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At least 865 records · Page 48Linked to original sources
PubMed2005

The copper chelator methanobactin from Methylosinus trichosporium OB3b binds copper(I).

The oxidation state of copper bound to methanobactin, a small siderophore-like molecule from the methanotroph Methylosinus trichosporium OB3b, was investigated. Purified methanobactin loaded with Cu(II) exhibits a weak EPR signal probably due to adventitious Cu(II). The EPR signal intensity increases significantly upon addition of the strong oxidant nitric acid. Features of the X-ray absorption near edge spectrum, including a 1s --> 4p transition at 8985 eV, further indicate the presence of Cu(I). EXAFS data were best fit using a multiple scattering model generated from previously reported crystallographic parameters. These results establish definitively that M. trichosporium OB3b methanobactin binds Cu(I) and suggest that methanobactin itself reduces Cu(II) to Cu(I).

Absorptiometry, Photon↗
PubMed2003

Zinc and copper complexes of prodigiosin: implications for copper-mediated double-strand DNA cleavage.

[reaction: see text] Zinc(II) and copper(II) complexes of prodigiosin (1) have been characterized. All N-atoms of 1 bind Cu(II) to generate 5: the complex exhibits regiospecific oxidation of the C-pyrrole. In contrast, coordination by Zn(II) to 1 produces Zn(1)(2) (8), a 4-coordinate tetrahedral complex. The influence of these binding geometries on Cu-mediated double-strand (ds) DNA cleavage by 1 is discussed.

Anti-Bacterial Agents↗
PubMed2001

No effect of copper supplementation on biochemical markers of bone metabolism in healthy young adult females despite apparently improved copper status.

OBJECTIVE: To investigate the effects of increasing Cu intakes, above the usual dietary intake, on biomarkers of bone metabolism in healthy young adult females (aged 21-28 y) over a 4 week period. DESIGN: A double-blind, placebo-controlled randomised repeat crossover Cu supplementation trial. SETTING: The study was conducted at the Royal Veterinary and Agricultural University (RVAU), Copenhagen, Denmark. SUBJECTS: Sixteen healthy young adult females aged 20-28 y were recruited from among students at the RVAU. INTERVENTION: During the 4 week intervention periods in this randomised, crossover trial (3x4 weeks with a minimum 3 week wash-out period), each subject received, in addition to their usual diet, either 3 or 6 mg elemental Cu/day as CuSO4 or a matching placebo. On the last 3 days of each dietary period 24 h urines were collected. In addition, blood was collected on the last day of each dietary period. RESULTS: Serum Cu and erythrocyte superoxide dismutase (but not caeruloplasmin protein concentration or activity (putative indices of Cu status)) were significantly increased (P<0.05) after daily Cu supplementation with 3 and 6 mg/day for 4 weeks. Serum osteocalcin (biomarker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline (Pyr)/Cr or deoxypyridinoline (Dpyr)/Cr excretion, or daily urinary Pyr or Dpyr excretion (biomarkers of bone resorption) were unaffected by Cu supplementation. CONCLUSION: Copper supplementation of the usual diet in healthy young adult females, while apparently improving Cu status, had no effect on biochemical markers of bone formation or bone resorption over 4 week periods. SPONSORSHIP: Funding from the European Commission.

Adult↗
PubMed2001

Catalytic and spectroscopic analysis of blue copper-containing nitrite reductase mutants altered in the environment of the type 2 copper centre: implications for substrate interaction.

The blue dissimilatory nitrite reductase (NiR) from Alcaligenes xylosoxidans is a trimer containing two types of Cu centre, three type 1 electron transfer centres and three type 2 centres. The latter have been implicated in the binding and reduction of nitrite. The Cu ion of the type 2 centre of the oxidized enzyme is ligated by three His residues, and additionally has a co-ordinated water molecule that is also hydrogen-bonded to the carboxyl of Asp(92) [Dodd, Van Beeumen, Eady and Hasnain (1998), J. Mol. Biol. 282, 369-382]. Two mutations of this residue have been made, one to a glutamic acid residue and a second to an asparagine residue; the effects of both mutations on the spectroscopic and catalytic properties of the enzyme have been analysed. EPR spectroscopy revealed that both mutants retained intact type 1 Cu centres with g( parallel)=2.12 (A( parallel)=0 mT) and g( perpendicular)=2.30 (A( perpendicular)=6.4 mT), which was consistent with their blue colour, but differed in their activities and in the spectroscopic properties of the type 2 centres. The D92E mutant had an altered geometry of its type 2 centre such that nitrite was no longer capable of binding to elicit changes in the EPR parameters of this centre. Accordingly, this mutation resulted in a form of NiR that had very low enzyme activity with the artificial electron donors reduced Methyl Viologen and sodium dithionite. As isolated, the EPR spectrum of the Asp(92)-->Asn (D92N) mutant showed no characteristic type 2 hyperfine lines. However, oxidation with iridium hexachloride partly restored a type 2 EPR signal, suggesting that type 2 copper is present in the enzyme but in a reduced, EPR-silent form. Like the Asp(92)-->Glu mutant, D92N had very low enzyme activities with either Methyl Viologen or dithionite. Remarkably, when the physiological electron donor reduced azurin I was used, both mutant proteins exhibited restoration of enzyme activity. The degree of restoration differed for the two mutants, with the D92N derivative exhibiting approx. 60% of the activity seen for the wild-type NiR. These findings suggest that on formation of an electron transfer complex with azurin, a conformational change in NiR occurs that returns the catalytic Cu centre to a functionally active state capable of binding and reducing nitrite.

Alcaligenes↗
PubMed1978

The binding of copper ions to copper-free bovine superoxide dismutase. Kinetic aspects.

The kinetics of reconstitution of bovine superoxide dismutase from Cu2+ and the copper-free enzyme have been studied by activity, u.v.-absorption, electron-paramagnetic-resonance and pulsed-nuclear-magnetic-resonance measurements. The process appears to be first-order up to 80% completion in most conditions, and is pH-dependent, with an apparent pK of 6.5. U.v.-absorption and solvent proton relaxation rate measurements show that fast binding of Cu2+ occurs, and the initial ligands are likely to be, at least in part, those of the native active site. The recovery of the native activity and spectroscopic properties is a slow process with activation energies of 92 kJ/mol at pH 5.3 and 8.4kJ/mol at pH 8.1 and can be described as a rearrangement of the site around the bound metal. The rate of this process is lower in partially recombined protein samples, probably because of intersubunit interactions.

Acetates↗
PubMed2001

Effects of D-penicillamine on urinary copper excretion in high-copper supplemented sheep.

The effects of a single oral application of D-penicillamine (DPA, mean dosage 28 mg/kg body weight) on urinary copper (Cu) excretion and general renal function in six high-Cu supplemented sheep (Cu intake of 3.7 mg/day per kg body weight for 84 days) and four controls (Cu intake of 0.16 mg/day per kg body weight) were investigated to quantify induced cupruresis and the therapeutic effect of DPA as a decoppering agent. Changes in liver Cu concentration were examined before and after DPA treatment by liver biopsies. The influence of DPA treatment on general renal function was low. A 10-fold increase in renal Cu excretion was induced in both groups of sheep. Maximal Cu excretion was observed 4 h after DPA treatment, with mean values of 280 pmol/min per kg body weight in the high Cu group and 145 pmol/min per kg body weight in the controls. In the high Cu sheep, urinary Cu excretion within 24 h after DPA application was equivalent to only 0.42 +/- 0.26% of liver Cu content (mean concentration 347 +/- 124 mg/kg wet weight). Moreover, no effect of DPA on liver Cu concentration was evident. These findings demonstrate that a single application of DPA is not effective in inducing sufficient Cu loss from the bodies of Cu-loaded sheep.

Animals↗
PubMed2004

Direct probing of copper active site and free radical formed during bicarbonate-dependent peroxidase activity of bovine and human copper, zinc-superoxide dismutases. Low-temperature electron paramagnetic resonance and electron nuclear double resonance studies.

Using X-band electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) spectroscopy at liquid helium temperatures, the Cu(II) coordination geometry at the active site of bovine and human copper,zinc-superoxide dismutases (bSOD1 and hSOD1) treated with H(2)O(2) and bicarbonate (HCO(3)(-)) was examined. The time course EPR of wild type human SOD1 (WT hSOD1), W32F hSOD1 mutant (tryptophan 32 substituted with phenylalanine), and bSOD1 treated with H(2)O(2) and HCO(3)(-) shows an initial reduction of active site Cu(II) to Cu(I) followed by its oxidation back to Cu(II) in the presence of H(2)O(2). However, HCO(3)(-) induced a Trp-32-derived radical from WT hSOD1 but not from bSOD1. The mutation of Trp-32 by phenylalanine totally eliminated the Trp-32 radical signal generated from W32F hSOD1 treated with HCO(3)(-) and H(2)O(2). Further characterization of the free radical was performed by UV irradiation of WT hSOD1 and bSOD1 that generated tryptophanyl and tyrosyl radicals. Both proton ((1)H) and nitrogen ((14)N) ENDOR studies of bSOD1 and hSOD1 in the presence of H(2)O(2) revealed a change in the geometry of His-46 (or His-44) and His-48 (or His-46) coordinated to Cu(II) at the active site of WT hSOD1 and bSOD1, respectively. However, in the presence of HCO(3)(-) and H(2)O(2), both (1)H and (14)N ENDOR spectra were almost identical to those derived from native bSOD1. We conclude that HCO(3)(-)-derived oxidant does not alter significantly the Cu(II) active site geometry and histidine coordination to Cu(II) in SOD1 as does H(2)O(2) alone; however, the oxidant derived from HCO(3)(-) (i.e. carbonate anion radical) reacts with surface-associated Trp-32 in hSOD1 to form the corresponding radical.

Animals↗
PubMed1977

The effect of dietary copper sulphate on laying performance, nutrient intake and tissue copper and iron levels of the mature, laying, domestic fowl.

1. A cereal-based diet containing 16 mg copper/kg was fed ad lib. to a group of laying hens for 35 d. Five other groups were given this control diet to which was added 120, 240, 480, and 1920 mg Cu/kg (as copper sulphate). 2. Records were kept of daily food intake, water intake and egg production. 3. After 35 d the hens were slaughtered and blood haemoglobin, packed cell volume, Cu and aspartate aminotransferase (EC 2.6.1.1) levels assayed. Liver, oviduct, kidney and breast muscle Cu and iron concentrations were measured. 4. Food and water intakes were depressed by the two highest levels of dietary Cu and water intake was increased by the diet with 240 mg added Cu/kg. Both food and water intake showed a quadratic relationship with the level of added dietary Cu. 5. Body-weight loss was increased by the addition of Cu and showed a significant linear relationship with the concentration of added Cu in the diet. Liver and oviduct weights were depressed at the two highest levels of Cu addition. 6. Liver and oviduct Cu and Fe concentrations were significantly increased by high dietary Cu and mean total liver and kidney Cu and Fe showed an increase although for the liver this was not statistically significant.

Animal Nutritional Physiological Phenomena↗
PubMed1989

Copper absorption and retention in young men at three levels of dietary copper by use of the stable isotope 65Cu.

Eleven young men were confined to a metabolic research unit for 90 d to determine the effect of the level of dietary copper on absorption and retention. Cu absorption was determined by feeding the stable isotope 65Cu. Absorption and retention averaged 36.3 +/- 1.3% and 0.17 mg/d, respectively, with an adequate-Cu diet (1.68 mg/d). Absorption averaged 55.6 +/- 0.9% and retention averaged -0.316 mg/d for 6 d and 0.093 mg/d for the next 36 d of a low-Cu diet (0.785 mg/d). Absorption averaged 12.4 +/- 0.9% with a high-Cu diet (7.53 mg/d) and retention was strongly positive at first, decreasing linearly with time. The study demonstrated that Cu absorption is strongly dependent on dietary Cu level and that Cu balance can be achieved by most young men from a diet of 0.8 mg Cu/d. These results suggest that current dietary Cu recommendations may be higher than necessary. The apparent regulation of Cu absorption and endogenous losses would tend to protect humans from Cu deficiency and toxicity.

Adult↗
PubMed1989

Copper supplementation: failure to increase plasma copper and ceruloplasmin concentrations in healthy infants.

Plasma copper and ceruloplasmin concentrations at ages 0, 2, 4, 6, 9, and 12 mo were longitudinally evaluated in our Finnish nutritional survey of 200 infants. The infants, who were weaned by age 3.5 mo, were randomly assigned to receive either a liquid cow-milk-based formula containing 1.3 mumol Cu/L (n = 16) or the same formula supplemented with 7.8 mumol Cu/L as Cu sulfate (n = 16). They were compared with exclusively breast-fed infants. Plasma Cu and ceruloplasmin concentrations increased steadily and similarly in all three groups from 4.6 +/- 0.2 mumol/L (means +/- SEM) and 0.9 +/- 0.1 mumol/L, respectively, in umbilical samples to 19.7 +/- 0.3 mumol/L and 3.2 +/- 0.1 mumol/L, respectively, at age 12 mo. Our results indicate that concentrations of plasma Cu and ceruloplasmin in healthy full-term infants are resistant to dietary supplementation.

Age Factors↗
PubMed1990

Copper status and function of neutrophils are reversibly depressed in marginally and severely copper-deficient rats.

Weaned male rats were pair-fed diets containing either adequate (7 mg/kg diet; +Cu) or deficient (0.7 mg/kg diet; -Cu) levels of copper for 5 wk. Cellular Cu concentration, activity of Cu,Zn superoxide dismutase (Cu,Zn-SOD), generation of superoxide anion (O2-) in response to opsonized zymosan and phorbol myristate acetate, and candidacidal activity in elicited neutrophils were all significantly decreased by dietary Cu deficiency. Furthermore, survivability of Candida albicans injected into the peritoneal cavity of Cu-deficient rats was greater than in controls. Phagocytic activity of neutrophils was independent of cellular Cu status. To determine whether the impaired function of neutrophils was also characteristic of marginal Cu deficiency, weaned rats were fed diets containing either 0.6, 1.1, 2.0, 2.7 or 6.7 (control) mg Cu/kg for 5 wk. The activity of Cu,Zn-SOD, phorbol myristate acetate-induced production of O2-, and candidacidal activity were significantly lower in neutrophils from rats fed diets with less than or equal to 2.7 mg Cu/kg compared to control cells. In contrast, decreased tissue Cu and the activity of erythrocyte Cu,Zn-SOD were observed only when dietary Cu was less than or equal to 2.0 mg/kg. Reduced SOD activity, respiratory burst and candidacidal activity of neutrophils were evident as soon as 1 wk after initiating the dietary treatment. Feeding +Cu diet to Cu-deficient rats for 1 wk restored Cu status and function of neutrophils to control levels. These results show that neutrophil function is reversibly impaired by marginal and severe Cu deficiency and suggest that the Cu status and function of these cells may provide a sensitive indicator for assessment of Cu status.

Animals↗
PubMed1993

Copper repletion restores the number and function of CD4 cells in copper-deficient rats.

Dietary copper deficiency decreases the number of splenic CD4 cells and mitogen-induced generation of interleukin-2 activity and DNA synthesis in cultures of splenic mononuclear cells. To determine the reversibility of these defects, Cu-deficient rats were fed a Cu-adequate diet for either 4, 7 or 11 d before preparation of cell cultures. Serum and hepatic concentrations of Cu attained 87 and 75%, respectively, of the control level after 4 d of dietary repletion. In contrast, interleukin-2 activity and [3H]thymidine incorporation in splenic cell cultures treated with T-cell mitogens were significantly greater than in cultures from Cu-deficient rats after 7, but not 4, d of dietary Cu repletion. The number of splenic CD4 cells was also greater after 7 d of dietary supplementation with Cu. Changes in the relative percentage and function of T-helper cells were highly correlated with one another and with hepatic Cu concentration. These observations indicate that an inadequate supply of dietary Cu reversibly suppresses the maturation and function of splenic T-helper cells.

Animals↗
PubMed1994

Pool size and concentration of plasma cholesterol are increased and tissue copper levels are reduced during early stages of copper deficiency in rats.

The progressive development of hypercholesterolemia, enlargement of plasma cholesterol pool size, and alteration in tissue mineral concentrations were determined during the early stages of copper deficiency. Fifty-four weanling male Sprague-Dawley rats were assigned to three dietary Cu treatments: deficient (0.6 micrograms Cu/g diet), marginal (1.6 micrograms Cu/g diet) and adequate (6.6 micrograms Cu/g diet). Six rats from each treatment were killed after 3, 5 and 7 wk of dietary treatment. After only 3 wk of treatment, significantly lower hematocrits and liver Cu concentrations, as well as enlargements of plasma volume, plasma pool size of cholesterol and triacylglycerols and relative heart weight, were evident in rats fed the Cu-deficient and Cu-marginal diets relative to those fed the Cu-adequate diet. In general, these alterations were more pronounced in rats fed the Cu-deficient diet than in rats fed the Cu-marginal diet. Thereafter, the hematocrits and plasma volumes remained relatively constant, but the liver Cu concentration progressively decreased in rats in all treatments throughout the study. In contrast, the enlargements in plasma pool size of cholesterol and triacylglycerols relative to Cu-adequate rats were greater at the end of the study for the Cu-marginal and Cu-deficient rats. Most importantly, in the Cu-marginal rats, significantly greater plasma cholesterol and triacylglycerol pool sizes were detected earlier than were differences in concentrations. Thus, the present study established plasma cholesterol and triacylglycerol pool sizes as superior indices for the early detection of alterations in lipid metabolism in Cu deficiency.

Administration, Oral↗
PubMed1999

Dietary copper primarily affects antioxidant capacity and dietary iron mainly affects iron status in a surface response study of female rats fed varying concentrations of iron, zinc and copper.

This study was designed to examine the interactions among dietary iron (Fe), copper (Cu), and zinc (Zn) and their effects on Fe status and oxidative stress in female rats. In a three-factor central composite response surface design, rats were assigned to 15 groups and fed modified AIN-93G basal diets with varying amounts of Fe and Zn (7.0, 15.5, 45.8, 135.6, or 300 micrograms/g diet) and Cu (0.5, 1.1, 3.2, 9.2, or 20 micrograms/g diet) for 6 wk. Variations in hemoglobin, hematocrit, and serum ferritin were mainly related to dietary Fe. Liver nonheme Fe was directly affected by dietary Fe and was slightly attenuated by interactions between Cu and Zn, and Zn and Fe. Serum ceruloplasmin activity was primarily determined by an interaction between Cu and Zn with substantial moderation by the quadratic effect of dietary Cu. Liver and heart total superoxide dismutase (SOD) and Cu/Zn SOD activities were directly affected by dietary Cu. Dietary Fe was the only significant, yet weak, predictor of liver thiobarbituric acid reactive substances (TBARS) and vitamin E content and serum triacylglycerols. Variability in serum Cu was mostly determined by the interaction between Cu and Fe, with modification from the quadratic effect of dietary Cu. Serum Zn varied with dietary Zn with a small negative influence from the interaction between Cu and Fe. In summary, Fe status was minimally influenced by dietary Zn or Cu, and Fe intakes 10-fold greater than required did not induce overt oxidative stress in female rats. In addition, measures of antioxidant capacity were primarily influenced by dietary Cu and were optimal at moderate intakes of this micronutrient.

Animals↗
PubMed2003

Inadequate copper intake reduces serum insulin-like growth factor-I and bone strength in growing rats fed graded amounts of copper and zinc.

This study examined the effects of graded intakes of zinc (Zn) and copper (Cu) on serum insulin-like growth-factor-I (IGF-I) concentration and bone quality in growing rats. Using a 3 x 4 factorial design, weanling male Sprague-Dawley rats were randomly assigned to 12 groups (n = 7 per group) and were fed one of nine modified AIN-93G basal diets with varying amounts of Cu (0.3, 3 and 10 micro g/g) and Zn (5, 15 and 45 micro g/g) for 6 wk. A group of rats was pair-fed to each low Zn group. Although dietary Zn mainly influenced body weights (P < 0.0001), dietary Cu was the main determinant of most of the variables related to bone quality. Low Cu intake reduced serum IGF-I and femur breaking force and ultimate stress (by 27, 14 and 7%, respectively; P < 0.05) and increased bone IGF-I concentration (by 62%; P < 0.0001). Low Cu intake also increased femur nitrogen, hydroxyproline, hexosamine and calcium (Ca) concentrations of long bones (P < 0.05). Lumbar vertebrae dry weight and density were the lowest in the rats fed the low Cu diets (P < 0.001) and were higher in the rats fed high amounts of both Cu and Zn (P < 0.01). In summary, growing rats fed low and marginal Cu had lower serum IGF-I than those fed high dietary Cu. Bone strength was also reduced with low dietary Cu, despite compensatory changes in the bone matrix. In the presence of graded intakes of Cu, the effects of low dietary Zn were more pronounced on the spinal bones than the long bones.

Analysis of Variance↗
PubMed1985

Specific cleavages of DNA by ascorbate in the presence of copper ion or copper chelates.

The DNA-cleavage specificity of ascorbate in the presence of copper ion is analyzed with end-labeled pBR322 DNA fragments. The nonenzymatic reaction of Cu(II)/ascorbate and DNA shows certain degrees of cleavage preference toward purine-containing short segments in the labeled DNA under mild conditions (at 0 degrees C and 10 min). The segments of pyrimidine clusters are least susceptible to cleavage. The DNA scission cannot be detected in the absence of metal ions, and is greatly diminished in the presence of EDTA and metal-chelating peptide. It is more specific than the nuclease-like scission activity induced by cuprous-phenanthroline complex. This scission activity in relation to the antiviral and antitumor activities of vitamin C reported in the literature deserves a crucial consideration.

Ascorbic Acid↗