Aromatic hydroxylation during the myeloperoxidase-oxidase oxidation of hydrazines

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dc.contributor.authorVan Der Walt B.J.
dc.contributor.authorVan Zyl J.M.
dc.contributor.authorKriegler A.
dc.date.accessioned2011-05-15T16:01:17Z
dc.date.available2011-05-15T16:01:17Z
dc.date.issued1994
dc.description.abstractBenzoic acid was found to be hydroxylated by a mixture of myeloperoxidase (MPO) and the mycobactericidal drug, isoniazid. Aromatic hydroxylation and formation of compound III (oxyperoxidase) were coincident during the MPO-oxidase oxidation of isoniazid which proceeded without augmentation from the reagent hydrogen peroxide. An intermediate of isoniazid reduced ferric MPO to ferrous MPO which associated with dioxygen to form compound III. Aromatic hydroxylation also occurred in a mixture of isoniazid (or phenylhydrazine) and a ferric salt. Hydroxylations in both the enzymatic and nonenzymatic reaction systems were inhibited by the iron chelator, desferal, as well as by the specific hydroxyl radical scavenger, mannitol. To distinguish between the hydroxylating intermediates in the different reaction systems, the unique properties of the natural antioxidant, phytic acid, were exploited. Phytic acid inhibited aromatic hydroxylation in the Fe3+-INH system, which is in accordance with its known properties as a powerful inhibitor of iron-driven reactions (·OH formation). By contrast, phytic acid stimulated hydroxylation in the enzymatic system which was accompanied by a concomitant stimulation in the rate of compound III formation. These events were, however, not directly related to each other. Phytic acid had a direct effect on the redox transformation of isoniazid by stimulating superoxide generation during auto-oxidation of the drug. In addition, phytic acid also facilitated compound III decay in the absence of isoniazid, suggesting that it may also regulate the oxygen affinity of MPO, similar to its effect on the oxygenation of haemoglobin. The data on aromatic hydroxylation in the MPO-isoniazid system do not support a role for ·OH in the reaction and may fit the model for the P450 mixed oxidase system.
dc.description.versionArticle
dc.identifier.citationBiochemical Pharmacology
dc.identifier.citation47
dc.identifier.citation6
dc.identifier.issn62952
dc.identifier.other10.1016/0006-2952(94)90415-4
dc.identifier.urihttp://hdl.handle.net/10019.1/11904
dc.subjectbenzoic acid
dc.subjectcatalase
dc.subjecthydrazine derivative
dc.subjectisoniazid
dc.subjectmyeloperoxidase
dc.subjectphytic acid
dc.subjectsuperoxide dismutase
dc.subjectarticle
dc.subjecthydroxylation
dc.subjectpriority journal
dc.subjectCatalysis
dc.subjectHuman
dc.subjectHydrazines
dc.subjectHydrogen Peroxide
dc.subjectHydroxylation
dc.subjectIron
dc.subjectOxidation-Reduction
dc.subjectOxidoreductases
dc.subjectPeroxidase
dc.titleAromatic hydroxylation during the myeloperoxidase-oxidase oxidation of hydrazines
dc.typeArticle
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