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)

Until now o-dianisidine was used as an indicator substance in a test system for the determination of diamine oxidase. More recently, however, this substance was also used to measure ceruloplasmin activity. A study of the test principles revealed that o-dianisidine was the one denominator for both enzymes. As it was found for diamine oxidase the indicator was oxidized via peroxidase mediated H2O2 cleavage. Ceruloplasmin, however, oxidized o-dianisidine directly with resulting free radical formation. An addition of histamine dihydrochloride or putrescine dihydrochloride to an incubation mixture, containing ceruloplasmin as enzyme and o-dianisidine or p-phenylene-diamine as substrates, produced an activation of the enzyme, being more than 10-fold in the presence of 1 X 10(-2) M putrescine at pH 7.0. It was assumed that an allosteric effect of the dihydrochloride component might be responsible for this activation. When the activity of purified diamine oxidase was determined by the o-dianisidine test and by the isotope assay, a very good correlation between both methods was found. But, in a mixture of diamine oxidase and ceruloplasmin, no differentiation between the two enzymic activities by the o-dianisidine test was possible. This observation demonstrated an interference of ceruloplasmin when the o-dianisidine method was used for the determination of diamine oxidase activity. To apply our findings also in vivo the amine oxidase activity increasing in guinea-pig plasma during inflammation, was determined by the o-dianisidine test and by specific methods for some amine oxidase. Despite an enhanced oxidation of the o-dianisidine observed, only an increase of ceruloplasmin activity was found. It was concluded that ceruloplasmin had no 'histaminase activity' as has been assumed by other authors using the o-dianisidine test.
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PMID:Determination of histaminase (diamine oxidase) activity by o-dianisidine test: interference of ceruloplasmin. 40 58

The oxidation chemistry and biochemistry of the serotonergic neurotoxin 5,7-dihydroxytryptamine (1) has been studied under anaerobic and aerobic conditions in aqueous solution at physiological pH. Under anaerobic conditions, one-electron oxidants (ferricytochrome c, peroxidase/H2O2, ceruloplasmin, Cu2+) generate a radical intermediate. Dimerization of the C(6)-centered resonance form of this radical followed by secondary oxidations yields 3-(2-aminoethyl)-6-[3-(2-aminoethyl)-1,7-dihydro- 5-hydroxy-7-oxo-6H-indol-6-ylidene]-1-H-indole-5,7(4H,6H)-dione. Under aerobic conditions, molecular O2 attacks the C(4)-centered 1 radical to yield a hydroperoxy radical which decomposes to 5-hydroxytryptamine-4,7-dione (2). Autoxidation of 1 proceeds by primary attack by molecular O2 on a C(4)-centered carbanion to form a superoxide-radical complex. This rearranges to a C(4)-centered hydroperoxide which decomposes to 2. A C(6)-centered carbanion of 1 combines with 2 to give, ultimately, 6,6'-bi-5-hydroxytryptamine-4,7-dione (3). Trace concentrations of transition metal ions (Fe3+, Fe2+, Cu2+, Mn2+) catalyze the autoxidation of 1 by catalytic cycles in which a hydroperoxide intermediate plays key roles. A byproduct of the transition metal-catalyzed oxidation of 1 is superoxide, O2-. Because of its enormous basicity O2- facilitates deprotonation of 1. The C(4)-centered carbanion so produced is oxidized by molecular O2 or by the hydroperoxy radical (HO2) to give radical intermediates and thence 2 and 3. Mechanistic pathways leading to the various products of oxidation of 1 are proposed and the potential roles of oxidation reactions of the indolamine are related to its neurodegenerative properties.
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PMID:Chemical and enzyme-mediated oxidation of the serotonergic neurotoxin 5,7-dihydroxytryptamine: mechanistic insights. 131 96

Phagocyte-mediated oxidant damage to vascular endothelium is likely involved in various vasculopathies including atherosclerosis and pulmonary leak syndromes such as adult respiratory distress syndrome. We have shown that heme, a hydrophobic iron chelate, is rapidly incorporated into endothelial cells where, after as little as 1 h, it markedly aggravates cytotoxicity engendered by polymorphonuclear leukocyte oxidants or hydrogen peroxide (H2O2). In contrast, however, if cultured endothelial cells are briefly pulsed with heme and then allowed to incubate for a prolonged period (16 h), the cells become highly resistant to oxidant-mediated injury and to the accumulation of endothelial lipid peroxidation products. This protection is associated with the induction within 4 h of mRNAs for both heme oxygenase and ferritin. After 16 h heme oxygenase and ferritin have increased approximately 50-fold and 10-fold, respectively. Differential induction of these proteins determined that ferritin is probably the ultimate cytoprotectant. Ferritin inhibits oxidant-mediated cytolysis in direct relation to its intracellular concentration. Apoferritin, when added to cultured endothelial cells, is taken up in a dose-responsive manner and appears as cytoplasmic granules by immunofluorescence; in a similar dose-responsive manner, added apoferritin protects endothelial cells from oxidant-mediated cytolysis. Conversely, a site-directed mutant of ferritin (heavy chain Glu62----Lys; His65----Gly) which lacks ferroxidase activity and is deficient in iron sequestering capacity, is completely ineffectual as a cytoprotectant. We conclude that endothelium and perhaps other cell types may be protected from oxidant damage through the iron sequestrant, ferritin.
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PMID:Ferritin: a cytoprotective antioxidant strategem of endothelium. 151 45

Phospholipid peroxidation of unsaturated phospholipid liposomes in the tyrosinase(mushroom)-4-hydroxyanisole system was studied in both the presence and absence of Fe3+, as a model of melanocyte damage by this agent. Ferric ion is required for the lipid peroxidation, and maximal lipid peroxidation was achieved with a molar ratio of [Fe3+]/[4-hydroxyanisole] of about 1. The lipid peroxidation was significantly inhibited by ceruloplasmin (a ferroxidase), indicating that Fe3+, which would be coordinated with metabolites, catechols, should be reduced to express its oxidant property. Judging from the results obtained with inhibitors or scavengers of active oxygen species, O2-, H2O2, and .OH would not mainly involve in the lipid peroxidation.
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PMID:Importance of iron in lipid peroxidation in the tyrosinase/4-hydroxyanisole system: possible mechanism of killing of malignant melanoma cells by 4-hydroxyanisole. 162 52

Tyrosinase (EC 1.14.18.1)/O2, ceruloplasmin (human type X)/O2, and peroxidase (EC 1.11.1.7)/H2O2 oxidized the endogenous central nervous system alkaloid salsolinol (SAL) at physiological pH. The proximate oxidation product was an electrophilic ortho-quinone (4) which at pH 7.0 rapidly tautomerized. Four major initial products were formed from 4: cis- and trans-1,2,3,4-tetrahydro-1-methyl-4,6,7-isoquinolinetriol (A and B, respectively), 2,3,4-trihydro-1-methyl-7-hydroxy-6-oxyisoquinoline (C), and 1-methyl-6,7-isoquinoline diol (D). Mechanisms describing the formation of these products have been presented. Ortho-quinone 4, formed in the enzyme-mediated reactions, was rapidly attacked by glutathione to yield the 5-S-, 8-S-, and 5,8-bi-S-glutathionyl conjugates of SAL. Preliminary experiments indicated that injection of A, B and C into the CNS of mice evoked profound behavioral effects. Quinone methide C was toxic. The potential role of the oxidation of salsolinol in the neurodegenerative and behavioral effects associated with chronic alcoholism is discussed.
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PMID:Interactions of salsolinol with oxidative enzymes. 165 22

The electrochemical oxidation of the central mammalian alkaloid 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (1) has been studied in neutral aqueous solution at a pyrolytic graphite electrode (PGE). Voltammograms of 1 show two closely spaced oxidation peaks, Ia and IIa. At potentials less positive than the peak potential (Ep) for peak Ia, 1 is oxidized to a radical intermediate which dimerizes to give two diastereomers of 5,5'-bi(1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline) (5 and 6). At potentials more positive than Ep for peak Ia the putative radical intermediate is further electrooxidized to a C(5)-centered carbocation which reacts with 1 in an ion-substrate reaction to give 5 and 6 or with water to give, ultimately, 1-methyl-1,2,3,4-tetrahydro-beta-carboline-5,6-dione (12). Dimers 5 and 6 give two reversible oxidation peaks at the PGE, the second of which corresponds to peak IIa observed in voltammograms of 1. Because 5 and 6 are easily oxidizable compounds they are only observed as products in the initial stages of the controlled potential electrooxidation of 1. Tyrosinase/O2, human ceruloplasmin/O2, and peroxidase/H2O2 also oxidize 1 to 5, 6, and 12 as the initial products. In the presence of glutathione the electrochemically driven and enzyme-mediated oxidations of 1 result in the formation of 5-S-glutathionyl-1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline as a major product. Central administration of diastereomer 5 or 6 to mice evoked behavioral responses similar to those caused by the opioid analgesics. These behavioral effects, which include spatial disorientation and a characteristic ducklike walk, became most pronounced approximately 3 h after drug administration and continued for about 3 days. Neurotransmitter and related metabolite analyses of whole brain reveal that 5 and 6 cause a general increase in dopaminergic and serotonergic activity and a small but significant decrease in cholinergic activity. These transmitter/metabolite disturbances appear to parallel the time course of the observed behavioral effects. The possible roles of in vivo oxidations of 1, an alkaloid which is elevated in mammalian brain following ethanol consumption, in the addictive, behavioral, and neurodegenerative consequences of chronic alcoholism are discussed.
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PMID:Oxidation chemistry and biochemistry of the central mammalian alkaloid 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline. 173 36

Luminol chemiluminescence was observed by addition of menadione to yeast cell suspension and was amplified 1000-fold by further addition of Fe-complex. Catalase, superoxide dismutase and ceruloplasmin had inhibitory effects on luminol chemiluminescence, indicating the extracellular generation of active oxygens (H2O2 and O2-) and reduction of Fe-complex. The generation of H2O2 and reduction of Fe-complex were mainly dependent on the activity of NADH: menadione oxidoreductase in the plasma membrane and cytosol fractions. Both luminol chemiluminescence and H2O2 production were sensitive to the inhibitory effects of proton conductor, ionophorous antibiotics and ATPase inhibitor rather than the inhibitors of the mitochondria electron transport system. The incubation of glucose with yeast cells caused a parallel increase in luminol chemiluminescence, H2O2 production and intracellular NADH concentration. These facts suggest that menadione-catalyzed H2O2 production and chemiluminescence are used as the indicators of cell activity to keep the NADH concentration and NADH: menadione oxidoreductase activity which may be sensitive to the change in pH and ion concentrations.
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PMID:Extracellular generation of active oxygen species catalyzed by exogenous menadione in yeast cell suspension. 187

Peroxidase (EC 1.11.1.7)/H2O2, ceruloplasmin (human type X)/O2, and tyrosinase (EC 1.14.18.1)/O2 all oxidized the indolic neurotransmitter 5-hydroxytryptamine (5-HT) in the physiological pH domain. Peroxidase/H2O2 oxidized 5-HT at pH values down to about 2.5. All oxidation reactions generated complex mixtures of products which included at least one known neurotoxin, tryptamine-4,5-dione. In general, the enzymatic oxidation pathways paralleled the in vitro electrochemical oxidation of 5-HT which has permitted suggestions to be made concerning the probable mechanisms of the enzyme-mediated reactions.
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PMID:Interactions of 5-hydroxytryptamine with oxidative enzymes. 190 Dec 10

The neurodegenerative properties of the serotonergic neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) are widely believed to result from its autoxidation in the central nervous system. The autoxidation chemistry of 5,6-DHT has been studied in aqueous solution at pH 7.2. The reaction is initiated by direct oxidation of the indolamine by molecular oxygen with resultant formation of the corresponding o-quinone 1 and H2O2. A rapid nucleophilic attack by 5,6-DHT on 1 leads to 2,7'-bis(5,6-dihydroxytryptamine) (6) which is more rapidly autoxidized than 5,6-DHT to give the corresponding diquinone 7 along with 2 mol of H2O2. The accumulation of 6 in the reaction solution during the autoxidation of 5,6-DHT despite its more rapid autoxidation indicates that diquinone 7 chemically oxidizes 5,6-DHT (2 mol) to quinone 1 so that an autocatalytic cycle is established. The H2O2 formed as a byproduct of these autoxidation reactions can undergo Fenton chemistry catalyzed by trace transition metal ion contaminants with resultant formation of the hydroxyl radical, HO., which directly oxidizes 5,6-DHT to a radical intermediate (9a/9b). This radical is directly attacked by O2 to yield quinone 1 and superoxide radical anion, O2.-, which further facilitates Fenton chemistry by reducing, inter alia, Fe3+ to Fe2+. A minor side reaction of 1 with water leads to formation of at least two trihydroxytryptamines. Diquinone 7 ultimately reacts with 6, 5,6-DHT, and perhaps trihydroxytryptamines, leading via a sequence of coupling and oxidation reactions to a black indolic melanin polymer. Enzymes such as tyrosinase, ceruloplasmin, and peroxidase and rat brain mitochondria catalyze the oxidation of 5,6-DHT to form dimer 7 and, ultimately, indolic melanin. The role of the autoxidation and the enzyme-mediated and mitochondria-promoted oxidations of 5,6-DHT in expressing the neurodegenerative properties of the indolamine are discussed.
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PMID:Further insights into the oxidation chemistry and biochemistry of the serotonergic neurotoxin 5,6-dihydroxytryptamine. 217 37

Reduced cytochrome-c, reduced myoglobin and oxyhemoglobin respectively have been oxidized to oxidized cytochrome-c, metmyoglobin and methemoglobin by ceruloplasmin. Metmyoglobin and methemoglobin formation was stoichiometric while oxidized cytochrome-c reacted catalytically. Only 50% methemoglobin was formed which suggested that two hemes out of four could transfer electrons. Hydrogen peroxide was formed in the reaction of reduced cytochrome-c with ceruloplasmin.
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PMID:Electron transfer between heme proteins and ceruloplasmin. 253 14


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