ChemInform Abstract: Reactions of Monochloramine with Br2, Br‐ 3, HOBr, and OBr‐: Formation of Bromochloramines.

Gazda, Michael; Margerum, Dale W.

doi:10.1002/chin.199419013

Cited by 12 publications

(27 citation statements)

References 1 publication

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“…Hypochlorite was freshly prepared before each experiment by the dilution of a 10-15% stock solution of NaOCl into a solution of 0.9% NaCl and its concentration was determined spectrophotometrically by the absorbance peak of – OCl at 292 nm (ε = 350 M −1 cm −1 ) at a pH range of 10-12 (17). The concentration of HOCl in the resistance assay ranged from 0-100 μM.…”

Section: Methodsmentioning

confidence: 99%

Selenocysteine Confers Resistance to Inactivation by Oxidation in Thioredoxin Reductase: Comparison of Selenium and Sulfur Enzymes

Snider

Ruggles

Khan³

et al. 2013

Biochemistry

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Mammalian thioredoxin reductase (TR) is a selenocysteine (Sec)-containing homodimeric pyridine nucleotide oxidoreductase which catalyzes the reduction of oxidized thioredoxin. We have previously demonstrated the full-length mitochondrial mammalian TR (mTR3) enzyme to be resistant to inactivation from exposure to 50 mM H2O2. Because a Sec residue oxidizes more rapidly than a cysteine (Cys) residue, it has been previously thought that Sec-containing enzymes are “sensitive to oxidation” compared to Cys-orthologs. Here we show for the first time a direct comparison of the abilities of Sec-containing mTR3 and the Cys-ortholog from D. melanogaster (DmTR) to resist inactivation by oxidation from a variety of oxidants including H2O2, hydroxyl radical, peroxynitrite, hypochlorous acid, hypobromous acid, and hypothiocyanous acid. The results show that the Sec-containing TR is far superior to the Cys-ortholog TR in resisting inactivation by oxidation. To further test our hypothesis that the use of Sec confers strong resistance to inactivation by oxidation, we constructed a chimeric enzyme in which we replaced the active site Cys nucleophile of DmTR with a Sec residue using semisynthesis. The chimeric Sec-containing enzyme has similar ability to resist inactivation by oxidation as the wild type Sec-containing TR from mouse mitochondria. The use of Sec in the chimeric enzyme “rescued” the enzyme from oxidant-induced inactivation for all of the oxidants tested in this study, in direct contrast to previous understanding. We discuss two possibilities for this rescue effect from inactivation under identical conditions of oxidative stress: (i) Sec resists over-oxidation and inactivation, whereas a Cys residue can be permanently over-oxidized to the sulfinic acid form, and (ii) Sec protects the body of the enzyme from harmful oxidation by allowing the enzyme to metabolize (turnover) various oxidants much better than a Cys-containing TR.

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Section: Methodsmentioning

confidence: 99%

Selenocysteine Confers Resistance to Inactivation by Oxidation in Thioredoxin Reductase: Comparison of Selenium and Sulfur Enzymes

Snider

Ruggles

Khan³

et al. 2013

Biochemistry

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“…Hydrogen peroxide solutions were prepared by diluting a 30 % stock solution (Merck) and calculating its concentration using a ε 240 of 43.6 M −1 • cm −1 [18]. Hypochlorous acid solutions were prepared by diluting a concentrated commercial bleach solution and calculating its concentration using a ε 292 of 350 M −1 • cm −1 at pH 12 [19]. Stock solutions of serotonin were prepared daily in water.…”

Section: Introductionmentioning

confidence: 99%

Serotonin as a physiological substrate for myeloperoxidase and its superoxide-dependent oxidation to cytotoxic tryptamine-4,5-dione

Ximenes

Maghzal

Turner

et al. 2009

Biochemical Journal

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During inflammatory events, neutrophils and platelets interact to release a variety of mediators. Neutrophils generate superoxide and hydrogen peroxide, and also discharge the haem enzyme myeloperoxidase. Among numerous other mediators, platelets liberate serotonin (5-hydroxytryptamine), which is a classical neurotransmitter and vasoactive amine that has significant effects on inflammation and immunity. In the present study, we show that serotonin is a favoured substrate for myeloperoxidase because other physiological substrates for this enzyme, including chloride, did not affect its rate of oxidation. At low micromolar concentrations, serotonin enhanced hypochlorous acid production by both purified myeloperoxidase and neutrophils. At higher concentrations, it almost completely blocked the formation of hypochlorous acid. Serotonin was oxidized to a dimer by myeloperoxidase and hydrogen peroxide. It was also converted into tryptamine-4,5-dione, especially in the presence of superoxide. This toxic quinone was produced by stimulated neutrophils in a reaction that required myeloperoxidase. In plasma, stimulated human neutrophils oxidized serotonin to its dimer using the NADPH oxidase and myeloperoxidase. We propose that myeloperoxidase will oxidize serotonin at sites of inflammation. In doing so, it will impair its physiological functions and generate a toxic metabolite that will exacerbate inflammatory tissue damage. Consequently, oxidation of serotonin by myeloperoxidase may profoundly influence inflammatory processes.

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“…All bromamine studies were performed in 0.1 M phosphate buffer (pH 7.4), with the latter prepared using MilliQ water treated with Chelex resin (Bio-Rad) to remove contaminating metal ions. HOBr was prepared by mixing equal volumes of 20 mM HOCl and 22 mM NaBr [27].…”

Section: Methodsmentioning

confidence: 99%

Hypobromous acid and bromamine production by neutrophils and modulation by superoxide

Chapman

Skaff

Senthilmohan

et al. 2009

Biochemical Journal

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MPO (myeloperoxidase) catalyses the oxidation of chloride, bromide and thiocyanate to their respective hypohalous acids. We have investigated the generation of HOBr by human neutrophils in the presence of physiological concentrations of chloride and bromide. HOBr was trapped with taurine and detected by monitoring the bromination of 4-HPAA (4-hydroxyphenylacetic acid). With 100 microM bromide and 140 mM chloride, neutrophils generated HOBr and it accounted for approx. 13% of the hypohalous acids they produced. Addition of SOD (superoxide dismutase) doubled the amount of HOBr detected. Therefore we investigated the reaction of superoxide radicals with a range of bromamines and bromamides and found that superoxide radicals stimulated the decomposition of these species, with this occurring in a time- and dose-dependent manner. The protection afforded by SOD against such decay demonstrates that these processes are superoxide-radical-dependent. These data are consistent with neutrophils generating HOBr at sites of infection and inflammation. Both HOBr and bromamines/bromamides have the potential to react with superoxide radicals to form additional radicals that may contribute to inflammatory tissue damage.

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ChemInform Abstract: Reactions of Monochloramine with Br2, Br‐ 3, HOBr, and OBr‐: Formation of Bromochloramines.

Cited by 12 publications

References 1 publication

Selenocysteine Confers Resistance to Inactivation by Oxidation in Thioredoxin Reductase: Comparison of Selenium and Sulfur Enzymes

Selenocysteine Confers Resistance to Inactivation by Oxidation in Thioredoxin Reductase: Comparison of Selenium and Sulfur Enzymes

Serotonin as a physiological substrate for myeloperoxidase and its superoxide-dependent oxidation to cytotoxic tryptamine-4,5-dione

Hypobromous acid and bromamine production by neutrophils and modulation by superoxide

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