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PubMed1984

Effects of zinc and copper content of formulas on growth and on the concentration of zinc and copper in serum and hair.

We studied the effect of dietary zinc (Zn) and copper (Cu) on the levels of these elements in serum (at 1, 3, and 5 months of age) and in hair (at 5 months of age) of breast- and formula-fed infants. Three different formulas were used: (a) Commercially available standard infant formula containing 1.0 mg/L of Zn and 30 micrograms/L of Cu; (b) Zn supplemented formula, containing 3.2 mg/L of Zn and 30 micrograms/L of Cu; and (c) Zn- and Cu-supplemented formula, containing 3.2 mg/L of Zn and 400 micrograms/L of Cu. The median Zn content of breast milk was 4.8 mg/L at 1 week, 2.9 mg/L at 1 month, 1.1 mg/L at 3 months and 1.1 mg/L at 5 months. Breast milk Cu content was 510 micrograms/L at 1 week, 440 micrograms/L at 1 month, 270 micrograms/L at 3 months, and 200 micrograms/L at 5 months after delivery. All infants were healthy and full term, and weight and length velocities were similar in each of the four groups studied. Serum Zn levels were significantly higher both in the infants fed the Zn-supplemented formula and those fed the Zn-and-Cu-supplemented formula compared with the other two groups of infants at 3 and 5 months of age. Zn levels in hair were significantly elevated (invariably greater than 80 micrograms/g) only in infants fed Zn-supplemented formula.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1991

Copper metallothionein in patients with hepatic copper overload.

We studied the Cu-MT present in the hepatic cytosol obtained from 7 patients suffering from conditions associated with hepatic Cu overload (Wilson's disease, biliary atresia, familial cholestatic cirrhosis). Since chromatographic methods appropriate for the isolation of Zn- and Cd-MT were unsuitable for Cu-MT, we developed an indirect procedure for the estimation and resolution of the latter. This procedure involved the preparation of apo-MT and its reconstitution to holo-MT with Zn or Cd. Three predominant isoforms of MT were present in all specimens. Our results indicate that at most 36 +/- 5% of the Cu present in the 10 kDa fraction of cytosol is bound to MT in the liver of patients with hepatic copper overload.

Adolescent↗
PubMed1976

Anion complexes of Cu(II) and Co(II) bovine carbonic anhydrase as models for the copper site of blue copper proteins.

1. The presence of two intense transitions in the optical absorption spectrum of the sulfide and 2-mercaptoethanol complexes of Cu(II) and Co(II)-substituted bovine carbonic anhydrase suggest that charge-transfer interactions between sulfur and an acceptor group of the protein play an important role in the stabilization of these complexes. 2. The spectra of Co(II) bovine carbonic anhydrase sulfides are very similar to the spectrum of Co(II) stellacyanin whilst the spectra of the corresponding Cu(II) enzymes are considerably different. A possible explanation is that Cu(II) is pentacoordinate in native stellacyanin unlike Cu(II) bovine carbonic anhydrase sulfides and Co(II) enzymes. Tetrahedral Co(II) stellacyanin is proposed as a model of the reduced copper site.

Animals↗
PubMed1995

Histochemical localization of copper in various organs of brindled mice after copper therapy.

Copper (Cu) distribution in various organs of brindled mice (BM), an animal model of Menkes disease, was studied histochemically and by atomic-absorption-spectrophotometry 7 months after Cu injections. The results were compared with those of untreated BM. In the treated BM brain, a diffuse reduction in Cu-related staining of neurons and astroglia was still evident, though it had improved to some extent. The reduction was noticeable in the thalamus, brain stem and cerebellum, although intensely stained capillaries were noted occasionally in the retrosplenial and mediobasal temporal areas, including the hippocampus. In the treated BM liver, near normalization of Cu distribution was observed. In the treated BM intestine, the main localization of Cu accumulation was in histiocytes/macrophages in the lamina propria, while in the untreated BM it was in the absorptive and secretory epithelial cells. In the treated BM kidney, there was no clear improvement in Cu distribution. These histochemical results were consistent with the data obtained by the spectrophotometric assay. Electron microscopic histochemistry of affected renal tubular epithelial cells revealed numerous silver grains, which represent Cu++ localization, distributed only within the cytoplasm outside organella and nucleus. This suggests impaired intracellular Cu transport from cytosol to organella, which in the kidney is refractory to the Cu therapy adopted.

Animals↗
PubMed1983

Congenital copper deficiency: copper therapy and dopamine-beta-hydroxylase activity in the mottled (brindled) mouse.

The mottled (Mo) mouse is an animal model of the human congenital copper (Cu) deficiency disorder, Menkes' kinky hair syndrome. Intraperitoneal Cu chloride injections have been shown to produce clinical and morphological improvements in this mutant mouse. Cu injections (10 micrograms/g) on postnatal days 7 and 10 are shown to increase endogenous activity of the Cu-dependent enzyme dopamine-beta-hydroxylase in the brains of Mo mice. The present study provides insight into the long-term neurochemical changes resulting from a possible treatment regimen for Menkes' kinky hair syndrome.

Age Factors↗
PubMed1984

Solubility of copper and zinc containing proteins before and after 2-mercaptoethanol treatment of liver samples from normal and from chronically copper poisoned sheep.

The distribution between cytosol and pellet of Cu- and Zn-containing proteins was studied in livers from normal sheep and sheep with chronic copper poisoning (CCP). It was found that the relative amount of soluble Cu- and Zn-containing proteins was lower in liver homogenates from CCP sheep than in homogenates from normal sheep. Treatment of homogenate from the livers of 2-mercaptoethanol (ME) increased the solubility of Cu- and Zn-containing proteins, especially in CCP sheep. Oxidation of the liver homogenates from normal sheep with air oxygen gave a decrease in the relative amount of soluble CU-containing proteins and an increase in Zn-containing proteins present in the cytosol. It is proposed that oxidation in vivo of Cu and/or the metal-binding protein causes the observed decrease in soluble CU- and Zn-containing proteins seen in CCP sheep.

Animals↗
PubMed2005

Phenomenon of hepatic overload of copper in Mugil cephalus: role of metallothionein and patterns of copper cellular distribution.

In this work we describe a phenomenon of accumulation of copper (Cu) in livers of a teleost fish commonly known as mullet, Mugil cephalus. High levels of Cu, up to 1936 microg/g wet weight were found. The high Cu levels seem not to be associated with environmental Cu contamination, since the fish were collected from widely separated regions with low Cu concentrations. Other fish species sharing the same environment did not show high levels of Cu. The accumulation of Cu in mullet was seen in liver and most of the hepatic Cu was located in the non-cytosolic fraction. The intrahepatic distribution of Cu in mullet seems to depend on the total Cu content in the liver; as the total liver burden of Cu rose, Cu was increasingly recovered from the non-cytosolic fraction. Metallothionein in hepatic cytosols from mullet contained the most Cu. However, the Cu concentration not bound to metallothionein rose when total cytosolic Cu increased; which show that metallothionein, particularly at higher Cu levels, is not the major hepatic Cu-binding protein in cytosols of mullet. This report shows mullet as a very useful model to study the accumulation of Cu in the liver, which may lead to a better understanding of cellular mechanisms which control Cu homeostasis.

Anguilla↗
PubMed2005

Repletion of copper-deficient rats with dietary copper restores duodenal hephaestin protein and iron absorption.

Copper (Cu) deficiency in rats reduces the relative concentration of duodenal hephaestin (Hp), reduces iron (Fe) absorption, and causes anemia. An experiment was conducted to determine whether these effects could be reversed by dietary Cu repletion. Five groups of eight weanling male rats each were used. Group 1 was fed a Cu-adequate diet (5.0 mg Cu/kg; CuA) and Group 2 was fed a Cu-deficient diet (0.25 mg Cu/kg; CuD) for 28 days. The rats were fed 1.0 g each of their respective diets labeled with 59Fe (37 kBq/g), and the amount of label retained was measured one week later by whole-body-counting (WBC). Group 3 was fed a CuA diet and Groups 4 and 5 were fed a CuD diet for 28 days. Group 5 was then fed the CuA diet for another week while Groups 3 and 4 continued on their previous regimens. Rats in Groups 3, 4, and 5 were fed 1.0 g of diet labeled with 59Fe, and the amount of label retained was measured by WBC one week later. Rats were killed and duodenal enterocytes isolated for Hp protein analysis, whole blood was analyzed for hematological parameters, and various organs for 59Fe content. CuD rats absorbed less (P<0.05) Fe than CuA rats, the relative amount of duodenal Hp was less (P<0.05) in CuD rats, and the CuD rats developed anemia. After the CuD rats had been repleted with Cu for one week, Fe retention rose to values even higher (P<0.05) than those in CuA rats. After two weeks, the relative amount of duodenal Hp was higher (P<0.05) than normal, and most signs of anemia were reversed. Liver 59Fe was elevated in CuD rats, but was restored to normal upon Cu repletion. These findings suggest a strong association between duodenal Hp abundance and Fe absorption in the CuD rat, and that reduced Fe absorption is an important factor in the cause of anemia.

Animals↗
PubMed2000

Mechanisms of gastrointestinal copper absorption in the African walking catfish: copper dose-effects and a novel anion-dependent pathway in the intestine.

In mammals, copper (Cu) absorption occurs mostly in the small intestine, and some of the Cu transporters involved in its uptake have been characterised. In fish, however, the regions of the gut involved in Cu absorption and the membrane transport mechanisms responsible for gastrointestinal Cu uptake are unknown. Everted gut sacs and isolated perfused intestine of Clarias gariepinus were used to explore Cu absorption (at 22 degrees C). Gut sacs exposed to 100 micromol l(-1) mucosal solution Cu ([Cu](m)) showed that Cu was mostly (70 %) absorbed in the middle and hind intestine. Most of the accumulated Cu was located in the mucosa. In perfused intestines, cumulative Cu absorption from the mucosal solution to the serosal perfusate was greatest at 10 micromol l(-1) [Cu](m) and decreased at higher values of [Cu](m), while tissue accumulation of Cu showed a dose-dependent elevation. Absorption efficiency therefore declined with increasing Cu dose, and basolateral transport was the limiting factor in Cu uptake. Serosal applications of the P-type ATPase inhibitor vanadate (100 micromol l(-1)) or the anion transport inhibitor DIDS (100 micromol l(-1)) caused threefold increases in net Cu uptake (at [Cu](m)=10 micromol l(-1)). The vanadate effect was explained by a reduction in transepithelial potential rather than inhibition of Cu-ATPase, but the DIDS effect was not. Transepithelial potential, water transport and tissue [Cu] were not affected by DIDS, but tissue [K(+)] was elevated. Removal of Cl(-) simultaneously from both the mucosal and serosal solutions caused a 10-fold reduction in the rate of Cu uptake, while removal of Cl(-) from the mucosal solution only completely abolished Cu absorption to the serosal perfusate. Transepithelial potential effects are discussed. We conclude that Cu absorption occurs mostly in the intestine and is normally driven by a basolateral Cu/anion symport that prefers Cl(-).

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2002

Copper metabolism in actively growing rainbow trout (Oncorhynchus mykiss): interactions between dietary and waterborne copper uptake.

Juvenile rainbow trout Oncorhynchus mykiss were exposed to diets with low (12.6 nmol g(-1)), normal (50.4 nmol g(-1)) or elevated (4437.5 nmol g(-1)) Cu concentrations in combination with either low (5.8 nmol l(-1)) or normal (48.5 nmol l(-1)) waterborne Cu levels over a 50-day period, during which body mass increased up to fivefold. A nutritional requirement for Cu was demonstrated based on growth response and whole body and tissue Cu status. Simultaneous low Cu levels in both the water and the diet depressed growth by 31 % over 7 weeks. There were reductions in both specific growth rate (SGR, 1.95 versus 2.55 % day(-1)) and food conversion efficiency (FCE, 53-59 % versus 75-80 %) over weeks 0-4, but these effects disappeared in weeks 4-7. Elevated concentrations of dietary Cu did not affect SGR or FCE. Low levels of dietary and waterborne Cu decreased, and high levels of dietary Cu increased, the Cu concentrations in whole body, liver, carcass, gut and gills. Copper levels in the liver strongly reflected the exposure conditions with a corresponding fivefold decrease and a 22-fold increase in Cu concentration. Restricting available Cu caused an exponential decline in whole body Cu concentration from 0.0175 to 0.0069 micromol g(-1) and increased the uptake of waterborne Cu (measured with (64)Cu) by the gills. Conversely, high levels of dietary Cu caused a linear increase in whole body Cu concentration to approximately 0.170 micromol g(-1) and depressed the uptake of waterborne Cu. Waterborne Cu uptake contributed the majority (60 %) of the body's Cu accumulation under Cu-deficient conditions while dietary Cu contributed the majority (99 %) at high dietary levels of Cu. True bioavailability of dietary Cu decreased with increasing levels of dietary Cu concentration, although the absolute amount retained increased. These findings demonstrate an important interaction between dietary and waterborne Cu uptake in fish and provide compelling evidence of a key role for the gill in Cu homeostasis.

Animal Nutritional Physiological Phenomena↗
PubMed1986

Copper-binding proteins in liver of bluegills exposed to increased soluble copper under field and laboratory conditions.

Livers from bluegills exposed to increased soluble copper (Cu) under field and laboratory conditions were analyzed to determine the concentration and distribution of Cu in metalloproteins of different molecular size. Analyses were performed on bluegills collected from the impoundment of the H. B. Robinson Steam Electric Plant (Florence, SC) near the effluent discharge from the power plant, near the water intake to the cooling system, and from a control pond as well as on bluegills exposed under controlled laboratory conditions. Metalloproteins were separated into low molecular weight (LMW), intermediate molecular weight (IMW), and high molecular weight (HMW) fractions by using high-performance liquid chromatography. In the field-exposed bluegills, Cu concentrations in the LMW, IMW, and HMW fractions were highest in bluegills from the discharge site and lowest in those from the control pond. In the laboratory-exposed bluegills, Cu concentrations in the fractions increased with exposure concentration and time. Concentrations of Cu in the LMW protein fraction and pellet of bluegills exposed to 160 micrograms Cu/L appeared to plateau with long exposure times, whereas those in the HMW fraction continued to increase. Bluegills maintained in 80 micrograms Cu/L water at pH 5.5 accumulated lower concentrations of Cu in the LMW and pellet fractions and higher amounts in the HMW than in those maintained in 80 micrograms Cu/L at pH 7.0. Mortality was dependent on exposure concentration and duration and was higher in bluegills maintained in water at pH 5.5 than at pH 7.0.

Animals↗
PubMed2002

Renal copper as an index of copper status in marginal deficiency.

Marginal copper (Cu) deficiency is difficult to study, in part because its effects may be small, but also because feeding of a deficient diet may not cause a discernable change in Cu status. The key to resolution of effects may be in the choice of Cu status index. In this study, liver Cu concentration, a commonly used index of Cu status, was compared with activity of ceruloplasmin (CP), a circulating Cu-dependent enzyme, and kidney Cu concentration for their utility in resolving effects of marginal Cu deficiency. Seventy male, weanling rats were fed diets containing, nominally, 0, 1.5, 3, 4.5, or 6 mg Cu/kg diet for 5 wk. All three indices showed strong depression with severe deficiency (dietary Cu=0), but were relatively weak in their ability to distinguish between animals fed marginally deficient diets when compared by group statistics (ANOVA). Further, group statistics revealed no effect of marginal deficiency on six other variables known to change with severe Cu deficiency: heart weight/body weight, hematocrit, red cell distribution width, neutrophil count, glycated hemoglobin, and platelet count. To take into account interanimal variation, the three putative indices were plotted against these six variables and linear regression was performed on points representing marginally deficient rats. None of the variables showed significant regression with liver Cu or serum ceruloplasmin, but three showed significant regression with kidney Cu. These findings indicate that kidney Cu is preferable to liver Cu or ceruloplasmin as an index of Cu status in marginal deficiency and that linear regression is a possible way of testing for effects of marginal Cu deficiency, especially when effects are subtle.

Analysis of Variance↗
PubMed1979

On the possible involvement of ascorbic acid and copper proteins in leukemia. IV. ESR investigations on the interaction between ascorbic acid and some copper proteins.

The interaction between lyophilized samples of ascorbic acid and some copper proteins (ceruloplasmin, cytochrome-c-oxidase, ascorbate-oxidase) has been investigated by means of ESR spectroscopy. The spectra obtained are identical to the one obtained with leukemic blood. The consequences of this for the molecular events occurring in cancer are discussed. The model proposed can explain the experimental findings reported thus far (such as change in spin concentration with the development of cancer, the presence of a high concentration of antioxidants etc.) as well as reconsile the two existing and seemingly contradictory hypothesis. Possible implications for lipid peroxidation and for the respiratory process are discussed.

Ascorbate Oxidase↗
PubMed2006

Copper binding affinity of S100A13, a key component of the FGF-1 nonclassical copper-dependent release complex.

S100A13 is a member of the S100 protein family that is involved in the copper-dependent nonclassical secretion of signal peptideless proteins fibroblast growth factor 1 and interleukin 1 lpha. In this study, we investigate the effects of interplay of Cu2+ and Ca2+ on the structure of S100A13 using a variety of biophysical techniques, including multi-dimensional NMR spectroscopy. Results of the isothermal titration calorimetry experiments show that S100A13 can bind independently to both Ca2+ and Cu2+ with almost equal affinity (Kd in the micromolar range). Terbium binding and isothermal titration calorimetry data reveal that two atoms of Cu2+/Ca2+ bind per subunit of S100A13. Results of the thermal denaturation experiments monitored by far-ultraviolet circular dichroism, limited trypsin digestion, and hydrogen-deuterium exchange (using 1H-15N heteronuclear single quantum coherence spectra) reveal that Ca2+ and Cu2+ have opposite effects on the stability of S100A13. Binding of Ca2+ stabilizes the protein, but the stability of the protein is observed to decrease upon binding to Cu2+. 1H-15N chemical shift perturbation experiments indicate that S100A13 can bind simultaneously to both Ca2+ and Cu2+ and the binding of the metal ions is not mutually exclusive. The results of this study suggest that the Cu2+-binding affinity of S100A13 is important for the formation of the FGF-1 homodimer and the subsequent secretion of the signal peptideless growth factor through the nonclassical release pathway.

Binding Sites↗
PubMed2005

Delineating copper accumulation pathways for the freshwater bivalve Corbicula using stable copper isotopes.

Delineation of metal uptake routes in aquatic invertebrates is critical for characterizing bioaccumulation dynamics and assessing risks associated with metal exposure. Here we demonstrate that Cu stable isotopic ratios can be manipulated in both exposure media and algae to determine the efflux rate constant (ke) and to estimate Cu assimilation efficiency (AE) from ingested food in a freshwater bivalve (Corbicula fluminea). The Cu AE in Corbicula fed 65Cu-spiked Cryptomonas ozolini was 38%. Copper uptake routes had no significant influence on efflux; ke of 0.004 per day characterized the slowest component of efflux following short-term exposures to 65Cu in water or in both food and water. Incorporation of the physiological parameters for dietary and dissolved uptake as well as rate constants of loss into a bioaccumulation model allowed for assessing the relative contribution of water and food as Cu sources. At [65Cu2+] of 6.7 microg/L, Corbicula accumulated twice as much Cu from diet as from water. In most freshwater systems, the dietary pathway is likely to act as the major Cu uptake route for Corbicula. Extrapolation of our laboratory results to the San Francisco Bay-Delta (California, USA) indicated that our biodynamic model and the laboratory-derived parameters for dietary 65Cu uptake provided a realistic representation of the processes involved in Cu accumulation by the bivalve Corbicula.

Animals↗
PubMedDate not supplied

Fractionation and mobility of copper, lead, and zinc in soil profiles in the vicinity of a copper smelter.

Four soil profiles located near a copper smelter in Poland were investigated for the distribution and chemical fractions of Cu, Pb, and Zn and their mobility in relation to soil properties. Contamination with heavy metals was primarily restricted to surface horizons and the extent of contamination was 7- to 115-fold for Cu, 30-fold for Pb, and 6-fold for Zn as compared with subsurface horizons. In the less-contaminated fine-textured soil, the metals were distributed in the order: residual >> Fe-Mn oxides occluded > organically complexed > exchangeable and specifically adsorbed, while the order for sandy soils was: residual > organically complexed > Fe-Mn oxides occluded > exchangeable and specifically adsorbed. The contaminated surface horizons of these profiles showed no consistent pattern of metal distribution. However, the common features of highly contaminated soils were very low percentage of residual fraction and the dominance of the NH4OAc extractable fraction. The sum of mobile metal fractions was generally < 10% in subsurface horizons, while in the contaminated surface horizons these fractions made up 50% of the total metal contents. Soil properties contributed more to the relative distribution of the metal fractions in the studied profiles than did the distance and direction to the source of pollution. The amounts of metal extracted by 0.01 M CaCl2 accounted for only a small part of the same metals extracted by NH4OAc. The mobility indexes of metals correlated positively and significantly with the total content of metals and negatively with the clay content.

Copper↗
PubMed1994

Effect of dietary copper, iron, and molybdenum on growth and copper status of beef cows and calves.

A study was conducted to determine the effects of copper (Cu) depletion by feeding diets high in either iron (Fe) or molybdenum (Mo) on performance and Cu status of beef cows and calves. Thirty-eight 2-yr-old beef heifers, entering the last one-third of gestation, were randomly assigned by expected calving date to one of four diets: 1) control (CON; corn silage-soybean meal-based diet, 4 mg of Cu/kg), 2) control + 600 mg of Fe (as FeCO3)/kg, 3) control + 5 mg of Mo (as Na2MoO4)/kg, and 4) control + 10 mg of Cu (as CuSO4)/kg. From d 28 until after the end of the calving season (d 125), heifers receiving supplemental Cu had higher (P < .05) plasma Cu levels and ceruloplasmin activities than heifers fed the other diets. By d 224, plasma Cu concentrations of heifers fed the CON and Fe diets had increased to levels similar to those observed in the Cu-supplemented heifers, whereas the Mo heifers exhibited the lowest (P < .05) plasma Cu of the four treatments from d 168 through the remainder of the 280-d trial. Plasma Cu concentrations and ceruloplasmin activities were greater (P < .05) in Cu-supplemented than in non-Cu-supplemented calves (diets 1, 2, and 3) from d 168 onward, and the Fe- and Mo-supplemented calves did not differ in either measurement at any time during the trial. Rate of gain did not differ among calves fed the CON, Fe- or Cu-supplemented diets, whereas the Mo-supplemented calves gained at a much slower (P < .05) rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗