On the mechanism of nitric oxide formation upon oxidative cleavage of CN(OH) bonds by NO-synthases and cytochromes P450

Evaluation of Nitric Oxide-Donating Properties of 11H-indeno[1,2-b]quinoxalin-11-one Oxime (IQ-1) by Electron Paramagnetic Resonance Spectroscopy

“…According to the literature data, ketoximes and amidoximes can be oxidized by CYP450 with the release of NO via the intermediate formation of O 2 · − , the latter being a dissociation product of the CYP450–Fe 2+ –O 2 complex [ 31 ]. The proposed mechanism of the C=N−OH group oxidative transformation “outside the active site” [ 33 ] involves the nucleophilic attack of O 2 · − to the oxime carbon atom and the further transfer of the electron pairs within the anion–radical adduct A · − ( Scheme 2 ).…”

Evaluation of Nitric Oxide-Donating Properties of 11H-indeno[1,2-b]quinoxalin-11-one Oxime (IQ-1) by Electron Paramagnetic Resonance Spectroscopy

“…According to the literature data, ketoximes and amidoximes can be oxidized by CYP450 with the release of NO via the intermediate formation of O 2 · − , the latter being a dissociation product of the CYP450–Fe 2+ –O 2 complex [ 31 ]. The proposed mechanism of the C=N−OH group oxidative transformation “outside the active site” [ 33 ] involves the nucleophilic attack of O 2 · − to the oxime carbon atom and the further transfer of the electron pairs within the anion–radical adduct A · − ( Scheme 2 ).…”

Phenyl 2‐pyridyl ketoxime induces cellular senescence‐like alterations via nitric oxide production in human diploid fibroblasts

“…Ketoximes have been shown to produce NO in vivo via NADPH‐dependent microsomal metabolism by P450 in hepatic tissues (Mansuy et al ., 1995; Jousserandot et al ., 1998; Caro et al ., 2001). Furthermore, acetoxime was not found to be active as a substrate or as an inhibitor of iNOS in E47 HepG2 hepatic cell line, which expresses CYP2E1, and thus, it was suggested that acetoxime‐dependent NO generation can be catalyzed by cytochrome P450 but not by NOS in hepatic cell lines (Caro et al ., 2001).…”

Reactions Catalyzed by the Heme Domain of Inducible Nitric Oxide Synthase: Evidence for the Involvement of Tetrahydrobiopterin in Electron Transfer

“…The mixture of urea and cyanamide amino acid products is similar to what is observed for oxidation reactions of N -hydroxyguanidines catalyzed by cytochrome P450 ( − ). In these reactions, where the substrate may not be well positioned to react with Fe III O 2 • directly, oxidation is proposed to occur by reaction with superoxide dissociated from the P450 heme ( , ). The possible involvement of superoxide in the reaction of pterin-free iNOS heme was not investigated here, although there are conflicting reports in the literature concerning whether superoxide is involved in the oxidation of NHA catalyzed by pterin-free NOS ( , ).…”

Evaluation of Nitric Oxide-Donating Properties of 11H-indeno[1,2-b]quinoxalin-11-one Oxime (IQ-1) by Electron Paramagnetic Resonance Spectroscopy

“…According to the literature data, ketoximes and amidoximes can be oxidized by CYP450 with the release of NO via the intermediate formation of O 2 · − , the latter being a dissociation product of the CYP450–Fe 2+ –O 2 complex [ 31 ]. The proposed mechanism of the C=N−OH group oxidative transformation “outside the active site” [ 33 ] involves the nucleophilic attack of O 2 · − to the oxime carbon atom and the further transfer of the electron pairs within the anion–radical adduct A · − ( Scheme 2 ).…”

Phenyl 2‐pyridyl ketoxime induces cellular senescence‐like alterations via nitric oxide production in human diploid fibroblasts

“…Ketoximes have been shown to produce NO in vivo via NADPH‐dependent microsomal metabolism by P450 in hepatic tissues (Mansuy et al ., 1995; Jousserandot et al ., 1998; Caro et al ., 2001). Furthermore, acetoxime was not found to be active as a substrate or as an inhibitor of iNOS in E47 HepG2 hepatic cell line, which expresses CYP2E1, and thus, it was suggested that acetoxime‐dependent NO generation can be catalyzed by cytochrome P450 but not by NOS in hepatic cell lines (Caro et al ., 2001).…”

Reactions Catalyzed by the Heme Domain of Inducible Nitric Oxide Synthase: Evidence for the Involvement of Tetrahydrobiopterin in Electron Transfer

“…The mixture of urea and cyanamide amino acid products is similar to what is observed for oxidation reactions of N -hydroxyguanidines catalyzed by cytochrome P450 ( − ). In these reactions, where the substrate may not be well positioned to react with Fe III O 2 • directly, oxidation is proposed to occur by reaction with superoxide dissociated from the P450 heme ( , ). The possible involvement of superoxide in the reaction of pterin-free iNOS heme was not investigated here, although there are conflicting reports in the literature concerning whether superoxide is involved in the oxidation of NHA catalyzed by pterin-free NOS ( , ).…”

Evaluation of Nitric Oxide-Donating Properties of 11H-indeno[1,2-b]quinoxalin-11-one Oxime (IQ-1) by Electron Paramagnetic Resonance Spectroscopy

“…According to the literature data, ketoximes and amidoximes can be oxidized by CYP450 with the release of NO via the intermediate formation of O 2 · − , the latter being a dissociation product of the CYP450–Fe 2+ –O 2 complex [ 31 ]. The proposed mechanism of the C=N−OH group oxidative transformation “outside the active site” [ 33 ] involves the nucleophilic attack of O 2 · − to the oxime carbon atom and the further transfer of the electron pairs within the anion–radical adduct A · − ( Scheme 2 ).…”

Phenyl 2‐pyridyl ketoxime induces cellular senescence‐like alterations via nitric oxide production in human diploid fibroblasts

“…Ketoximes have been shown to produce NO in vivo via NADPH‐dependent microsomal metabolism by P450 in hepatic tissues (Mansuy et al ., 1995; Jousserandot et al ., 1998; Caro et al ., 2001). Furthermore, acetoxime was not found to be active as a substrate or as an inhibitor of iNOS in E47 HepG2 hepatic cell line, which expresses CYP2E1, and thus, it was suggested that acetoxime‐dependent NO generation can be catalyzed by cytochrome P450 but not by NOS in hepatic cell lines (Caro et al ., 2001).…”

Reactions Catalyzed by the Heme Domain of Inducible Nitric Oxide Synthase: Evidence for the Involvement of Tetrahydrobiopterin in Electron Transfer

“…The mixture of urea and cyanamide amino acid products is similar to what is observed for oxidation reactions of N -hydroxyguanidines catalyzed by cytochrome P450 ( − ). In these reactions, where the substrate may not be well positioned to react with Fe III O 2 • directly, oxidation is proposed to occur by reaction with superoxide dissociated from the P450 heme ( , ). The possible involvement of superoxide in the reaction of pterin-free iNOS heme was not investigated here, although there are conflicting reports in the literature concerning whether superoxide is involved in the oxidation of NHA catalyzed by pterin-free NOS ( , ).…”