to promote the transfer of Fe2+ into transferrin without a transient ascorbate oxidation. Spin-trapping studies with 5,5-dimethyl-1-pyrroline N-oxide and N-t-butyl-alpha-phenylnitrone revealed that iron-overloaded plasma was unable to produce spin-trap adducts even in the presence of 50-300 microM-hydrogen peroxide or 100 microM-azide. Evidence of OH. radical formation was obtained only after the addition of EDTA. Therefore, iron-overloaded plasma itself does not produce a Fenton reaction and, if ascorbate does indeed have a free-radical-mediated pro-oxidant role, it is not detectable in plasma by spin-trapping experiments.

Ascorbic Acid↗
PubMed1991

Plasma ascorbate levels and inhibition of the antioxidant activity of caeruloplasmin.

1. The copper-containing protein caeruloplasmin has several oxidase activities. 2. Its ability to catalyse the oxidation of ferrous ions to the ferric state (ferroxidase activity) makes it an important antioxidant in vivo. 3. Recent reports have suggested that oral supplementation with vitamin C can inhibit the oxidase activities of caeruloplasmin. 4. As expected, damage to DNA and membrane lipids was stimulated by mixtures of iron salt and ascorbate, and this damage could be inhibited by caeruloplasmin provided the molar ratio of ascorbate to caeruloplasmin was kept sufficiently low. 5. When the molar ratio of ascorbate to caeruloplasmin was greater than 200 substantial loss of ferroxidase antioxidant activity occurred. 6. It is unlikely, however, that oral supplementation with vitamin C can raise plasma levels sufficiently to inhibit caeruloplasmin activity in vivo.

Animals↗
PubMed1976

Biochemical and pathological changes in tissues of Friesian cattle during the experimental induction of copper deficiency.

1. Copper deficiency was induced in five Friesian cattle offered a semi-synthetic diet containing less than 1 mgCu/kg. Changes in blood and liver Cu contents and in the Cu-containing enzymes, ferroxidase I (caeruloplasmin; EC 1.16.3.1) and monoamine oxidase (EC 1.4.3.4) of plasma and cytochrome oxidase (EC 1.9.3.1) of liver and skeletal muscle were monitored during Cu depletion. 2. Rapid decreases in blood and liver Cu and plasma ferroxidase I activity were found at least 80 d before the first appearance of overt clinical signs of deficiency. Plasma monoamine oxidase and liver cytochrome oxidase activities decreased less rapidly and thus may provide useful indices of chronic Cu depletion.

Animals↗