Abstract
Isoniazid (INH), a front-line antituberculosis agent, is activated by mycobacterial catalase-peroxidase KatG, converting INH into bactericidal reactive species. Here we investigated the requirements and the pathway of nitric oxide (NO*) generation during oxidative activation of INH by Mycobacterium tuberculosis KatG in vitro. We also provide in vivo evidence that INH-derived NO* can inhibit key mycobacterial respiratory enzymes, which may contribute to the overall antimycobacterial action of INH.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aconitate Hydratase / metabolism
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Antitubercular Agents / metabolism
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Antitubercular Agents / pharmacology
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Bacterial Proteins*
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Catalase*
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Drug Resistance, Bacterial
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Electron Transport Complex IV / metabolism
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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Hydrogen Peroxide / metabolism
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Isocitrate Dehydrogenase / metabolism
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Isoniazid / metabolism*
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Isoniazid / pharmacology*
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Mycobacterium tuberculosis / drug effects*
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Mycobacterium tuberculosis / metabolism*
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Nitric Oxide / metabolism*
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Oxidation-Reduction
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Oxidoreductases / metabolism
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Spin Trapping
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Superoxides / metabolism
Substances
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Antitubercular Agents
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Bacterial Proteins
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Enzyme Inhibitors
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Superoxides
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Nitric Oxide
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Hydrogen Peroxide
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Oxidoreductases
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Isocitrate Dehydrogenase
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Catalase
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katG protein, Mycobacterium tuberculosis
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Electron Transport Complex IV
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Aconitate Hydratase
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Isoniazid