Reduction of Nitrite to Nitric Oxide Catalyzed by Xanthine Oxidoreductase

Godber, Ben; Doel, Justin J.; Sapkota, Gopal P.; Blake, David R.; Stevens, Cliff R.; Eisenthal, Robert; Harrison, Roger

doi:10.1074/jbc.275.11.7757

Cited by 364 publications

(308 citation statements)

References 68 publications

(30 reference statements)

Supporting

Mentioning

280

Contrasting

Unclassified

Order By: Relevance

“…The · NO produced has a high affinity for cytochrome c oxidase and may serve as a reversible inhibitor of mitochondrial respiration (vide supra) preventing ischemic reperfusion injury. Xanthine oxidase, an enzyme normally responsible for reducing oxygen to O 2 ·− , is also capable of reducing nitrite to · NO (153)(154)(155)(156)(157). The maximal rate of this process is observed at low pH and low oxygen tension.…”

Section: <31>mentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

217

160

View full text Add to dashboard Cite

During the past several years, major advances have been made in understanding how reactive oxygen species (ROS) and nitrogen species (RNS) participate in signal transduction. Identification of the specific targets and the chemical reactions involved still remains to be resolved with many of the signaling pathways in which the involvement of reactive species has been determined. Our understanding is that ROS and RNS have second messenger roles. While cysteine residues in the thiolate (ionized) form found in several classes of signaling proteins can be specific targets for reaction with H 2 O 2 and RNS, better understanding of the chemistry, particularly kinetics, suggests that for many signaling events in which ROS and RNS participate, enzymatic catalysis is more likely to be involved than non-enzymatic reaction. Due to increased interest in how oxidation products, particularly lipid peroxidation products, also are involved with signaling, a review of signaling by 4-hydroxy-2-nonenal (HNE) is included. This article focuses on the chemistry of signaling by ROS, RNS, and HNE and will describe reactions with selected target proteins as representatives of the mechanisms rather attempt to comprehensively review the many signaling pathways in which the reactive species are involved. Keywords signaling; glutathione; thioredoxin; oxidants; reactive oxygen species; thiols; peroxide; nitric oxide; peroxynitrite; 4-hydroxynonenal; cysteine; hydrogen peroxide; protein tyrosine phosphatase; reactive nitrogen species; eNOS; iNOS; nNOS; soluble guanylate cyclase; cGMP; tyrosine nitration; fatty acid nitration; NO-heme; NO-metal complexes; nitrite; protein kinase C; ERK; JNK; p38MAPK; tyrosine kinase receptors; calcium OVERVIEW OF SIGNALING BY REACTIVE SPECIESUnderstanding of the roles of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE) in signaling has evolved rapidly during the last decade. This has been markedly helped by identification of the specific targets in signaling pathways. In previous reviews, we defined how ROS, H 2 O 2 in particular,

show abstract

Section: <31>mentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

217

160

View full text Add to dashboard Cite

show abstract

“…The experimental spectra were recorded with the experimental conditions indicated in Fig. 3 [17,18]. EPR spectra of NADH-reduced XD and XO were quite useful in order to define the spectral parameters of the EPR signals detected for reduced iron-sulfur centres and Mo(V) species.…”

Section: Kmentioning

confidence: 99%

“…With NADH as reducing substrate, the XD form is also more efficient than XO in catalysing the reduction of nitrite to • NO [17]. This fact is particularly relevant in vivo, since the XD form is the predominant form in vivo.…”

Section: Kmentioning

confidence: 99%

“…Their overproduction, however, can play a major role in several pathological conditions [12][13][14][15][16]. Moreover, it was recently shown that XOR can catalyse the reduction of nitrates and nitrites, giving rise to both • NO [17,18] and peroxynitrite (ONOO -) [19]. This fact further amplifies the physiological and pathological significance of XOR.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NADH oxidase activity of rat and human liver xanthine oxidoreductase: potential role in superoxide production

et al. 2007

View full text Add to dashboard Cite

To characterise the NADH oxidase activity of both xanthine dehydrogenase (XD) and xanthine oxidase (XO) forms of rat liver xanthine oxidoreductase (XOR) and to evaluate the potential role of this mammalian enzyme as an O 2•-source, kinetics and electron paramagnetic resonance (EPR) spectroscopic studies were performed. A steady-state kinetics study of XD showed that it catalyses NADH oxidation, leading to the formation of one O 2•-molecule and half a H 2 O 2 molecule per NADH molecule, at rates 3 times those observed for XO (29.2 ± 1.6 and 9.38 ± 0.31 min -1 , respectively). EPR spectra of NADHreduced XD and XO were qualitatively similar, but they were quantitatively quite different. While NADH efficiently reduced XD, only a great excess of NADH reduced XO. In agreement with reductive titration data, the XD specificity constant for NADH (8.73 ± 1.36 lM -1 min -1 ) was found to be higher than that of the XO specificity constant (1.07 ± 0.09 lM -1 min -1 ). It was confirmed that, for the reducing substrate xanthine, rat liver XD is also a better O 2•-source than XO. These data show that the dehydrogenase form of liver XOR is, thus, intrinsically more efficient at generating O 2•-than the oxidase form, independently of the reducing substrate. Most importantly, for comparative purposes, human liver XO activity towards NADH oxidation was also studied, and the kinetics parameters obtained were found to be very similar to those of the XO form of rat liver XOR, foreseeing potential applications of rat liver XOR as a model of the human liver enzyme.Keywords Xanthine oxidoreductase Á Xanthine oxidase Á Xanthine dehydrogenase Á Rat liver Á Reactive oxygen species Á NADH Abbreviations AFR Activity-to-flavin ratio AO Aldehyde oxidase EPR Electron paramagnetic resonance FAD Flavin adenine dinucleotide ROS Reactive oxygen species Sim Simulated XD Xanthine dehydrogenase XO Xanthine oxidase XOR Xanthine oxidoreductase

show abstract

“…In particular, the XO ability to catalyse the nitrate reduction has long been known [17][18][19], but only over the last years did this activity begin to be restudied [20,21]. The subsequent XO-catalysed reduction of nitrite to nitric oxide radical (NO) has also been reported over the last decade [20,[22][23][24][25][26][27][28], but it is not yet generally recognised. Interestingly, the mammalian aldehyde oxidase [29], another member of the XO family, was also recently shown to catalyse the nitrite reduction to NO [28,30].…”

Section: Introductionmentioning

confidence: 99%

Nitrite reduction by xanthine oxidase family enzymes: a new class of nitrite reductases

Maia

Moura

2010

J Biol Inorg Chem

View full text Add to dashboard Cite

Mammalian xanthine oxidase (XO) and Desulfovibrio gigas aldehyde oxidoreductase (AOR) are members of the XO family of mononuclear molybdoenzymes that catalyse the oxidative hydroxylation of a wide range of aldehydes and heterocyclic compounds. Much less known is the XO ability to catalyse the nitrite reduction to nitric oxide radical (NO). To assess the competence of other XO family enzymes to catalyse the nitrite reduction and to shed some light onto the molecular mechanism of this reaction, we characterised the anaerobic XO-and AORcatalysed nitrite reduction. The identification of NO as the reaction product was done with a NO-selective electrode and by electron paramagnetic resonance (EPR) spectroscopy. The steady-state kinetic characterisation corroborated the XO-catalysed nitrite reduction and demonstrated, for the first time, that the prokaryotic AOR does catalyse the nitrite reduction to NO, in the presence of any electron donor to the enzyme, substrate (aldehyde) or not (dithionite). Nitrite binding and reduction was shown by EPR spectroscopy to occur on a reduced molybdenum centre. A molecular mechanism of AOR-and XO-catalysed nitrite reduction is discussed, in which the higher oxidation states of molybdenum seem to be involved in oxygen-atom insertion, whereas the lower oxidation states would favour oxygenatom abstraction. Our results define a new catalytic performance for AOR-the nitrite reduction-and propose a new class of molybdenum-containing nitrite reductases.

show abstract

Reduction of Nitrite to Nitric Oxide Catalyzed by Xanthine Oxidoreductase

Cited by 364 publications

References 68 publications

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

NADH oxidase activity of rat and human liver xanthine oxidoreductase: potential role in superoxide production

Nitrite reduction by xanthine oxidase family enzymes: a new class of nitrite reductases

Contact Info

Product

Resources

About