The Fenton oxidation mechanism: reactivities of biologically relevant substrates with two oxidizing intermediates differ from those predicted for the hydroxyl radical.

Wink, David A.; Nims, Raymond W.; Saavedra, Joseph E.; Utermahlen, W E; Ford, Peter C.

doi:10.1073/pnas.91.14.6604

Cited by 135 publications

(74 citation statements)

References 19 publications

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“…7). These ions most likely react with peroxide to form a metal-oxo complex or ⅐ OH through Fenton-type chemistry (57,58 Although there were differences in the relative efficacy of each ion to catalyze nitration, this could be attributed to differences in solubility or additionally to possible variations in preference for different protein ligand environments. In direct contrast to hemin, nitration by Fe 2ϩ during the NO͞O 2 Ϫ reaction resulted in nitration only at limited fluxes ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Protein nitration is mediated by heme and free metals through Fenton-type chemistry: An alternative to the NO/O\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation}{\mathrm{_{2}^{-}}}\end{equation}\end{document} reaction

Thomas

Espey

Vitek

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

176

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The chemical origins of nitrated tyrosine residues (NT) formed in proteins during a variety of pathophysiological conditions remain controversial. Although numerous studies have concluded that NT is a signature for peroxynitrite (ONOO ؊ ) formation, other works suggest the primary involvement of peroxidases. Because metal homeostasis is often disrupted in conditions bearing NT, the role of metals as catalysts for protein nitration was examined. nitrotyrosine ͉ nitric oxide ͉ peroxynitrite ͉ oxidation ͉ hemin N itrated tyrosine residues (NT) have been used as a marker of the involvement of nitric oxide (NO) and its related chemistry in a number of pathophysiological disorders including cardiovascular (1, 2) neurodegenerative and malignant conditions (1-5), such as septic shock (6), multiple sclerosis (7), Alzheimer's disease (8), and amyotrophic lateral sclerosis (9). In cancer the presence of NT often correlates with a poor prognosis (10), suggesting diagnostic implications.Several mechanisms for NT formation have been proposed, and its origin remains controversial (11-16). Detection of NT in vitro following exposure to synthetic peroxynitrite (ONOO Ϫ ) initially suggested that the reaction of NO with superoxide (O 2 Ϫ ) may be the primary source of NT (17,18). Further studies demonstrated that cogeneration of NO and O 2 Ϫ gave dissimilar results than bolus synthetic ONOO Ϫ (12,19,20). These disparities in nitration yields arose from further reactions of ONOO Ϫ with excess NO or O 2 Ϫ (21). Given the complexity of this seemingly simple reaction, much debate has ensued over the likelihood of NT formation under biologically relevant conditions (12,14).In addition to a ONOO Ϫ -mediated pathway, NT formation has been shown to result from the catalysis of nitrite oxidation by peroxidases, thus providing an alternate mechanism for its formation in vivo (22-24). Although leukocyte peroxidases likely account for a substantial amount of NT production in vivo, this mechanism fails to explain NT formation in the absence of inflammatory cells or peroxidases [i.e., a MPO Ϫ/Ϫ mouse model (25)].NT has been shown to occur on distinct proteins rather than in an indiscriminate manner (26). This may result from variations in protein susceptibility to nitration due to conformational differences or to association with redox active metals (27,28). We evaluated the relative efficacy of the synthetic ONOO Ϫ , NO͞O 2 Ϫ cogeneration, peroxidase, and redox active metal pathways to promote NT formation. Materials and MethodsBSA (essentially globulin-free), ribonuclease A, ferriprotoporphyrin IX (hemin), superoxide dismutase (SOD; bovine erythrocytes), cytochrome c, horseradish peroxidase (HRP), catalase (Cat), hypoxanthine (HX), myoglobin (horse heart), 2,2Ј-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), FeSO 4 , diethylenetriaminepentaacetic acid (DTPA), dimethylformamide (DMF), ␤-amyloid (1-42) protein (A␤), MnO 2 , and CuCl 2 were purchased from Sigma-Aldrich. H 2 O 2 , NaHCO 3 , NaNO 2 , and FeCl 3 were from Fisher Scientific....

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Section: Discussionmentioning

confidence: 99%

Protein nitration is mediated by heme and free metals through Fenton-type chemistry: An alternative to the NO/O\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation}{\mathrm{_{2}^{-}}}\end{equation}\end{document} reaction

Thomas

Espey

Vitek

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

176

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“…The absolute increase in the level of ortho-tyrosine was ϳ10-fold higher than that of o,oЈ-dityrosine. It should be noted that copper plus H 2 O 2 is a metal-catalyzed oxidation system that generates other reactive species in addition to HO ⅐ (42,43). In vitro studies have demonstrated, however, that the relative product yields of o,oЈ-dityrosine and ortho-tyrosine are similar in model proteins exposed to copper plus H 2 O 2 or ionizing radiation (a relatively pure source of HO ⅐ ; Ref.…”

Section: -Nitrotyrosine Ooј-dityrosine and Ortho-tyrosine In Braimentioning

confidence: 99%

Mass Spectrometric Quantification of 3-Nitrotyrosine, ortho-Tyrosine, and o,o′-Dityrosine in Brain Tissue of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated Mice, a Model of Oxidative Stress in Parkinson's Disease

Pennathur¹,

Jackson‐Lewis²,

Przedborski³

et al. 1999

Journal of Biological Chemistry

260

180

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Oxidative stress is implicated in the death of dopaminergic neurons in Parkinson's disease and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Oxidative species that might mediate this damage include hydroxyl radical, tyrosyl radical, or reactive nitrogen species such as peroxynitrite. In mice, we showed that MPTP markedly increased levels of o,o-dityrosine and 3-nitrotyrosine in the striatum and midbrain but not in brain regions resistant to MPTP. These two stable compounds indicate that tyrosyl radical and reactive nitrogen species have attacked tyrosine residues. In contrast, MPTP failed to alter levels of ortho-tyrosine in any brain region we studied. This marker accumulates when hydroxyl radical oxidizes protein-bound phenylalanine residues. We also showed that treating whole-brain proteins with hydroxyl radical markedly increased levels of ortho-tyrosine in vitro. Under identical conditions, tyrosyl radical, produced by the heme protein myeloperoxidase, selectively increased levels of o,o-dityrosine, whereas peroxynitrite increased levels of 3-nitrotyrosine and, to a lesser extent, of ortho-tyrosine. These in vivo and in vitro findings implicate reactive nitrogen species and tyrosyl radical in MPTP neurotoxicity but argue against a deleterious role for hydroxyl radical in this model. They also show that reactive nitrogen species and tyrosyl radical (and consequently protein oxidation) represent an early and previously unidentified biochemical event in MPTP-induced brain injury. This finding may be significant for understanding the pathogenesis of Parkinson's disease and developing neuroprotective therapies.

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“…The main experimental evidence is based on the capacity of Fenton reaction to oxidate substrates in the presence of •OH quenchers (24)(25)(26) . Ferryl intermediary in Fenton reaction was proposed by Brain y Gorin (27) , according to (8 (28) , UV/Vis stopped-flow kinetic (29), pulse radiolysis on peroxo-complexes in aqueous solution (30) and chemiluminescence data (31,32) .…”

Section: Fe(iv) and Singlet Oxygen In Fenton Reactionmentioning

confidence: 99%

Fenton Reaction Driven by Iron Ligands

Salgado

Melín

Contreras

et al. 2013

J. Chil. Chem. Soc.

107

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One of the most important sources of reactive oxygen species (ROS) in biological systems is the Fenton reaction. In this, the Fe 2+ or Fe 3+ reacts with H 2 O 2 to produce ROS as the hydroxyl radical (•OH), superoxide radical (O 2 •-) and singlet oxygen ( 1 O 2 ). The main ROS, responsible for the high oxidizing power of the Fenton reaction, is not clear. Some authors claim that the principal reactive species is •OH, while others propose a ferryl specie (Fe 4+ or [FeO] 2+ ) (1,2) . Recently, have been proposed that the kind of reaction species produced depends mainly of pH and the iron composition of the coordination sphere. This is highlighted for Fe 3+ , because in mono and (some) bis-complexes Fe 3+ is reduced to Fe 2+ and there are some positions occupied by water or hydroxide ligands, readily to be exchanged by H 2 O 2 . On the other hand, in tris-complexes there are not any positions occupied by water or hydroxide, avoiding the formation of peroxo-complexes, necessary for Fenton or Fenton like reaction.The 1,2-dihydroxybenzenes (DHBs) have been described as modulators of Fenton reaction. The DHBs driven Fenton reaction have been used for environmental applications as an advanced oxidation process. Furthermore, these systems participate in different biological process, as the wood biodegradation by fungi and oxidative stress in neurodegenerative diseases.In this review, the effect of 1,2-dihydroxybenzenes on the activated species production by the Fenton and Fenton like reaction will be discussed and its participation in different systems.

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The Fenton oxidation mechanism: reactivities of biologically relevant substrates with two oxidizing intermediates differ from those predicted for the hydroxyl radical.

Cited by 135 publications

References 19 publications

Mass Spectrometric Quantification of 3-Nitrotyrosine, ortho-Tyrosine, and o,o′-Dityrosine in Brain Tissue of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated Mice, a Model of Oxidative Stress in Parkinson's Disease

Fenton Reaction Driven by Iron Ligands

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