A Kinetic Analysis of the Catalase Activity of Myeloperoxidase

Kettle, Anthony J.; Winterbourn, Christine C.

doi:10.1021/bi010940b

Cited by 89 publications

(70 citation statements)

References 42 publications

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“…In the absence of other available substrates, heme peroxidases can exhibit a pseudo-catalase activity, where H 2 O 2 is converted into O 2 (54,55). Using an O 2 -electrode, we found that in contrast to catalase, addition of H 2 O 2 to rIDO did not result in a net increase in O 2 levels (Fig.…”

Section: Resultsmentioning

confidence: 81%

Human Indoleamine 2,3-Dioxygenase Is a Catalyst of Physiological Heme Peroxidase Reactions

Freewan

Rees

Plaza

et al. 2013

Journal of Biological Chemistry

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Background: Certain heme proteins exhibit a pseudo-peroxidase activity that alters their function. Results: H 2 O 2 engages the peroxidase activity of indoleamine 2,3-dioxygenase (IDO) to oxidatively inactivate its dioxygenase activity, consume nitric oxide, and promote IDO protein nitration. Conclusion: IDO is a catalyst of physiological peroxidase reactions. Significance: IDO peroxidase activity has novel implications for the control and biological actions of this important immune regulatory enzyme.

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Section: Resultsmentioning

confidence: 81%

Human Indoleamine 2,3-Dioxygenase Is a Catalyst of Physiological Heme Peroxidase Reactions

Freewan

Rees

Plaza

et al. 2013

Journal of Biological Chemistry

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“…Catalase activity of the five Aspergillus strains was determined using Aspergillus niger catalase (Sigma Aldrich) as a standard, the difference in absorbance ( A 240 ) per unit time being a measure of the catalase activity [21]. Elastase activity was quantified using the elastase-specific substrate N-succinylalanyl-alany-prolyl-leucine p-nitroanilide (Sigma Aldrich) [22].…”

Section: Characterisation Of Aspergillus Strainsmentioning

confidence: 99%

Correlation between Gliotoxin Production and Virulence of Aspergillus fumigatus in Galleria mellonella

et al. 2004

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Aspergillus fumigatus is a pathogenic fungus capable of causing both allergic lung disease and invasive aspergillosis, a serious, life-threatening condition in neutropenic patients. Aspergilli express an array of mycotoxins and enzymes which may facilitate fungal colonisation of host tissue. In this study we investigated the possibility of using the insect, Galleria mellonella, for in vivo pathogenicity testing of Aspergillus species. Four clinical isolates of Aspergillus fumigatus and a single strain of Aspergillus niger were characterised for catalase and elastase activity and for the production of gliotoxin. Gliotoxin is an immunosuppressive agent previously implicated in assisting tissue penetration. Results illustrated a strain dependent difference in elastase activity but no significant difference in catalase activity. Gliotoxin production was detected in vitro and in vivo by Reversed Phase-High Performance Liquid Chromatography, with highest amounts being produced by A. fumigatus ATCC 26933 (350 ng/mg hyphae). Survival probability plots (Kaplan-Meier) of experimental groups infected with Aspergillus conidia indicate that G. mellonella is more susceptible to fungal infection by A. fumigatus ATCC 26933, implicating a critical role for gliotoxin production rather than growth rate or enzymatic activity in the virulence of A. fumigatus in this model.

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“…This reaction prevents accumulation of compound II and the associated inhibition of hypochlorous acid production (18,19). Similarly, reduction of compound II by superoxide boosts the catalytic activity of myeloperoxidase (20). …”

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confidence: 99%

Superoxide-dependent Oxidation of Melatonin by Myeloperoxidase

Ximenes

Silva

Rodrigues

et al. 2005

Journal of Biological Chemistry

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Myeloperoxidase uses hydrogen peroxide to oxidize numerous substrates to hypohalous acids or reactive free radicals. Here we show that neutrophils oxidize melatonin to N 1 -acetyl-N 2 -formyl-5-methoxykynuramine (AFMK) in a reaction that is catalyzed by myeloperoxidase. Production of AFMK was highly dependent on superoxide but not hydrogen peroxide. It did not require hypochlorous acid, singlet oxygen, or hydroxyl radical. Purified myeloperoxidase and a superoxide-generating system oxidized melatonin to AFMK and a dimer. The dimer would result from coupling of melatonin radicals. Oxidation of melatonin was partially inhibited by catalase or superoxide dismutase. Formation of AFMK was almost completely eliminated by superoxide dismutase but weakly inhibited by catalase. In contrast, production of melatonin dimer was enhanced by superoxide dismutase and blocked by catalase. We propose that myeloperoxidase uses superoxide to oxidize melatonin by two distinct pathways. One pathway involves the classical peroxidation mechanism in which hydrogen peroxide is used to oxidize melatonin to radicals. Superoxide adds to these radicals to form an unstable peroxide that decays to AFMK. In the other pathway, myeloperoxidase uses superoxide to insert dioxygen into melatonin to form AFMK. This novel activity expands the types of oxidative reactions myeloperoxidase can catalyze. It should be relevant to the way neutrophils use superoxide to kill bacteria and how they metabolize xenobiotics.Catalysis of hypochlorous acid production is the accepted physiological function of myeloperoxidase (MPO) 2 (1, 2). This heme enzyme is the major protein in neutrophils and is also present in monocytes, macrophages, microglia (3), and neurons (4, 5). It reacts with hydrogen peroxide to form the redox intermediate compound I, which oxidizes chloride to hypochlorous acid with coincident regeneration of the native enzyme (Reactions 1 and 2). HOCl indicates hypochlorous acid.Myeloperoxidase also promotes the oxidation of numerous substrates (RH) to free radical intermediates via the classical peroxidase cycle involving compound I and compound II (Reactions 3 and 4).Klebanoff (6) was the first to show that myeloperoxidase has potent antimicrobial activity because of its ability to generate hypochlorous acid. He proposed that myeloperoxidase produces hypochlorous acid inside phagosomes where it reacts with and kills ingested bacteria. However, during microbial killing myeloperoxidase functions in the presence of a high flux of superoxide (7). Superoxide reacts rapidly with native enzyme to produce oxymyeloperoxidase or compound III (Reaction 5; k 5 ϭ 2 ϫ 10 6 M Ϫ1 s Ϫ1 (8)), which is the dominant form of myeloperoxidase in stimulated neutrophils (9). Reactions of superoxide with myeloperoxidase are likely to be important in host defense because it has been demonstrated that superoxide enhances myeloperoxidasedependent killing of Staphylococcus aureus by isolated human neutrophils (10). The nature of this interaction has yet to be revealed.Compound II...

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A Kinetic Analysis of the Catalase Activity of Myeloperoxidase

Cited by 89 publications

References 42 publications

Human Indoleamine 2,3-Dioxygenase Is a Catalyst of Physiological Heme Peroxidase Reactions

Human Indoleamine 2,3-Dioxygenase Is a Catalyst of Physiological Heme Peroxidase Reactions

Correlation between Gliotoxin Production and Virulence of Aspergillus fumigatus in Galleria mellonella

Superoxide-dependent Oxidation of Melatonin by Myeloperoxidase

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