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 susceptibility of a number of human neutrophil granule enzymes to oxidative inactivation was investigated. Addition of H2O2 to the cell-free medium from stimulated neutrophils resulted in inactivation of all enzymes tested. This was inhibited by azide and methionine, indicating that inactivation was due to myeloperoxidase-derived oxidants. Lysozyme was more than 50% inactivated by one addition of 100 nmol of H2O2/ml, whereas myeloperoxidase, beta-glucuronidase, gelatinase and collagenase were almost completely inactivated by three additions. Cathepsin G was slightly less susceptible, whereas elastase was extremely resistant to oxidative attack. Myeloperoxidase-dependent enzyme inactivation may be a means whereby the neutrophil can terminate the activity of its granule enzymes and control the release of degradative enzymes into the tissues.
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PMID:Myeloperoxidase-dependent oxidative inactivation of neutrophil neutral proteinases and microbicidal enzymes. 282 16

The instability of human myeloperoxidase [EC 1.11.1.7] compound I, which was spontaneously reduced to compound II, and the abnormal stoichiometry of the reaction of myeloperoxidase with H2O2 were investigated. As to the former, a pretreatment of myeloperoxidase with H2O2 did not stabilize compound I, and no difference in its stability was observed between native (alpha 2 beta 2) and hemi (alpha beta) myeloperoxidase. From these results, it was thought that the instability of compound I was caused by neither the presence of endogenous donors nor the intramolecular reduction of compound I to compound II by the other heme in the native enzyme molecule. As for the latter, true catalase activity of myeloperoxidase was demonstrated by monitoring O2 evolution after the injection of H2O2 into the enzyme solution. Myeloperoxidase compound I reacted with H2O2 and returned to the ferric state with concomitant evolution of an O2 molecule. Accordingly, the abnormal stoichiometry of the reaction with H2O2 and a part of the instability of compound I can probably be ascribed to this true catalase activity.
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PMID:Reaction of human myeloperoxidase with hydrogen peroxide and its true catalase activity. 282 73

Myeloperoxidase, a granule-associated enzyme of neutrophils and monocytes, combines with H2O2 and chloride to form a potent microbicidal system that contributes to phagocyte antimicrobial activity. The nature of the lesion or lesions induced by the myeloperoxidase system which are responsible for the loss of microbial replicative activity (viability) remains unknown. Using Escherichia coli grown to late log or stationary phase under conditions of low aeration with succinate as the sole carbon source, we found that myeloperoxidase-induced loss of microbial viability could be correlated with a decrease in succinate-dependent respiration (succinate oxidase activity). Succinate dehydrogenase activity fell rapidly to undetectable levels during incubation with the myeloperoxidase system, suggesting that damage to the dehydrogenase was a major factor in the loss of oxidase activity. Other components of the succinate oxidase system were resistant to the actions of myeloperoxidase. The ubiquinone-8 and cytochrome components of the respiratory chain remained nearly constant in amount despite reduction of respiration to undetectable levels. However, as expected from the loss of succinate dehydrogenase activity, succinate-ubiquinone reductase and succinate-cytochrome reductase activities were markedly impaired. We propose that the loss of E. coli viability induced by the myeloperoxidase-H2O2-chloride system is due in part to the loss of electron transport function consequent to the oxidation of critical catalytic centers in susceptible dehydrogenases.
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PMID:Myeloperoxidase-mediated damage to the succinate oxidase system of Escherichia coli. Evidence for selective inactivation of the dehydrogenase component. 282 9

Our previous study suggested that impaired bactericidal activity of polymorphonuclear leukocytes in patients with biliary atresia might be due to decrease in superoxide-generating activity and that serum factors may play an important role. In the present study, analysis of the patients' serum revealed that, among 15 bile acids, glycine or taurine conjugated chenodeoxycholic acid and cholic acid were markedly elevated. To examine the effects of bilirubin and these bile acids and conjugated lithocholic acids on the leukocyte function, we measured cytolysis, phorbol myristate acetate-induced superoxide generation, and myeloperoxidase activity, using normal human polymorphonuclear leukocytes. Bilirubin ranging from 5 to 20 mumol/L was cytolytic and more potently inhibited the superoxide generation. The inhibition by bilirubin was also observed in the presence of 10% human serum or 2.0% human serum albumin, though the cell viability was almost completely preserved. On the other hand, conjugated chenodeoxycholic acids and cholic acids, ranging from 0.5 to 1.5 mmol/L or conjugated lithocholic acids, ranging from 0.02 to 0.05 mmol/L, did not inhibit the superoxide generating activity, though the conjugated chenodeoxycholic acids and lithocholic acids did induce cytolysis. Myeloperoxidase activity was little affected, except in the case of conjugated lithocholic acids. These results suggest that in patients with biliary atresia, bilirubin, probably the unconjugated form, more than bile acids might be one of the influential factors in the suppression of bactericidal activity of polymorphonuclear leukocytes, by inhibiting the superoxide-generating activity.
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PMID:Impaired polymorphonuclear leukocyte function in biliary atresia: role of bilirubin and bile acids. 282 41

Myeloperoxidase gene transcription in isolated nuclei from HL-60 cells induced to differentiate into granulocytes by dimethyl sulfoxide or into macrophages by 12-O-tetradecanoylphorbol-13-acetate was studied by dot-blot hybridization of a myeloperoxidase cDNA to the 32P-labeled nuclear transcripts. Myeloperoxidase gene transcription, like that of c-myc gene transcription, was reduced to a low level within 12 h after the inductions of these differentiations. In contrast, transcription of the actin gene remained constant. These results indicate that decrease in myeloperoxidase synthesis in HL-60 cells during differentiation is regulated at a transcriptional level.
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PMID:Transcriptional regulation of myeloperoxidase gene expression in myeloid leukemia HL-60 cells during differentiation into granulocytes and macrophages. 283 11

DNA synthesis, morphology, specific RNA accumulation and rates of specific protein synthesis in GM-CSF stimulated bone marrow progenitor cells were studied. DNA synthesis increased markedly for 64 hours and then gradually decreased to 5% maximal activity by 160 hours. Morphologic examination 40 to 64 hours after stimulation revealed an increasing proportion of immature myeloid cells. After this proliferative peak, cells differentiated into segmented neutrophils and monocytes/macrophages; only mature forms were present by 160 hours. Accumulation of mRNA for c-myb and c-myc was maximal at 40 hours just prior to maximal [3H]thymidine incorporation, while maximal accumulation of histone type 3 (H3) was coincident with maximal [3H]thymidine incorporation at 64 hours. As proliferation decreased and differentiation proceeded, levels of mRNA for c-myb and H3 decreased markedly, while levels of RNA for c-myc decreased gradually and remained elevated above day 0 levels. Levels of c-fos mRNA fluctuated slightly during the first 64 hours of culture and increased 13-fold by 160 hours when mature cells were present. Similarly, beta-2 microglobulin mRNA increased steadily to maximal levels at 112 to 160 hours which were 15-fold higher than day 0 levels. Myeloperoxidase (MPO) mRNA was present in maximal amounts at 40 to 64 hours after stimulation with GM-CSF as the number of immature myeloid cells peaked. Immunoprecipitation of MPO from pulse-labeled cell lysates demonstrated a 7-fold rise in synthetic rate of MPO of 64 hours and a 28-fold decline by 160 hours when only 5% immature myeloid cells were present. Thus, MPO protein synthesis closely follows MPO mRNA accumulation. Immunoprecipitation of lactoferrin, a marker of myeloid secondary granules, demonstrated a gradual 5-fold increase in synthetic rate as the cells matured. Taken together, these data show that maximal expression of the early myeloid differentiation enzyme myeloperoxidase in GM-CSF stimulated normal bone marrow cells occurs during peak proliferation of immature myeloid cells.
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PMID:Myeloperoxidase and oncogene expression in GM-CSF induced bone marrow differentiation. 283 25

Myeloperoxidase and eosinophil peroxidase were isolated from the bone marrow cells of rats treated with or without propylthiouracil (PTU) which caused bone marrow depression. PTU treatment decreased the activity of myeloperoxidase but not of eosinophil peroxidase using guaiacol as the electron donor. However, when KI,N-N'-dimethyl-p-phenylenediamine and pyrogallol were used as the electron donor, the activity of only eosinophil peroxidase was inhibited by PTU treatment. EPR spectra indicated that the structure of myeloperoxidase surrounding the heme iron changed from a rhombic form into an axial one by the repeated administration of PTU. Therefore, the inactivation of peroxidases by PTU treatment was accompanied by an alteration of their structures surrounding the heme.
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PMID:Inactivation of peroxidases of rat bone marrow by repeated administration of propylthiouracil is accompanied by a change in the heme structure. 283 28

We have previously demonstrated the ability of human neutrophil myeloperoxidase to bind to cell wall mannan polysaccharide isolated from Candida albicans. This binding capacity provides for association of the enzyme with target yeast which is essential for efficient candidacidal activity. In this report, we further consider the role of the mannan-binding property of myeloperoxidase in the candidacidal activity of the enzyme. Solubilized mannan antagonizes binding of the enzyme to yeast, suggesting that mannan may be a primary component of the fungal cell wall which serves as a target for binding of myeloperoxidase. Myeloperoxidase is shown to form complexes with both solubilized mannan and Candida yeast, with Kds of 0.97 x 10(-5) M and 1.2 x 10(-5) M, respectively. The interaction between myeloperoxidase and mannan does not allow the enzyme to readily dissociate from the surface of target yeast. As a result, the enzyme may be unable to dissociate from dead yeast to become available for binding to additional fungal targets.
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PMID:Candidacidal activity of myeloperoxidase: characterization of myeloperoxidase-yeast complex formation. 284 Sep 7

Myeloperoxidase catalyses the conversion of H2O2 and Cl- to hypochlorous acid (HOCl). It also reacts with O2- to form the oxy adduct (compound III). To determine how O2- affects the formation of HOCl, chlorination of monochlorodimedon by myeloperoxidase was investigated using xanthine oxidase and hypoxanthine as a source of O2- and H2O2. Myeloperoxidase was mostly converted to compound III, and H2O2 was essential for chlorination. At pH 5.4, superoxide dismutase (SOD) enhanced chlorination and prevented formation of compound III. However, at pH 7.8, SOD inhibited chlorination and promoted formation of the ferrous peroxide adduct (compound II) instead of compound III. We present spectral evidence for a direct reaction between compound III and H2O2 to form compound II, and for the reduction of compound II by O2- to regenerate native myeloperoxidase. These reactions enable compound III and compound II to participate in the chlorination reaction. Myeloperoxidase catalytically inhibited O2- -dependent reduction of Nitro Blue Tetrazolium. This inhibition is explained by myeloperoxidase undergoing a cycle of reactions with O2-, H2O2 and O2-, with compounds III and II as intermediates, i.e., by myeloperoxidase acting as a combined SOD/catalase enzyme. By preventing the accumulation of inactive compound II, O2- enhances the activity of myeloperoxidase. We propose that, under physiological conditions, this optimizes the production of HOCl and may potentiate oxidant damage by stimulated neutrophils.
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PMID:Superoxide modulates the activity of myeloperoxidase and optimizes the production of hypochlorous acid. 284 72

Myeloperoxidase compound II has been characterized by using optical absorption and resonance Raman spectroscopies. Compared to compounds II in other peroxidases, the electronic and vibrational properties of this intermediate are strongly perturbed due to the unusual active-site iron chromophore that occurs in myeloperoxidase. Despite this difference in prosthetic group, however, other properties of myeloperoxidase compound II are similar to those observed for this intermediate in the more common peroxidases (horseradish peroxidase in particular). Two forms of the myeloperoxidase intermediate species, each with distinct absorption spectra, are recognized as a function of pH. We present evidence consistent with interconversion of these two forms via a heme-linked ionization of a distal amino acid residue with a pKa congruent to 9. From resonance Raman studies of isotopically labeled species at pH 10.7, we identify an iron-oxygen stretching frequency at 782 cm-1, indicating the presence of an oxoferryl (O = FeIV) group in myeloperoxidase compound II. We further conclude that the oxo ligand is not hydrogen bonded above the pKa but possibly exhibits oxygen exchange with the medium at pH values below the pKa due to hydrogen bonding of the oxo ligand to the distal protein group.
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PMID:Identification and properties of an oxoferryl structure in myeloperoxidase compound II. 284 34


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