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:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neutrophil myeloperoxidase-H2O2-halide enzyme system produces hypochlorous acid and chlorinated amine compounds capable of killing a variety of target cells. In the present study we hypothesized that the myeloperoxidase enzyme system is one mechanism for airway epithelial damage in patients with cystic fibrosis (CF). Enzyme linked immunosorbent assay detected high antigenic levels of myeloperoxidase in sputum samples of seven patients with CF. Myeloperoxidase was purified to homogeneity from CF sputum and from blood neutrophils by a three-step technique involving dialysis, gel filtration, and ion-exchange chromatography. CF sputum myeloperoxidase and neutrophil myeloperoxidase appeared identical by acid gel electrophoresis and Ouchterlony experiments. CF sputum myeloperoxidase also contained approximately the same enzymatic activity as neutrophil myeloperoxidase. The myeloperoxidase enzyme system was tested for its cytotoxic potential in a tracheal ring culture system. Myeloperoxidase-induced cytotoxicity for airway epithelium was confirmed by light microscopy and radiolabelling experiments. These findings suggest a possible role for neutrophil myeloperoxidase in CF lung disease.
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PMID:Purification and cytotoxic potential of myeloperoxidase in cystic fibrosis sputum. 284 83

The changes in the oxidation state of the leucocyte enzyme myeloperoxidase, induced by buffer and thiols, were studied with visible-light-absorption spectroscopy. It was concluded that phosphate buffer contains small amounts of H2O2 and that thiols, when added to buffer, induce the generation of minute amounts of superoxide radical anion. These minute amounts of reduced oxygen species are suggested to account for the initiation of myeloperoxidase-oxidase oxidation of thiols. Myeloperoxidase was found to be in its Compound III oxidation state during myeloperoxidase-oxidase oxidation of thiols. However, myeloperoxidase-mediated oxidation of thiols with concomitant O2 consumption can also occur with myeloperoxidase in its Compound II oxidation state. These studies indicate that the ferro and Compound III oxidation states may not be essential intermediates in myeloperoxidase-oxidase oxidation of thiols, but rather that the formation of the Compound III oxidation state retards the reaction.
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PMID:Myeloperoxidase oxidation states involved in myeloperoxidase-oxidase oxidation of thiols. 285 3

Myeloperoxidase was found to promote peroxidation of phospholipids under acidic conditions in the presence of hydrogen peroxide and iodide ions. The peroxidation was markedly enhanced by pyrophosphate-chelated ferric iron and was inhibited by desferrioxamine and superoxide dismutase. This observation adds lipid peroxidation to the oxidative damage caused by myeloperoxidase, which is a phagocytic cell enzyme involved in phagocyte-mediated cell destruction.
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PMID:Peroxidation of phospholipids promoted by myeloperoxidase. 285 26

Myeloperoxidase, H2O2, and a halide (chloride, bromide, or iodide) form a potent microbicidal system that contributes to the antimicrobial activity of neutrophils. The mechanism of toxicity is not completely understood. Powerful oxidants are formed that presumably attack the microbe at a variety of sites. Among the consequences of this attack is the release of a large proportion of 59Fe of prelabeled organisms. We report here that the myeloperoxidase-H2O2-halide system oxidizes the iron-sulfur centers of model compounds (spinach ferredoxin) and intact microorganisms (Escherichia coli) with the loss of labile sulfide. The oxidation of the iron-sulfur centers of ferredoxin was measured by the fall in absorbance at 420 nm (bleaching) and by the loss of 5,5'-dithiobis-(2-nitrobenzoic acid) reducing activity. The latter compound is a sulfhydryl reagent that is reduced by ferredoxin labile sulfide during denaturation. The oxidation of E. coli iron-sulfur centers by the peroxidase system was determined by the loss of labile sulfide content, as measured by the release of H2S by acid and its reaction with zinc acetate to form ZnS. The halides were effective as components of the peroxidase system in the order I greater than Br greater than Cl. The oxidation of E. coli iron-sulfur centers by the peroxidase system was rapid and preceded the loss of viability. Gentamicin, at a concentration which produced a loss of viability comparable to that of the peroxidase system, did not cause a loss of labile sulfide from E. coli, suggesting that labile sulfide loss is not a nonspecific reflection of the loss of viability, but a direct consequence of the action of the myeloperoxidase system. The oxidation of iron-sulfur centers in microorganisms by the myeloperoxidase-H2O2-halide system may contribute to the death of the organism.
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PMID:Oxidation of microbial iron-sulfur centers by the myeloperoxidase-H2O2-halide antimicrobial system. 298 37

Addition of the tumor promoter phorbol myristate acetate to polymorphonuclear leukocytes results in the oxidation of the arylamine carcinogens; [14C]benzidine, N-[14C]methylaminoazobenzene and [14C]aminofluorene to reactive intermediate(s) that bind irreversibly to the leukocyte DNA. The binding was dependent on oxygen and was decreased by sulfhydryl inhibitors and phenolic antioxidants that inhibit the respiratory burst triggered by the phorbol myristate. Both the binding and the respiratory burst were increased by azide, presumably as a result of intracellular catalase inhibition. However higher concentrations of azide and cyanide prevented binding without affecting the respiratory burst indicating that myeloperoxidase is a catalyst for the binding. Granules isolated from the activated leukocytes and H2O2 catalyzed a cyanide sensitive benzidine binding to calf thymus DNA. Myeloperoxidase and H2O2 also catalysed extensive binding of these arylamines to calf thymus DNA. The leukocytes appear to be a useful model cell for studying one electron oxidation-catalyzed carcinogen activation.
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PMID:Peroxidase-mediated irreversible binding of arylamine carcinogens to DNA in intact polymorphonuclear leukocytes activated by a tumor promoter. 298 60

Myeloperoxidase was purified from human polymorphonuclear leukocytes and the effect of chloride upon the EPR and potentiometric properties was studied. The redox titration between the ferrous and ferric states of the enzyme yielded n = 1 Nernst plots between pH 9 and 4, with clear isosbestic points in the optical spectra during the redox change. The midpoint potential (Em) between the ferric and ferrous forms of the enzyme exhibited a pH-dependent change between pH 4 and 9, and the effect of added chloride ion indicated that Cl- competed with OH- for a binding site on the enzyme. Interestingly, the pH dependence of the Em indicated that the overall redox reactions of the enzyme was: ferric myeloperoxidase + 2e- + 1H+ = ferrous myeloperoxidase. Myeloperoxidase exhibited a rhombic high spin EPR signal which exhibited reduced rhombicity upon the binding of chloride. Our results strongly suggest that chloride binds to the sixth coordination position of the chlorin iron in myeloperoxidase by replacing the water which is the sixth ligand in the resting state. It is also concluded that the two iron centers are identical and that there is no interaction between them.
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PMID:The effect of chloride on the redox and EPR properties of myeloperoxidase. 298 85

Human alpha 1-proteinase inhibitor is easily susceptible to inactivation because of the presence of a methionyl residue at its reactive site. Thus, oxidizing species derived from the myeloperoxidase system (enzyme, H2O2, and C1-), as well as hypochlorous acid, can inactivate this inhibitor, although H2O2 alone has no effect. Butylated hydroxytoluene, a radical scavenger, partially protects alpha 1-proteinase inhibitor from the myeloperoxidase system and completely protects it from hypochlorous acid. Each oxidant also reacts differently with the inhibitor, in that the myeloperoxidase system and hypochlorous acid can each oxidize as many as six methionyl residues, but hypochlorous acid can also oxidize a single tyrosine residue. Myeloperoxidase can be inactivated by hypochlorous acid, by autoxidation in the presence of H2O2 and C1-, as well as by H2O2 alone. Butylated hydroxytoluene completely protects this enzyme from hypochlorous acid inactivation, does not affect the action of H2O2, and enhances autoinactivation. As many as six methionyl residues and two tyrosine residues could be oxidized during autoxidation and six methionine residues by H2O2 alone. Eight methionine residues and one tyrosine residue could be oxidized by hypochlorous acid. The tyrosine residue in myeloperoxidase was oxidized only at a relatively high concentration (600 microM) of hypochlorous acid at which point the enzyme simultaneously and completely lost its enzymatic activity. Loss of activity of myeloperoxidase could also be correlated with the loss of the heme groups present in the enzyme when a relatively high concentration of hypochlorous acid (600 microM) was used and also during autoxidation. It appears that once there is sufficient oxidant to modify one of the tyrosine residues, the heme group itself becomes susceptible.
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PMID:Differential effects of oxidizing agents on human plasma alpha 1-proteinase inhibitor and human neutrophil myeloperoxidase. 299 May 44

Cigarette smokers have an increased risk of chronic obstructive airways disease which has been attributed to a protease-antiprotease imbalance in the lung. The neutrophil is an important source of proteases as well as of myeloperoxidase, which oxidatively inactivates alpha-1-proteinase inhibitor (alpha-1-PI). The purpose of this study is to evaluate the protease-antiprotease imbalance hypothesis by measuring changes in peripheral blood components in a group of 110 young, male, asymptomatic smokers and an equal number of age-matched non-smokers. Significant (p = 0.001), but modest impairment of pulmonary function was observed in the smokers as measured by both forced expiratory spirometry and the single breath nitrogen test. A 35% increase (p = 0.0001) in peripheral blood leukocytes in smokers was attributable to increases in neutrophils (44%), lymphocytes (31%) and monocytes (23%). This increase in leukocyte count correlated significantly (p less than or equal to 0.01) with some of the more sensitive indicators of airway obstruction (FEV1/FVC, CV/VC, CC/TLC, and delta N2/L). Myeloperoxidase activity of neutrophils isolated from peripheral blood of smokers was 13% higher than in non-smokers, while elastase activity per neutrophil was apparently unaffected by smoking. In 50 subject pairs, elevations in serum alpha-1-PI concentrations in smokers (13.7%) were comparable to similar increases in trypsin (9.9%) and elastase (12.4%) inhibitory capacities. Expressed as nanomoles protease inhibited per nanomole of alpha-1-PI, the apparent functional activity of alpha-1-PI was unaltered by smoking. However, a lower, apparent functional activity of alpha-1-PI against trypsin and elastase was observed in both smokers and non-smokers with higher serum alpha-1-PI concentrations. Thus, in a population of young smokers, changes in leukocyte count, neutrophil lysosomal enzyme activities, and functional serum antiprotease activity appear to be consistent with the establishment of a protease-antiprotease imbalance. This imbalance may predispose these smokers to obstructive lung disease.
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PMID:Effect of smoking on peripheral blood leukocytes and serum antiproteases. 299 5

The first high resolution proton nuclear magnetic resonance spectra are reported for the native ferric and ferric cyano complexes of bovine lactoperoxidase. The spectrum of the native species exhibits broad heme signals in a far downfield region characteristic of the high-spin ferric state. The low-spin cyano complex yields a proton nuclear magnetic resonance spectrum with signals as far as 68.5 ppm downfield and as far as -28 ppm upfield of the tetramethylsilane reference. These peak positions are anomalous with respect to those seen only as far as 35 ppm downfield in other cyano hemoprotein complexes. An extreme asymmetry in the unpaired spin delocalization pattern of the iron porphyrin is suggested. The unusual proton nuclear magnetic resonance properties parallel distinctive optical spectral properties and the exceptional resistance to heme displacement from the enzyme. Lactoperoxidase utilized in these studies was isolated from raw milk and purified by an improved, rapid chromatographic procedure.
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PMID:High resolution proton nuclear magnetic resonance spectroscopy of lactoperoxidase. 300 59

Myeloperoxidase, stored in azurophil granules of neutrophils, is synthesized in promyelocytes as a larger molecular weight precursor, which is processed to yield a transient Mr 82 000 intermediate and mature polypeptides with molecular weights of 62 000 and 12 000. We have tried to define subcellular sites for processing using metabolic labelling of the promyelocytic leukemia cell line HL-60 in combination with subcellular fractionation on a Percoll gradient. A reasonable separation was achieved between azurophil granules, Golgi elements and endoplasmic reticulum. The finding of almost exclusively fully processed myeloperoxidase in granules and a mixture of unprocessed and processed polypeptide in fractions enriched in Golgi elements suggests that processing occurred mainly in pregranular structures. Monensin, which exchanges protons for Na+, and the base chloroquine blocked processing probably by inhibition of transport through the Golgi apparatus. However, the lysosomotropic NH4+ cation did not inhibit processing or transport indicating that processing is not necessarily influenced by pH-dependent mechanisms. Results from digestion with endoglycosidase H, incubation with tunicamycin and metabolic labelling with [3H]mannose indicated that myeloperoxidase contained high mannose oligosaccharide side chains. Also [32P]phosphate incorporated into Mr 90 000 and Mr 62 000 myeloperoxidase was susceptible to endoglycosidase H indicating that oligosaccharide side chains are modified by phosphorylation as in lysosomal enzymes. Thus, even if myeloperoxidase contained mannose 6-phosphate residues, these may not necessarily be involved in directing transport to the azurophil granules.
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PMID:The processing and intracellular transport of myeloperoxidase. Modulation by lysosomotropic agents and monensin. 300 51


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