Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The effects of moderately elevated zinc (Zn) intake on copper (Cu) metabolism and on the pancreas were studied. Zn (80 mg/L) as acetate was added to the drinking water of male Swiss mice for up to 12 weeks, which increased the total daily Zn intake to about 5 times the adequate level. Total Cu and Zn in tissues was measured by atomic absorption spectrometry. 64Cu was used to measure some effects of the Zn suppletion on the Cu metabolism. Furthermore, ceruloplasmin and amylase in plasma and superoxide dismutase in erythrocytes were measured. The pancreas was examined by light microscopy. The Zn supplementation decreased the 64Cu absorption and increased the retention of 64Cu, but did not lead to a Cu deficiency. Microscopic examination of the pancreas revealed focal hypertrophy of acinar cells, occasionally accompanied by vacuolation of cytoplasm and/or the presence of degenerated cells. The results, obtained in mice given a moderately increased Zn intake, should be interpreted as a warning against the chronic use in man of high doses of Zn for non-medical purposes.
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PMID:Effects of elevated zinc intake on the copper metabolism and the pancreas of the mouse. 138 53

TE-5 is an essential trace element agent containing iron, zinc, copper, manganese and iodine for total parenteral nutrition (TPN). We have already reported that TE-5 improved the reduction of trace element concentrations induced by TPN. However, effects of TE-5 on the changes in biological function relating to trace elements are poorly understood. The present study was designed to clarify the effects of TE-5 on these functions. Rats fed a trace element (iron, zinc, copper, manganese and iodine)-deficient diet for 7 weeks showed reductions in the following parameters: plasma and various tissue concentrations of iron, zinc, copper, manganese and iodine, growth rate, erythrocyte (iron), hemoglobin (iron), hematocrit (iron), mean corpuscular constants (iron), plasma alkaline phosphatase activity (zinc), serum ceruloplasmin concentration (copper), liver pyruvate carboxylase activity (manganese) and serum thyroxine concentration (iodine). On the other hand, when TE-5 (0.008, 0.04 and 0.2ml/kg: x 0.2, x 1 and x 5 the usual clinical dose, respectively) was intravenously administered once a day for 7 weeks under the conditions described above, there was a tendency to prevent the reductions of plasma and various tissue concentrations of iron, zinc and manganese. In addition, TE-5 prevented the reductions of growth rate, iron metabolism functions, plasma alkaline phosphatase activity, serum ceruloplasmin concentration and liver pyruvate carboxylase activity. The present study shows that TE-5 prevents both reductions of trace element contents and trace element-related functions, and suggests that TE-5 is useful for treatment of trace element deficiency in TPN.
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PMID:[Effects of an essential trace element agent (TE-5) for total parenteral nutrition on the mineral nutrition in rats fed a trace element-deficient diet]. 144 33

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

Several recent studies have shown decreased copper and increased zinc concentrations in the substantia nigra and increased copper concentrations in the cerebrospinal fluid of Parkinson's disease patients. To elucidate whether changes in serum levels of these trace elements may increase the risk of developing Parkinson's disease (PD), we assessed serum levels of zinc and copper by flame atomic absorption spectrophotometry, and albumin and ceruloplasmin, in 32 (Zn) and 39 PD patients (Cu), respectively, with their spouses as the control group. Serum zinc, albumin, copper and ceruloplasmin levels and the zinc/albumin and copper/ceruloplasmin ratios, did not differ significantly between the two groups and were not influenced by antiparkinsonian therapy in the PD patients. Serum zinc/albumin ratio (r = 0.43), ceruloplasmin (r = -0.36) and copper/ceruloplasmin ratio (r = 0.36) correlated significantly with age, but not with age of onset, duration of the disease, scores of the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr staging in PD patients. These values did not correlate with age in the control group. These results suggest that serum levels of zinc and copper do not play any role as risk factors for PD.
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PMID:Serum levels of zinc and copper in patients with Parkinson's disease. 146 36

The serum copper and zinc concentration, the Cu/Zn ratio and ceruloplasmin activity have been studied in 400 subjects divided into 4 groups of study: 50 normal subjects (controls), 100 patients with ischemic heart disease, 100 subjects with myocardial infarction in the past history and 150 patients with acute myocardial infarction. It was observed that in normal subjects the Cu/Zn ratio is about 1, in acute myocardial infarction it reaches 2.5 but it returns to normal during convalescence. In the patients with ischemic heart disease the ratio decreases to 0.8 and in the subjects with infarction in the past history it is about 1.6 (almost normal). The variation of these ratio is due to the serum zinc concentration which in ischemic heart disease presents values over the upper normal limit and in acute myocardial infarction below the lower normal limit. In the subjects with acute infarction ceruloplasmin (copper depending enzyme) the activity was observed to be inversely proportional to the Cu/Zn ratio in the first 4 days after the onset of the disease. The quick normalization of one or of both parameters is a sign of positive evolution of the disease.
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PMID:Study of serum ceruloplasmin and of the copper/zinc ratio in cardiovascular diseases. 147 97

Due to the stress imposed by the process of bone marrow transplantation (BMT), we hypothesized that individuals receiving such a transplant underwent an acute phase response (APR). Circulating levels of C-reactive protein (CRP), haptoglobin (HAP), alpha-1 acid glycoprotein (AAG), ceruloplasmin (CER), zinc (Zn), copper (Cu), interleukin-6 (IL-6), albumin (ALB), and thyroxine-binding prealbumin (TBPA), were measured at baseline (Day -7), Day -4, Day 0 (Transplant Day), Day +2, +7, and weekly until day 28 in 14 adults receiving an autologous bone marrow transplant as Phase 1 treatment for various hematologic or solid tumor malignancies. Ten of 14 recipients survived, 9 of which had a significant increase in CRP (p = 0.012), HAP (p = 0.011), AAG (p = 0.002), and decrease in ALB (p = 0.002) and TBPA (p = 0.004) on Day +7, but not Day 0, after bone marrow reinfusion. These findings document the presence of an APR and suggest that the bone marrow transplant process (post reinfusion) initiates a stress response in the recipient.
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PMID:The acute phase response in autologous bone marrow transplantation. 147 99

In the present study we have used differential centrifugation, size exclusion chromatography, Western and Northern blotting to investigate the subcellular distribution of hepatic copper, the association of the metal with hepatic copper binding proteins and the expression of specific mRNAs for copper binding proteins in liver tissue from two patients with Wilson's disease, two patients with chronic liver disease and two patients with normal hepatic copper levels. Unlike previous studies the present results fail to show any gross differences in subcellular distribution of copper between the livers, with most of the copper being found in the soluble supernatant where it is associated with metallothionein. Caeruloplasmin mRNA levels were reduced in the two patients with Wilson's disease and also in a patient with fulminant hepatic failure. It remains to be confirmed if the reduction of caeruloplasmin mRNA is specific for Wilson's disease. Levels of mRNAs for copper zinc superoxide dismutase and metallothionein were variable and not related to liver copper.
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PMID:Copper metabolism in hypercupremic human livers. Studies of its subcellular distribution, association with binding proteins and expression of mRNAs. 150 62

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

Erythrocyte antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and reduced glutathione, serum ceruloplasmin, and serum trace elements (copper, zinc, iron, and selenium) related to antioxidant enzymes were assayed in subjects with alcoholic liver disease of different degrees of severity. The erythrocytes of subjects with moderate and severe alcoholic liver cirrhosis had an unbalanced antioxidant system (normal superoxide dismutase, low catalase and glutathione peroxidase activities, and low glutathione content). Serum ceruloplasmin levels were in the normal range. Levels of the serum trace elements zinc and selenium were significantly low in subjects with moderate and severe cirrhosis, whose red cell half-life was also significantly short, as measured by radioactive chromium. These data suggest that the erythrocytes of subjects with moderate and severe alcoholic liver cirrhosis are less protected against oxidant stress. The particular erythrocyte antioxidant system and serum trace element pattern may play a role in the genesis of hemolytic disorders and of alcoholic hepatic damage.
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PMID:Erythrocyte antioxidant activity, serum ceruloplasmin, and trace element levels in subjects with alcoholic liver disease. 837 44

Inflammation, an acute phase stress, alters copper (Cu) metabolism, but effects on human Cu requirements are unknown. Cu supplementation (2 mg/day, 4 weeks) increased erythrocyte Cu-zinc (Zn) superoxide dismutase (SOD) activity levels in 18 of 23 rheumatoid arthritis (RA) patients receiving gold or methotrexate (mean increase 21%). SOD values were significantly lower in RA patients than in 47 age- and sex-matched controls before, but not after supplementation. Supplementation did not significantly affect ceruloplasmin (Cp) activity or protein concentrations in either group. However, RA subjects showed significantly lower Cp activity to protein ratios compared to controls, before and after supplementation. Cu supplementation did not affect acute phase status of RA patients as evidenced by unchanged serum alpha-1-acid glycoprotein levels. In conclusion, the effects of Cu supplementation on erythrocyte SOD activities suggested a trend toward marginal Cu status in RA patients.
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PMID:Effects of copper supplementation on ceruloplasmin and copper-zinc superoxide dismutase in free-living rheumatoid arthritis patients. 157 95


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