Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dietary antagonism between copper and molybdate salts prompted a study of the inhibition of copper enzymes by thiomolybdate (TM). TM strongly inhibited the oxidase activity of five copper oxidase with I50% values in the 1-5 microM range. The mechanism of the TM effect on the copper oxidase, ceruloplasmin (Cp) (E.C. 1.16.3.1), was studied in detail. In Vmax vs. E plots, TM gave parallel data suggesting irreversibility but a large number of TM molecules per Cp were required. The inhibition of Cp by TM could not be reversed by dialysis. Isolation of TM-inhibited Cp on Sephadex G-10 did not yield any active Cp molecules. Cu(II) did not restore any inhibited oxidase activity. Gel electrophoresis supported the covalent binding of Cp by TM without any extensive change in protein structure. EPR results confirmed that Cu(II) is reduced to Cu(I) after reaction with TM. However, the Mo(VI) in MoS4(2-) did not change in oxidation number. Analysis of the TM-Cp compound accounted for all six Cu atoms as found in native Cp. The data suggest the covalent binding of sulfide to Cp copper. TM also inhibited the activity of ascorbate oxidase, cytochrome oxidase, superoxide dismutase, and tyrosinase. However, no inhibition of carbonic anhydrase, a zinc enzyme, was observed at 1 mM TM.
 ...
PMID:Inhibition of ceruloplasmin and other copper oxidases by thiomolybdate. 609 47

Metabolic studies in tumor cells have indicated that bioenergetic regulatory mechanisms geared to acute changes in oxygen availability are abnormal. In the present studies we have examined bioenergetic adaptations to chronic oxygen depletion in culture maintained tumor cells in comparison to normal cell lines. Activities of two key glycolytic enzymes (pyruvate kinase (PyKI) and phosphofructokinase (PFK)) were measured in two tumor cell lines (fibrosarcoma (FS) and Hela) and two normal cell lines (rat lung fibroblasts (RLF) and WI-38) maintained in culture for up to 96 hours under aerobic (PO2 approximately 140) and hypoxic PO2 approximately 15) conditions. Exposure to low O2 tensions for 96 hours resulted in significant increases in PyKi and PFK in both RLF and WI-38, ut did not alter activities of these enzymes in either FS or HeLa cell systems. Activities of two enzymes involved in O2 metabolism (cytochrome oxidase (CyOx) and superoxide dismutase (SOD) were also measured in the two tumor cell lines and in RLF. chronic hypoxia significantly decreased the activities of CyOx and SOD in RLF cell systems but did not alter the activities of these enzymes in the tumor cells. In these studies, the tumor-derived cell lines do not demonstrate specific enzymatic responses to sustained oxygen depletion in vitro noted in normal cell systems, suggesting significant abnormalities in regulatory mechanisms geared to chronic changes in molecular O2.
 ...
PMID:Differences in oxygen-dependent regulation of enzymes between tumor and normal cell systems in culture. 627 Jan 67

Nitrite causes changes in the optical and EPR spectra of cytochrome oxidase from heart and alters the spectral, redox and basic properties of cytochrome c. No utilization of nitrite by cytochrome oxidase was observed. However, nitrite inhibits the superoxide dismutase and oxidase activities of the enzyme. Changes in the properties of cytochrome oxidase were observed under effect of some products of nitrite reduction, e. g. nitric oxide, hydroxylamine, hydrazine; nitrate has no effect on the optical and EPR spectra or on the enzyme activity.
 ...
PMID:[Effect of nitrite on cytochrome oxidase]. 627 Dec 65

Chronic copper deficiency in mice impairs both humoral and cell-mediated immunity, but the mechanisms are unknown. Copper deficiency was produced in C58 mice by feeding dams a diet low in copper throughout lactation and weaning the pups to this diet. Control mice were from dams fed the same diet but with copper supplementation the drinking water. Six-week-old mice were sampled for biochemical and morphological studies. Compared to copper-supplemented mice, copper-deficient animals were smaller, anemic and exhibited hypoceruloplasminemia. The copper-deficient mice have small thymus glands, enlarged spleens, and livers equivalent in size to copper-supplemented mice. Thymic atrophy is not caused by elevated serum corticosterone. Liver, spleen, and thymus tissues from copper-deficient mice exhibit low cytochrome oxidase (56, 38, and 45%, respectively) and superoxide dismutase activities (61, 60, and 43%, respectively) compared to tissues from copper-supplemented mice, indicating a functional copper deficiency. Electron micrographs taken of thymus and spleen from copper-deficient mice demonstrate altered morphology characterized by abnormal mitochondria and misshapen nuclei. Chronic copper deficiency alters the size, biochemistry and morphology of primary (thymus) and secondary (spleen) lymphoid tissue.
 ...
PMID:Chronic dietary copper deficiency alters biochemical and morphological properties of mouse lymphoid tissues. 630 92

Kale (Brassica oleracea) and ryegrass (Lolium perenne)-clover (Trifolium repens) pasture grown under similar soil conditions were grazed in the vegetative state by growing lambs of 23.6 kg initial live weight for 24 weeks. Forty-eight lambs grazed each forage. The kale and pasture contained respectively 4 and 14 mg copper/kg dry matter (DM), 7.2 and 3.1 g total sulphur/kg DM and 0.4 and 1.1 mg molybdenum/kg DM. Subcutaneous injections of Cu (12 mg) were given to half the animals grazing each forage during weeks 1, 6, 12 and 18. All ninety-six animals were slaughtered at the end of the experiment and an additional group of twelve animals was slaughtered when the experiment commenced. Liver Cu was determined on all slaughtered animals and heart muscle cytochrome oxidase (EC 1.9.3.1) activity on those slaughtered at week 24. Blood samples removed at 6-week intervals were assayed for activity of superoxide dismutase (EC 1.15.1.1; SOD) and serum Cu concentration determined. Wool growth, live-weight gain and cytochrome oxidase activity of biopsied hind-limb muscle were also measured at 6-week intervals. Control animals grazing pasture showed an accumulation of total liver Cu during the experiment. Animals grazing this diet and given Cu injections showed an additional accumulation of liver Cu equivalent to the supplementary Cu administered, but Cu supplementation did not affect the activity of any of the Cu-containing enzymes measured and did not affect live-weight gain or wool growth. Control animals grazing kale showed a depletion of total liver Cu and reductions in serum Cu concentrations during weeks 18 and 24.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Copper metabolism in growing sheep given kale (Brassica oleracea) and ryegrass (Lolium perenne)-clover (Trifolium repens) fresh forage diets. 631 Dec 44

Rats exposed to 10 to 11 per cent oxygen for 7 days develop tolerance to hyperoxia and can survive for prolonged periods in 100 per cent oxygen. This preexposure to hypoxia is associated with a 180 per cent increase in the activity of the mangani superoxide dismutase but no increase in activity of copper-zinc superoxide dismutase, glucose-6-phosphate dehydrogenase, or the mitochondrial enzymes, cytochrome oxidase and succinate cytochrome c reductase. Cyanide-insensitive oxygen uptake is also increased after this exposure to hypoxia suggesting that an enhanced rate of production of partially reduced species of oxygen may occur. Morphometric and morphologic studies of lung structure demonstrate that no substantial change in cell population characteristics occur in the lungs of animals exposed to hypoxia, but there are ultrastructure changes in the cytoplasm of pulmonary capillary endothelial cells consistent with focal hypertrophy and enhanced metabolic activity of these cells.
 ...
PMID:Structural and biochemical adaptive changes in rat lungs after exposure to hypoxia. 682 93

The homogenate of loach (Misgurnus fossilis) embryonic cells was fractionated by differential centrifugation into fractions, in which the activities of DNA polymerases alpha and gamma were measured. About half of the total alpha-polymerase activity was retained in the postmicrosomal supernatant. The activity of gamma-polymerase in the supernatant did not exceed 2% of the total activity. The specific activity of gamma-polymerase was maximal in the mitochondrial pellet. The enzyme activity in the nuclear pellet was proportional to the activity of mitochondrial enzymes, cytochrome oxidase and KCN-insensitive superoxide dismutase. The nuclei were separated from gamma-polymerase-containing fraction by ultracentrifugation in a 10-50% sucrose density gradient. The material of this fraction was identical to the mitochondria in terms of buoyant density, morphology and enzymatic properties. Thus, in loach embryos the fraction of gamma-polymerase associated with the nuclei is absent; the total gamma-polymerase activity is localized in the mitochondria.
 ...
PMID:[DNA polymerase gamma in the cells of loach embryos localized in mitochondria]. 688 27

The role of copper in maintaining normal neurological function has been examined in animals copper-deficient by dietary means, and in the genetic disorders of copper homeostasis -- Menkes' kinky-hair disease in humans and the mottled (Mo) mutants in the mouse. With the exception of the disorder in Mo mice, reduced myelination is a constant feature of these copper diseases but there is otherwise a lack of conformity in the structural defects produced in different species. Dietary copper-deficient animals show a reduction in noradrenaline and dopamine concentrations, together with a depressed tyrosine 3-monooxygenase activity (EC 1.14.16.2). Noradrenaline concentrations are also reduced in brain tissue of Mo mice and this reduction is associated with a decrease in the vivo activity of the copper metalloenzyme, dopamine beta-monooxygenase (EC 1.14.17.1). Many tissues contain potent inhibitors of dopamine beta-monooxygenase activity, and assays of this enzyme have utilized cupric ions to inactivate these inhibitors. The elevated in vitro activities of dopamine beta-monooxygenase obtained for both Mo brain and adrenal tissue may therefore reflect either a reduced inactivation of these endogenous inhibitors in the intact animal or the activation in vitro of apoenzyme. Concentrations of dopamine and tyrosine 3-monooxygenase are unchanged in Mo mice. The reduction in dopamine and tyrosine 3-monooxygenase activity in dietary copper-deficient animals may therefore reflect neuronal loss rather than reduced catalytic activity of the catecholamine biosynthetic pathway. The possible effects of depressed activities of cytochrome c oxidase (EC 1.9.3.1) and superoxide dismutase (EC 1.15.1.1) in the development of neurological dysfunction are also discussed, and attention is drawn to the possible significance of the elevated uptake of neutral amino acids, especially tyrosine and tryptophan, by Mo brain tissue.
 ...
PMID:Copper and neurological function. 690 87

With the completion of the primary structure of the 50,000- and 19,000-dalton fragments of human ceruloplasmin [ferroxidase; iron(II):oxygen oxidoreductase, EC 1.16.3.1], over half of the covalent structure of the single polypeptide chain of this protein is known. Visual and computer analysis of the sequence of the 564 amino acid residues in the two fragments gives clear evidence of statistically significant internal homology suggestive of evolutionary replication of two smaller units. Two homology regions, each composed of 224 residues, were defined by an intrasequence alignment that required only three gaps in each 224-residue segment. The two homology regions exhibited 43% identity in sequence, and 13% of the remaining positions had similar residues. The sequence of a 160-residue segment in ceruloplasmin exhibits significant homology to the active (copper-binding) sites of blue electron-transfer proteins such as azurins and plastocyanins and multicopper oxidases such as cytochrome oxidase and superoxide dismutase. It is proposed that a primitive ceruloplasmin gene was formed by the fusion of two genes coding, respectively, for protein abut 160 and 190 amino acid residues in length and that this precursor gene coding for about 350 amino acids was later triplicated to form the gene for the present-day ceruloplasmin molecule of about 1050 amino acids.
 ...
PMID:Internal duplication and evolution of human ceruloplasmin. 694 4

1. A protein with cyanide-sensitive superoxide dismutase activity was isolated from the prokaryote Paracoccus denitrificans. 2. This enzyme, present in low amount in the cell, represented not more than 10% of the total cellular superoxide dismutase activity. It was obtained in a form which was 20-40-times less active than the main superoxide dismutase of P. denitrificans which is a manganese-containing enzyme. 3. It was a soluble monomeric enzyme, highly negatively charged (pI = 4.8), with an apparent molecular weight of 33,000. 4. Cyanide sensitivity was observed by NMR assay, enzyme assay and by staining the protein for superoxide dismutase activity on polyacrylamide electrophoretogram. KCN was shown to be a competitive inhibitor of this dismutase, with an inhibitor constant of 0.15 mM. 5. From the amino acid analysis, S delta Q values lower than 100 were obtained with copper-containing proteins such as the subunit II of cytochrome oxidase from P. denitrificans (69), the azurin from P. denitrificans (77), the bacteriocuprein from Photobacter leiognathi (71); with iron and manganese superoxide dismutases (40-88), and with some eukaryotic copper/zinc dismutases of fish origin (55-82).
 ...
PMID:Isolation and characterization of a protein with cyanide-sensitive superoxide dismutase activity from the prokaryote, Paracoccus denitrificans. 706 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>