Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenous respiration of the parasitic nematode Nippostrongylus brasiliensis and the succinate oxidase activity of isolated mitochondria were partially inhibited by antimycin A; the remaining respiratory activity was sensitive to salicylhydroxamic acid (SHAM). Sub-millimolar concentrations of SHAM markedly stimulated respiration by 60% in whole N. brasiliensis and isolated mitochondria; stimulation by SHAM was not observed in the presence of antimycin A. Little change in the relative fluxes of electrons through the classical, antimycin A-sensitive pathway and the alternative SHAM sensitive pathway was observed between low and high O2 concentrations; this may suggest that the O2 affinities of both pathways are similar. O2 dependence of respiration showed O2 thresholds above which respiration decreases; in the absence of inhibitors whole N. brasiliensis and isolated mitochondria had threshold values around 60 microM O2. Increased O2 threshold values were observed in the presence of SHAM and antimycin A. The apparent Km values for O2 of whole N. brasiliensis and isolated mitochondria were 31 +/- 2 microM O2 and 3.5 +/- 0.2 microM O2 respectively; this difference in apparent Km values may reflect the presence of O2 gradients in the whole worm. The Km and O2 inhibition threshold values observed for whole N. brasiliensis are in good agreement with the proposed range of O2 concentrations thought to exist within the worm's natural environment. H2O2 production was detected in respiring uncoupled mitochondria, but H2O2 could not be detected in the medium surrounding whole N. brasiliensis. SHAM-stimulated respiration was accompanied by increased H2O2 production which was prevented by the addition of antimycin A.
Mol Biochem Parasitol 1987 Jan 15
PMID:Effects of inhibitors on the oxygen kinetics of Nippostrongylus brasiliensis. 357 44

Addition of vanadate, stimulated oxidation of NADH by rat liver microsomes. The products were NAD+ and H2O2. High rates of this reaction were obtained in the presence of phosphate buffer and at low pH values. The yellow-orange colored polymeric form of vanadate appears to be the active species and both ortho- and meta-vanadate gave poor activities even at mM concentrations. The activity as measured by oxygen uptake was inhibited by cyanide, EDTA, mannitol, histidine, ascorbate, noradrenaline, adriamycin, cytochrome c, Mn2+, superoxide dismutase, horseradish peroxidase and catalase. Mitochondrial outer membranes possess a similar activity of vanadate-stimulated NADH oxidation. But addition of mitochondria and some of its derivative particles abolished the microsomal activity. In the absence of oxygen, disappearance of NADH measured by decrease in absorbance at 340 nm continued at nearly the same rate since vanadate served as an electron acceptor in the microsomal system. Addition of excess catalase or SOD abolished the oxygen uptake while retaining significant rates of NADH disappearance indicating that the two activities are delinked. A mechanism is proposed wherein oxygen receives the first electron from NAD radical generated by oxidation of NADH by phosphovanadate and the consequent reduced species of vanadate (Viv) gives the second electron to superoxide to reduce it H2O2. This is applicable to all membranes whereas microsomes have the additional capability of reducing vanadate.
Mol Cell Biochem 1987 Jun
PMID:Vanadate-stimulated NADH oxidation in microsomes. 365 Jun 94

Contrary to previous reports in the literature, bloodstream forms of the haemoflagellate protozoan Trypanosoma brucei brucei are not deficient in their ability to metabolize hydrogen peroxide, although they either lack or only possess the normal enzymes for H2O2 detoxification, catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1.11.1.9), at extremely low levels. The hydrogen peroxide which is consumed appears to be reduced by NADPH derived from glucose via the pentose phosphate pathway. This process requires the newly discovered cofactor trypanothione.
Mol Biochem Parasitol 1986 Aug
PMID:Hydrogen peroxide metabolism in Trypanosoma brucei. 374 70

Substrate activity of a flavin-containing monooxygenase isolated from rabbit lung microsomes has been examined with a number of primary, secondary, and tertiary amines. Of the secondary and tertiary amines tested, trifluoperazine, prochlorperazine, N, N-dimethyloctylamine, desmethylperazine, and N-methyloctylamine half-saturate the enzyme at concentrations less than 100 microM. Although the lung enzyme does not exhibit detectable substrate activity with primary arylamines, it catalyzes N-oxygenation of alkylamines to oximes. Studies on the mechanism for the oxidation of n-dodecylamine suggest that the amine is first oxidized to the hydroxylamine which is then further oxidized to the oxime. This interpretation is based on product identification, kinetic studies, and changes in the ratio of hydroxylamine to oxime formed as a function of initial substrate concentration. Kinetic constants calculated for the oxidation of n-dodecylamine and n-dodecylhydroxylamine indicate that the latter saturates the enzyme at a 100-fold lower concentration than that required for the parent amine, and the hydroxylamine is the dominant product only at saturating concentrations of the amine. The ratio of substrate-dependent NADPH and O2 consumption and product formation (hydroxylamine + 2 X oxime) is approximately 1.0:0.9:0.7. Although the reason for the less than stoichiometric yield of products is not known, uncoupling of the enzyme by primary amines does not appear to be a major factor since substrate-dependent increase in H2O2 formation is never more than 3% of substrate-dependent O2 consumption.
Mol Pharmacol 1986 Dec
PMID:Substrate specificity of the rabbit lung flavin-containing monooxygenase for amines: oxidation products of primary alkylamines. 378 45

Phenylbutazone (PB), a nonsteroidal anti-inflammatory drug, is an efficient reducing cofactor for the peroxidase activity of prostaglandin H synthase (PHS). Most reducing cofactors for the peroxidase protect PHS and prostacyclin synthase from inactivation by hydroperoxides. PB, however, does not protect these enzymes, but rather augments their hydroperoxide-dependent inactivation. Using ram seminal vesicle microsomes as a source of PHS and prostacyclin synthase, we have examined the interaction of PB and exogenous hydroperoxides. Chromatographic analysis of the metabolism of 14C-labeled arachidonic acid in this system revealed that PB-dependent inactivation of PHS is markedly increased in the presence of 100 microM H2O2. This inactivation is a linear function of PB concentration between 10 and 250 microM, with a half-maximal effect in this range at about 100 microM PB. Prostacyclin synthase is even more sensitive to inactivation by the combined PB and H2O2 treatment, with a corresponding half-maximal effect at PB concentrations near 25 microM. This PB- and H2O2-dependent inactivation is demonstrable whether PGH2 is generated in situ from arachidonic acid or is added exogenously, supporting a direct effect of the treatment on prostacyclin synthase. As PB undergoes peroxide-dependent co-oxygenation catalyzed by PHS, we propose that it is an oxygenated derivative of PB, rather than the parent compound, which is responsible for the inactivation of PHS and prostacyclin synthase. Nafazatrom, a competitive inhibitor of PB co-oxygenation, blocks the effects of the PB and H2O2 treatment, supporting our proposal.
Mol Pharmacol 1985 Jan
PMID:Inactivation of prostaglandin H synthase and prostacyclin synthase by phenylbutazone. Requirement for peroxidative metabolism. 391 45

In thyroid gland, iodination takes place on the apical plasma membrane and requires the presence of the thyroid peroxidase and H2O2 generating system. H2O2 generation and NBT (nitro blue tetrazolium) reductase activity (both of which are NADPH-dependent) as well as peroxidase activity were compared for their respective orientations in membrane vesicles. The possible role of NADPH-NBT reductase activity in H2O2 generation was also examined. Results favor the conclusion that thyroid peroxidase is oriented towards the luminal side of the vesicles, whereas the NADPH site of NADPH oxidase-dependent H2O2 generation is located on the external side of the same or of different vesicles. Furthermore, it is shown that different NADPH-NBT reductase activities are present on both the outer and inner surfaces of the membrane vesicles, and that none of these activities is able to produce either H2O2 or O-2. The idea that a multi-component complex is involved in H2O2 generation is discussed, and a model is proposed which takes into account the possible spatial separation of the thyroid peroxidase site from the NADPH site of this H2O2 generation system on the apical membrane of the thyrocyte.
Mol Cell Endocrinol 1985 Jul
PMID:Relation between thyroid peroxidase, H2O2 generating system and NADPH-dependent reductase activities in thyroid particulate fractions. 401 97

Oxidation of NADH by rat erythrocyte plasma membrane was stimulated by about 50-fold on addition of decavanadate, but not other forms of vanadate like orthovanadate, metavanadate aad vanadyl sulphate. The vanadate-stimulated activity was observed only in phosphate buffer while other buffers like Tris, acetate, borate and Hepes were ineffective. Oxygen was consumed during the oxidation of NADH and the products were found to be NAD+ and hydrogen peroxide. The reaction had a stoichiometry of one mole of oxygen consumption and one mole of H2O2 production for every mole of NADH that was oxidized. Superoxide dismutase and manganous inhibited the activity indicating the involvement of superoxide anions. Electron spin resonance in the presence of a spin trap, 5, 5'-dimethyl pyrroline N-oxide, indicated the presence of superoxide radicals. Electron spin resonance studies also showed the appearance of VIV species by reduction of VV of decavanadate indicating thereby participation of vanadate in the redox reaction. Under the conditions of the assay, vanadate did not stimulate lipid peroxidation in erythrocyte membranes. Extracts from lipid-free preparations of the erythrocyte membrane showed full activity. This ruled out the possibility of oxygen uptake through lipid peroxidation. The vanadate-stimulated NADH oxidation activity could be partially solubilized by treating erythrocyte membranes either with Triton X-100 or sodium cholate. Partially purified enzyme obtained by extraction with cholate and fractionation by ammonium sulphate and DEAE-Sephadex was found to be unstable.
Mol Cell Biochem 1984 Jun
PMID:A vanadate-stimulated NADH oxidase in erythrocyte membrane generates hydrogen peroxide. 608 22

To explore the susceptibility of the extracellular protozoan, Entamoeba histolytica, to toxic oxygen intermediates, trophozoites were exposed to fluxes of O2, H2O2, and OH. generated enzymatically by the glucose oxidase and xanthine oxidase reactions. HM-1 trophozoites were resistant to O2, but were readily killed by H2O2 alone. OH. and 1O2 were not required for effective amebicidal activity. The addition of peroxidase and halide enhanced trophozoite killing by H2O2. Sonicates of amebae contained virtually no catalase and little glutathione peroxidase activity which may contribute to susceptibility to H2O2. Coupled with our previous studies with Toxoplasma gondii and Leishmania spp. these observations indicate that there is a broad spectrum of susceptibility of intra- and extracellular pathogenic protozoa to killing by oxygen intermediates.
Mol Biochem Parasitol 1981 Oct
PMID:Susceptibility of Entamoeba histolytica to oxygen intermediates. 627 8

Polymorphonuclear leukocytes (PMN) or neutrophils have multiple systems available for killing ingested bacteria. Nearly each of these incorporates H2O2 indicating the essential nature of this reactive oxygen intermediate for microbicidal activity. Following ingestion of bacteria by PMN, H2O2 is formed by the respiratory burst which consumes O2 and generates H2O2 from O2 .-. H2O2 is deposited intracellularly near bacteria within phagocytic vacuoles where it can react with the MPO-H2O2-halide system to form toxic hyperchlorous acid (HOCl) and/or possibly singlet oxygen (1O2). H2O2 can also react with O2 .- and/or iron (Fe++) from lactoferrin or bacteria to form the highly toxic hydroxyl radical (.OH). These mechanisms appear important since deficiencies of H2O2 production, myeloperoxidase or lactoferrin frequently increases their owner's susceptibility to infection. In particular, examination of PMN from infection prone patients with chronic granulomatous disease (CGD) most clearly demonstrates the importance of H2O2 in killing of bacteria. CGD PMN lack the capacity to effectively generate H2O2 and subsequently have impaired ability to kill catalase positive (H2O2 producing) but not catalase negative (not H2O2 producing) bacteria. PMN also have catalase and glutathione peroxidase systems in their cytoplasms to protect themselves from the toxicity of H2O2. Finally, while H2O2 is critical for host defense, it can also be released extracellularly and thereby play a significant role in PMN mediated tissue injury.
Mol Cell Biochem 1982 Dec 10
PMID:Hydrogen peroxide mediated killing of bacteria. 629 93

The oxidation of benzidine, a carcinogenic aromatic amine, by H2O2 is catalyzed by horseradish peroxidase or lactoperoxidase. The resulting cation free radical is moderately stable at pH 5.0, and was identified by electron spin resonance spectroscopy. Two-electron oxidation yields the benzidine di-imine. This species reacts with phenol or catechol derivatives to give colored adducts. Monoacetylbenzidine is a relatively poor peroxidase substrate, and the biological implications of this difference are discussed.
Mol Pharmacol 1983 May
PMID:An electron spin resonance study of the activation of benzidine by peroxidases. 630 34


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