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)

Copper,zinc superoxide dismutase (CuZnSOD), an antioxidant enzyme, is unique in requiring two essential metals for catalytic function. Yet, only one, copper, seems to regulate the expression of functional activity. Restricting dietary copper quickly impairs catalytic functioning of CuZnSOD in numerous tissues. Diets supplemented with copper or small amounts of CuCl2 administered intraperitoneally restore the enzyme activity in animals deprived of copper. Thus, CuZnSOD has been considered a good marker of copper status. A metal-free (apo) form of CuZnSOD could exist in tissues at all times, but especially when an animal is deprived of copper. Restoring CuZnSOD activity with copper permits elucidation of the pathway of copper incorporation into the enzyme. Ceruloplasmin and albumin transport copper to the enzyme in vitro. K562 cells, a human erythroleukemic cell line, can extract copper from ceruloplasmin and incorporate it into CuZnSOD. Ascorbic acid stimulates the transfer of 67Cu transfer from ceruloplasmin to the cells, and somewhat unexpectedly, appears to restrict the amount of transferred copper that becomes bound to the enzyme. Reactivation of CuZnSOD in healthy individuals has the potential of being a useful tool for assessing copper status. This approach has merit, but one must consider that the levels of apo-enzyme that prevail in tissue could be influenced by other metals.
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PMID:Copper as a cofactor and regulator of copper,zinc superoxide dismutase. 154 24

Scurvy-like symptoms have been seen in experimental copper deficiency. This forecasts a role for the vitamin in copper metabolism. Ascorbate has been known to antagonize the intestinal absorption of copper. More recent studies have characterized a postabsorption role for ascorbate in the transfer of copper ions into cells. The vitamin reacts directly or indirectly with ceruloplasmin, a serum copper protein, specifically labilizing the bound copper atoms and facilitating their cross-membrane transport. Ascorbate at physiological levels and above impedes the intracellular binding of copper to Cu,Zn superoxide dismutase. The mechanism is unclear but nonetheless suggests both positive and negative regulatory functions for ascorbate in copper metabolism.
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PMID:A role for ascorbic acid in copper transport. 196 69

Copper uptake from 67Cu-labeled ceruloplasmin (67CuCp) was studied in K-562 cells, a human erythroleukemic cell line. 67CuCp was prepared by an ascorbate-catalyzed exchange of recrystallized ceruloplasmin with 67CuCl2. The labeled protein was treated with Chelex-100 and gel filtration to ensure that 67Cu was tightly bound to the structure. 67CuCp bound specifically to the K-562 cells at 4 degrees C. The binding was linear with protein in the range of 200-800 nM and in the presence of 3% albumin. In this concentration range, 67CuCl2 showed no binding that could be interpreted as specific; 80-90% of the cell-bound 67Cu was removed by washing the cells with acid buffer. When binding was attempted at 37 degrees C, a significant fraction of the 67Cu resisted acid washing and with time accumulated in the cells. Fractionating the cytosolic components on Percoll gradients located the 67Cu in buoyant fractions of densities 1.030-1.05, with a peak at 1.035. Repeating the experiment with 125I-labeled ceruloplasmin failed to localize any 125I label in Percoll fractions; very little 125I was detected in the cytosol. Double-labeled 67Cu-125I-ceruloplasmin confirmed that copper and not the protein moiety of ceruloplasmin was taken up by the cells. The uptake reaction was inhibited by 1 mM bathocuproine sulfonate and by 1 mM sodium iproniazid. Ascorbate (100 microM) strongly stimulated uptake. These studies provide evidence that K-562 cells are able to extract copper atoms from ceruloplasmin and transport the copper to the cytosol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Copper transport from ceruloplasmin: characterization of the cellular uptake mechanism. 230 61

Ceruloplasmin binds to the membranes of K562 cells. The binding has been shown to result in a temperature-dependent transfer of ceruloplasmin-bound copper into the cytosol. Ascorbic acid (100 microM) stimulates the transmembrane transfer nearly 10-fold, depending on the initial concentration of 67Cu-ceruloplasmin. The protein moiety of ceruloplasmin does not enter the cells. Bathocuproine disulfonate, a chelator specific for cuprous copper, inhibits the uptake, suggesting copper atoms are reduced concomitant with their removal from ceruloplasmin. Cytosolic 67Cu from ceruloplasmin was found mainly bound to Cu, Zn superoxide dismutase, the major cytosolic copper protein in these cells. Evidence supporting the various phases in the ceruloplasmin-mediated transport mechanism are presented.
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PMID:Copper transport: insights into a ceruloplasmin-based delivery system. 262 93

Copper uptake from human ceruloplasmin (Cp) into cells of a human erythroleukemic cell line, K562, was investigated. The interaction between ascorbic acid and the copper atoms in ceruloplasmin was a focal point of the study. Nondenatured 67Cu-labeled ceruloplasmin (67Cu-Cp) was prepared by an ascorbate-catalyzed exchange of Cp with 67CuCl2 in vitro. The complex was stable, even in the presence of 1.0 mM ascorbate. Adding K562 cells and incubating at 37 degrees C resulted in an immediate transfer of 67Cu from ceruloplasmin to the cells. At 37 degrees C the copper accumulated by the K562 cells resisted dissociation by mild acid washing. The rate of transfer of 67Cu was proportional to the Cp concentration in the medium. Ascorbate (100 microM) enhanced the uptake of 67Cu at least fourfold. D-Isoascorbate worked as well as L-ascorbate, suggesting that the reducing potential of the vitamin (or its isomer) was important in the uptake of copper. Approximately 20% of the 67Cu absorbed into the cytosol was precipitable with antibodies to Cu-Zn superoxide dismutase (Cu-Zn SOD). Ascorbate, however, did not enhance the incorporation of radioactivity into Cu-Zn SOD, suggesting that copper may not be the only rate-limiting factor in the synthesis of this enzyme in K562 cells. The possible relevance of these observations to vitamin C deficiency is discussed.
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PMID:Ascorbate enhances copper transport from ceruloplasmin into human K562 cells. 272 26

Ascorbic acid (AsA), added to nutrient broth at a concentration of 5 mmol/l, was bactericidal towards Campylobacter jejuni grown at 42 degrees C in a micro-aerobic atmosphere. Specific enzymes, radical scavengers, metal chelators and reducing agents were tested as possible antagonists to the cytotoxicity of AsA. The addition of catalase or of the metal chelators ceruloplasmin or Desferal did not prevent the cytotoxic effect of AsA. The addition of the hydroxyl radical scavengers mannitol, formate, histidine or DMSO also failed to counteract the toxicity of AsA. On the other hand, thiourea or cysteamine and the reducing agents cysteine or dithionite significantly increased the recovery of C. jejuni in the presence of AsA. Although the possibility of the involvement of hydroxyl radicals in AsA cytotoxicity cannot be ruled out, it appears that the toxic effect of AsA is due mostly to the formation of products of oxidation of AsA and particularly to dehydroascorbic acid (DHA). Dehydroascorbic acid was also bactericidal to C. jejuni at a concentration of 5 mmol/l. Of all the compounds tested, only cysteamine was effective in preventing (partially) the toxic effect of DHA. The growth of C. jejuni was not inhibited by the addition of 5 mmol/l of isoascorbic acid or sodium isoascorbate.
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PMID:Effect of ascorbic, isoascorbic and dehydroascorbic acids on the growth and survival of Campylobacter jejuni. 378 41

The pathogenesis of Menkes disease seems to be linked to metallothionein which binds to copper trapped within cells in some tissues. The only known therapy for this disease is parenteral administration of copper, but the effects are equivocal. We treated a patient with Menkes disease by giving vitamin C orally. The clinical manifestation and bone changes improved and the plasma copper and ceruloplasmin levels gradually increased. Vitamin C may prevent the binding of copper and metallothionein by its reducing effect, and excess copper would be released from the cells. Vitamin C treatment is a simple and physiological method, and should aid in clarifying the pathogenesis of the disease.
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PMID:Menkes disease: is vitamin C treatment effective? 408 90

A 2 X 2 factorial arrangement with two levels (0, 660 ppm) of vitamin C and two levels (0, 55 ppm) of carbadox supplementation was used in two experiments with 112 crossbred pigs weaned between 4 and 5 wk of age. An 18% protein corn-soybean meal-oats-dried whey starter diet was used as the basal diet. Each diet was fed ad libitum for a 4-wk period to three replicates of four pigs in Exp. 1 and to four replicates of four pigs in Exp. 2. Vitamin C supplementation produced a significantly higher plasma vitamin C concentration in weanling pigs, but, contrary to results of our previous study, failed to improve average daily gain of the pigs. Daily gain was, however, improved significantly by carbadox supplementation. Carbadox also produced a significantly higher plasma vitamin C concentration in pigs after a 7-d lag period. Plasma Fe concentration of pigs was not affected by supplemental vitamin C, but was significantly higher in those fed carbadox-supplemented diets. Plasma ceruloplasmin concentration increased significantly in all treatment groups from the initial sampling period (d 0) to subsequent periods. No interactions between supplemental vitamin C and carbadox were observed in daily gain, feed efficiency and the measured plasma constituents.
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PMID:Responses of weanling pigs to dietary supplementation with vitamin C or carbadox. 669 94

Copper ion induced lysis of rat erythrocytes was markedly stimulated by low concentrations of ascorbate and dehydroascorbate. Ascorbate oxidase, superoxide dismutase, catalase or scavengers of hydroxyl radicals protected erythrocytes against copper-ascorbate stimulated lysis. It is proposed that superoxide radicals and hydrogen peroxide cooperate in producing hydroxyl radicals, which are directly involved in hemolysis. The serum proteins, ceruloplasmin, albumin and apotransferrin, also reduced the hemolytic action of copper-ascorbate, the order of effectiveness being; ceruloplasmin greater than albumin greater than apotransferrin.
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PMID:Ascorbate (vitamin C) and dehydroascorbate stimulation of copper induced hemolysis. Protective action of ceruloplasmin, albumin and apotransferrin. 670 67

Ascorbic acid (AA) metabolism was studied in six sexually mature female rhesus monkeys with normal menstrual cycles before and during oral contraceptive administration. The animals were fed a commercial monkey stock diet (15% protein) containing no AA and given a 100 mg AA tablet daily throughout the study. After an initial adaptation period and a control period (total 8 months), combined-type oral contraceptive agents (OCAs) (50 micrograms mestranol and 1 mg norethindrone for 21 days each month) were administered to each monkey for 4 months. Serum copper and ceruloplasmin were significantly elevated during OCA treatment. There were no significant changes in plasma or leukocyte AA values during OCA use; however, urinary AA excretion decreased significantly. During the last month of the control period and the 3rd month of OCA treatment, 50 muCi of 1-14C-L-ascorbic acid were injected intravenously into each monkey. Urinary excretion of radioactivity, measured for 1 month, indicated a significantly faster AA turnover rate during the period of OCA use. These results suggest that women using OCAs may have an increased dietary requirement for AA.
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PMID:Effect of oral contraceptive agents on ascorbic acid metabolism in the rhesus monkey. 708 Nov 22


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