Activation of Triplet Dioxygen by Glucose Oxidase:  Spin−Orbit Coupling in the Superoxide Ion

Prabhakar, Rajeev; Siegbahn, Per E. M.; Minaev, B. F.; Ågren, Hans

doi:10.1021/jp014013q

Cited by 79 publications

(149 citation statements)

References 36 publications

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“…In addition, one of the steps preceding the second reduction may be slow [intersystem crossing (40) (31). In complex I, the flavin radical is thermodynamically unstable (30), supporting redistribution, but it is not possible to identify a single FeS cluster to oxidize (or re-reduce) it.…”

Section: Discussionmentioning

confidence: 99%

The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria

Kußmaul

Hirst

2006

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

642

561

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NADH:ubiquinone oxidoreductase (complex I) is a major source of reactive oxygen species in mitochondria and a significant contributor to cellular oxidative stress. Here, we describe the kinetic and molecular mechanism of superoxide production by complex I isolated from bovine heart mitochondria and confirm that it produces predominantly superoxide, not hydrogen peroxide. Redox titrations and electron paramagnetic resonance spectroscopy exclude the iron-sulfur clusters and flavin radical as the source of superoxide, and, in the absence of a proton motive force, superoxide formation is not enhanced during turnover. Therefore, superoxide is formed by the transfer of one electron from fully reduced flavin to O2. The resulting flavin radical is unstable, so the remaining electron is probably redistributed to the iron-sulfur centers. The rate of superoxide production is determined by a bimolecular reaction between O2 and reduced flavin in an empty active site. The proportion of the flavin that is thus competent for reaction is set by a preequilibrium, determined by the dissociation constants of NADH and NAD ؉ , and the reduction potentials of the flavin and NAD ؉ . Consequently, the ratio and concentrations of NADH and NAD ؉ determine the rate of superoxide formation. This result clearly links our mechanism for the isolated enzyme to studies on intact mitochondria, in which superoxide production is enhanced when the NAD ؉ pool is reduced. Therefore, our mechanism forms a foundation for formulating causative connections between complex I defects and pathological effects.flavin ͉ iron-sulfur cluster ͉ semiquinone ͉ oxidative stress T he production of reactive oxygen species, such as superoxide, by mitochondria is a major cause of cellular oxidative stress. It contributes to many pathological conditions such as Parkinson's and other neurodegenerative diseases, ischemia reperfusion injury, atherosclerosis, and aging (1-3). In mammalian mitochondria, most of the superoxide originates from NADH:ubiquinone oxidoreductase (complex I) and ubiquinol: cytochrome c oxidoreductase (complex III) of the electron transport chain, but there is increasing evidence that superoxide production by complex I, into the mitochondrial matrix, is predominant (4, 5). Indeed, complex I deficiencies have been identified across a wide spectrum of pathologies and linked to enhanced superoxide production as well as to deficiencies in energy production (6-10). Therefore, it is imperative to define how, why, and when superoxide is produced by complex I to formulate causative connections with pathological effects and rational proposals for how defects may be addressed.Many previous studies have addressed the question of how superoxide is produced by complex I (11-18). Most of these studies examined intact mitochondria or submitochondrial particles, in which it is difficult to correlate observations directly to complex I, or to define and control the conditions precisely (NADH, NAD ϩ , ubiquinone, and ubiquinol concentrations, redox status, proton motive...

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Section: Discussionmentioning

confidence: 99%

The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria

Kußmaul

Hirst

2006

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

642

561

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“…Molecular oxygen in the ground state is a diradical species presenting two unpaired electrons in the same spin and therefore has a triplet spin state (spectroscopic term: 3  g -). 50 This has implications of central importance for oxidation reactions of organic substrates, either those involving oxygen insertion into a hydrocarbon skeleton or oxidative dehydrogenation by oxygen species. In fact, organic substrates (hydrocarbons, alcohols, ketons and acids) in the ground state all have a closed shell electronic structures, and therefore are in a singlet state.…”

Section: Reactivity Of Oxygenmentioning

confidence: 99%

Catalytic oxygen activation versus autoxidation for industrial applications: a physicochemical approach

Liu

Ryabenkova

Conte

2015

Phys. Chem. Chem. Phys.

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The activation and use of oxygen for the oxidation and functionalization of organic substrates is among the most important reactions in a chemist's toolbox. Nevertheless, despite the vast literature on catalytic oxidation, the phenomenon of autoxidation, an ever-present background reaction that occurs in virtually every oxidation process, is often neglected. In contrast, autoxidation can affect the selectivity to a desired product, to those dictated by pure freeradical chain pathways, thus affecting the activity of any catalyst used to carry out a reaction.This critical review compares catalytic oxidation routes by transition metals versus autoxidation, particularly focusing on the industrial context, where highly selective and "green" processes are needed. Furthermore, the application of useful tests to discriminate between different oxygen activation routes, especially in the area of hydrocarbon oxidation, with the aim of an enhanced catalyst design, is described and discussed. In fact, one of the major targets of selective oxidation is the use of molecular oxygen as ultimate oxidant, combined with the development of catalysts capable to perform the catalytic cycle in a real energy and cost effective manner on a large scale. To achieve this goal, insights from metallo-proteins that could find application in some areas of industrial catalysis are presented, as well as considering the physicochemical principles that are at the fundament of oxidation and autoxidation processes.3

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“…Despite its openshell nature, dioxygen exhibits relatively low reactivity. This feature is related to the triplet-singlet spin barrier [2], which can be circumvented upon O 2 activation on catalytic surfaces via complex networks of redox processes until the terminal O 2-ion is formed [1,3]. It involves a sequence of gradual reduction and dissociation steps including O 2(g) ?…”

Section: Introductionmentioning

confidence: 99%

“…Unlike diamagnetic O 2 2-and O 2-anions, the O -and O 2 -oxygen species are paramagnetic and may be observed directly by means of EPR spectroscopy [9][10][11]. These radicals, especially when isotopically enriched 17 O 2 is used, exhibit characteristic spectra of high information content, which allows one to characterize their molecular structure, formation, thermal stability, and reactivity.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Features of EPR Spectra of Superoxide Intermediates on Catalytic Surfaces and Molecular Interpretation of Their g and A Tensors

et al. 2015

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The use of electron paramagnetic resonance spectroscopy to study the superoxide intermediates, generated by end-on and side-on adsorption of the naturally abundant and 17 O-enriched dioxygen on catalytic surfaces is discussed. Basic mechanisms of O 2 -radical formation via a cationic redox mechanism, an anionic redox mechanism, and an electroprotic mechanism are illustrated with selected oxide-based systems of catalytic relevance. Representative experimental spectra of various complexities are analyzed and their diagnostic features have been identified and interpreted. The molecular nature of the g and A tensors of the electrostatic and covalent superoxide adducts is discussed in detail within the classic and density functional theory based approaches.

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Activation of Triplet Dioxygen by Glucose Oxidase: Spin−Orbit Coupling in the Superoxide Ion

Cited by 79 publications

References 36 publications

The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria

The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria

Catalytic oxygen activation versus autoxidation for industrial applications: a physicochemical approach

Diagnostic Features of EPR Spectra of Superoxide Intermediates on Catalytic Surfaces and Molecular Interpretation of Their g and A Tensors

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