Reactions of nitric oxide with cytochrome c oxidase

Brudvig, Gary W.; Stevens, Tom H.; Chan, Sunney I.

doi:10.1021/bi00564a020

Cited by 243 publications

(179 citation statements)

References 20 publications

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“…1,Cl that i and o redox centres may be situated on either side of CUB is consistent with the conclusion, drawn from optical absorption, EPR and MCD studies, that ligands, such as NO and CN- [18], or NO and NT [19,20], or CO and Hz0 [21] may be simultaneously bound at separate centres neighbouring CUB, and that electrons may be conducted between these centres, presumably via CUB ( [21,22] and see [23,24]). It is also consistent with the inference that, on photolysis of the CO compound of the oxidase, the CO migrates from a site between a3 and CUB to a pocket neighbouring CUB [25-271. It is a fundamental, and potentially diagnostic, attribute of the protonmotive 0 loop flow system ( fig.…”

Section: Protonmotive 0 Loop Mechanismssupporting

confidence: 84%

Chemiosmotic coupling in cytochrome oxidase

Mitchell

Moody

et al. 1985

FEBS Letters

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Using the principle of specific vectorial ligand conduction, we outline directly coupled protonmotive O loop and O cycle mechanisms of cytochrome oxidase action that are analogous to protonmotive Q loop and Q cycle mechanisms of QH2 dehydrogenase action. We discuss these directly coupled mechanisms in the light of available experimental knowledge, and suggest that they may stimulate useful new research initiatives designed to elucidate the osmochemistry of protonmotive oxygen reduction in cytochrome oxidase.

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Section: Protonmotive 0 Loop Mechanismssupporting

confidence: 84%

Chemiosmotic coupling in cytochrome oxidase

Mitchell

Moody

et al. 1985

FEBS Letters

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“…Although the precise mechanism of the NO 2 Ϫ reduction in Cco remains to be determined, it is useful to note that a NO 2 Ϫ -ferric a 3 complex has been observed in studies aimed at examining the interaction between NO and Cco (53)(54)(55)(56). Moreover, it has been reported that a heme-nitrosyl complex is formed at the binuclear reaction center in bovine heart Cco when incubated in the presence of excess NO 2 Ϫ and reductant (57). These findings suggest that the one-electron reduction of NO 2 Ϫ to NO occurs at the binuclear reaction center and raise the possibility that under anoxic/hypoxic conditions a step in the catalytic cycle [e.g., (58) that is involved in the generation of NO 2 Ϫ from NO is merely reversed during the reduction of NO 2 Ϫ to NO, and that the reversal of this reaction is favored at low oxygen levels or the low pHs experienced by anoxic cells (59,60).…”

Section: Discussionmentioning

confidence: 99%

Oxygen-regulated isoforms of cytochrome c oxidase have differential effects on its nitric oxide production and on hypoxic signaling

Castello

Woo

Ball

et al. 2008

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

103

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Recently, it has been reported that mitochondria possess a novel pathway for nitric oxide (NO) synthesis. This pathway is induced when cells experience hypoxia, is nitrite (NO 2 ؊ )-dependent, is independent of NO synthases, and is catalyzed by cytochrome c oxidase (Cco). It has been proposed that this mitochondrially produced NO is a component of hypoxic signaling and the induction of nuclear hypoxic genes. In this study, we examine the NO 2 ؊ -dependent NO production in yeast engineered to contain alternative isoforms, Va or Vb, of Cco subunit V. Previous studies have shown that these isoforms have differential effects on oxygen reduction by Cco, and that their genes (COX5a and COX5b, respectively) are inversely regulated by oxygen. Here, we find that the Vb isozyme has a higher turnover rate for NO production than the Va isozyme and that the Vb isozyme produces NO at much higher oxygen concentrations than the Va isozyme. We have also found that the hypoxic genes CYC7 and OLE1 are induced to higher levels in a strain carrying the Vb isozyme than in a strain carrying the Va isozyme. Together, these results demonstrate that the subunit V isoforms have differential effects on NO 2 ؊ -dependent NO production by Cco and provide further support for a role of Cco in hypoxic signaling. These findings also suggest a positive feedback mechanism in which mitochondrially produced NO induces expression of COX5b, whose protein product then functions to enhance the ability of Cco to produce NO in hypoxic/anoxic cells.hypoxia ͉ mitochondria ͉ reactive oxygen species ͉ nitrite ͉ yeast I t has been known for quite some time that the mitochondrial respiratory chain is capable of generating reactive oxygen species (ROS) that account for much of the oxidative stress experienced by cells (1-3). The levels of these ROS increase when electron flow through the respiratory chain is inhibited by respiratory inhibitors (4-6) or altered by uncoupling electron transport from oxidative phosphorylation (7,8). Several studies have shown that exposure of cells and tissues to hypoxia increases ROS levels and oxidative stress (9-11). This increase in oxidative stress during exposure to hypoxia depends on a functional mitochondrial respiratory chain (10). It is currently unclear whether this increase is the result of increased generation or decreased destruction of ROS under hypoxic conditions. In yeast cells, the increase in ROS levels and oxidative stress is transient, as determined by shifting cells from normoxia to anoxia (10). During this shift, cells experience a continuum of decreasing oxygen concentrations and a transient increase in the levels of carbonylation of both mitochondrial and cytosolic protein, an increase in 8-OH-dG levels in mtDNA, and an increase in expression of the SOD1 gene. Many of the proteins that are carbonylated during a shift from normoxia to anoxia are the same proteins that are carbonylated when cells are exposed to menadione, a redox recycling agent that produces elevated intracellular levels of superoxide (12). ...

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“…In eukaryotes CcO (aa 3 type) reduces O 2 to H 2 O and is reversibly but strongly inhibited by NO (17)(18)(19)(20). Several other CcOs (ba 3 , caa 3 , cbb 3 ) are reported to exhibit limited (Ͻ1%) NOR activity, i.e., reduce NO to N 2 O (7,21).…”

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confidence: 99%

O ₂ reduction by a functional heme/nonheme bis-iron NOR model complex

Collman

Dey

Yang

et al. 2009

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

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O2 reactivity of a functional NOR model is investigated by using electrochemistry and spectroscopy. The electrochemical measurements using interdigitated electrodes show very high selectivity for 4e O2 reduction with minimal production of partially reduced oxygen species (PROS) under both fast and slow electron flux. Intermediates trapped at cryogenic temperatures and characterized by using resonance Raman spectroscopy under single-turnover conditions indicate that an initial bridging peroxide intermediate undergoes homolytic OOO bond cleavage generating a trans heme/nonheme bis-ferryl intermediate. This bis ferryl species can oxygenate 2 equivalents of a reactive substrate.C ytochrome c oxidase (CcO) and nitric oxide reductase (NOR) belong to the heme copper oxidase superfamily of enzymes (1, 2). CcO is the terminal enzyme in the respiratory chain of higher organisms, located in their mitochondrial membrane, that reduces O 2 to H 2 O as source of energy. The O 2 reduction process in CcO generates a pH gradient across the bilayer membrane, which provides the driving force for ATP synthesis. The bimetallic active site of CcO has a heme ligated to the protein by a proximal histidine ligand and a distal Cu B site coordinated by 3 histidine ligands ( Fig. 1) (3). In addition to the bimetallic site, there is a conserved tyrosine ligand covalently attached to one of the histidines coordinated to Cu B (4, 5). The NORs are the older member of the family and are found in bacteria using NO 3 Ϫ as source of energy instead of O 2 (2, 6, 7). Although there are no high-resolution crystal structures of NOR, biochemical studies and computer modeling indicate that these enzymes have a histidine-ligated heme, quite like the CcOs, and a distal Fe B , unlike Cu B in CcO, coordinated by 3 histidines ( Fig. 1) (8-10). NORs do not have the conserved tyrosine residue of CcO but have a few conserved key glutamate residues (11,12). Although the NOR enzymes are proposed to have specific proton channels, they are probably not involved in generating proton gradients (13-16).These 2 enzymes exhibit complementary reactivity toward 2 very significant diatomic molecules in nature; O 2 and NO. In eukaryotes CcO (aa 3 type) reduces O 2 to H 2 O and is reversibly but strongly inhibited by [17][18][19][20]. Several other CcOs (ba 3 , caa 3 , cbb 3 ) are reported to exhibit limited (Ͻ1%) NOR activity, i.e., reduce NO to N 2 O (7, 21). On the other hand, NORs that reduce NO to N 2 O are reversibly but strongly inhibited by O 2 , and some of them show modest (Ϸ10%) O 2 reduction activity (12). The parallels in their reactivities toward O 2 and NO and similarities in their secondary structures have led to a hypotheses regarding NOR's and CcO's similar evolutionary origins (6,22).Electrochemistry is a very powerful technique that can provide fundamental insights into reaction mechanisms of redox catalysts (23-27). Conventionally, a catalyst is deposited on a conducting electrode material (e.g., graphite); however, this approach does not allow site isola...

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Reactions of nitric oxide with cytochrome c oxidase

Cited by 243 publications

References 20 publications

Chemiosmotic coupling in cytochrome oxidase

Chemiosmotic coupling in cytochrome oxidase

Oxygen-regulated isoforms of cytochrome c oxidase have differential effects on its nitric oxide production and on hypoxic signaling

O ₂ reduction by a functional heme/nonheme bis-iron NOR model complex

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Reactions of nitric oxide with cytochrome c oxidase

Cited by 243 publications

References 20 publications

Chemiosmotic coupling in cytochrome oxidase

Chemiosmotic coupling in cytochrome oxidase

Oxygen-regulated isoforms of cytochrome c oxidase have differential effects on its nitric oxide production and on hypoxic signaling

O 2 reduction by a functional heme/nonheme bis-iron NOR model complex

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O ₂ reduction by a functional heme/nonheme bis-iron NOR model complex