Nitrate and nitrite in biology, nutrition and therapeutics

Lundberg, Jon O.; Gladwin, Mark T.; Ahluwalia, Amrita; Benjamin, Nigel; Bryan, Nathan S.; Butler, Anthony R.; Cabrales, Pedro; Fago, Angela; Feelisch, Martin; Ford, Peter C.; Freeman, Bruce Α.; Frenneaux, Michael; Friedman, Joel M.; Kelm, Malte; Kevil, Christopher G.; Kim‐Shapiro, Daniel B.; Kozlov, Andrey V.; Lancaster, Jack R.; Lefer, David J.; McColl, Kenneth E.L.; McCurry, Kenneth R.; Patel, Rakesh P.; Petersson, Joel; Rassaf, Tienush; Реутов, В. П.; Richter‐Addo, George B.; Schechter, Alan N.; Shiva, Sruti; Tsuchiya, Koichiro; Faassen, Ernst E. van; Webb, David J.; Zuckerbraun, Brian S.; Zweíer, Jay L.; Weitzberg, Eddie

doi:10.1038/nchembio.260

Cited by 516 publications

(461 citation statements)

References 42 publications

(54 reference statements)

Supporting

Mentioning

432

Contrasting

Unclassified

Order By: Relevance

“…In fact, nitrate and nitrite had long been regarded as merely inert end products of NO metabolism and of unfavourable dietary constituents. However, this ''dogma'' has been challenged by a growing number of independent studies showing that nitrite, under hypoxia and anoxia, can be reduced back to NO, in vitro, in situ and in vivo, and can act as a vasodilator, as a modulator of mitochondrial respiration and as a cytoprotector during in vivo postischaemia injury in a wide range of tissues [31][32][33][34][35]. Nitrite present in blood and other tissues has thus been viewed as an NO storage form that could be made available under conditions of hypoxia and anoxia to ensure cell survival.…”

Section: Site Of Nitrite Reductionmentioning

confidence: 99%

“…The pathways of nitrite reduction to NO, extensively reviewed recently [31][32][33][34][35], include non-enzymatic disproportionation at low pH values, reduction by deoxyhaemoglobin or myoglobin, by mitochondrial cytochromes and cytochrome P 450 , and through the enzymatic conversion by XO and aldehyde oxidase. The in vivo relative importance of each of those ''nitrite-recycling'' pathways is difficult to evaluate, because it is determined by multifactoral aspects: the molecular oxygen concentration, the cellular pH and redox state, and the tissue type (which determines the concentration of enzyme, nitrite and available reducing substrates).…”

Section: Site Of Nitrite Reductionmentioning

confidence: 99%

“…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]. This XOcatalysed and aldehyde oxidase catalysed nitrite reduction assumes particular importance owing to the amount of experimental evidence that points towards the participation of these two enzymes in the human in vivo formation of NO from nitrite (as was extensively and recently reviewed in [31][32][33][34][35]). However, in spite of these reactions being known for a while, the molecular mechanism of nitrate and nitrite reduction remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Section: Site Of Nitrite Reductionmentioning

confidence: 99%

Section: Site Of Nitrite Reductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

show abstract

“…Endogenous nitrite anions are a major intravascular storage of mammalian nitric oxide, a potent vasodilatory and signaling molecule. Even at low concentrations, nitrite regulates a number of signaling events along the (patho)physiological oxygen gradient including modulation of mitochondrial respiration and cytoprotection following ischemic insult [8][9][10][11]. Unfortunately, the actual circulating levels of nitrite in humans have been difficult to measure due to sampling problems and the poor performance of analytical assays.…”

Section: Introductionmentioning

confidence: 99%

Construction of effective disposable biosensors for point of care testing of nitrite

Monteiro

Rodrigues

Gonçalves

et al. 2015

Talanta

View full text Add to dashboard Cite

In this paper we aim to demonstrate, as a proof-of-concept, the feasibility of the mass production of effective point of care tests for nitrite quantification in environmental, food and clinical samples. Following our previous work on the development of third generation electrochemical biosensors based on the ammonia forming nitrite reductase (ccNiR), herein we reduced the size of the electrodes' system to a miniaturized format, solved the problem of oxygen interference and performed simple quantification assays in real samples. In particular, carbon paste screen printed electrodes (SPE) were coated with a ccNiR/carbon ink composite homogenized in organic solvents and cured at low temperatures. The biocompatibility of these chemical and thermal treatments was evaluated by cyclic voltammetry showing that the catalytic performance was higher with the combination acetone and a 40 °C curing temperature.The successful incorporation of the protein in the carbon ink/solvent composite, while 2 remaining catalytically competent, attests for ccNiR's robustness and suitability for application in screen printed based biosensors.Because the direct electrochemical reduction of molecular oxygen occurs when electroanalytical measurements are performed at the negative potentials required to activate ccNiR (ca. -0.4 V vs Ag/AgCl), an oxygen scavenging system based on the coupling of glucose oxidase and catalase activities was successfully used. This enabled the quantification of nitrite in different samples (milk, water, plasma and urine) in a straightforward way and with small error (1 -6%). The sensitivity of the biosensor towards nitrite reduction under optimized conditions was 0.55 A M -1 cm -2 with a linear response range 0.7 -370 µM.

show abstract

“…Orally ingested or endogenously produced nitrate is extracted from the circulation by the salivary glands and then secreted in the saliva into the oral cavity, where it is reduced to nitrite (NO 2 − ) by bacteria-expressing nitrate reductase activity (12). This nitrite-rich saliva is then swallowed and enters the blood, where it can be further reduced to NO by vascular nitrite reductases, including xanthine oxidoreductase (XOR) (13,14).…”

mentioning

confidence: 99%

Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

Khambata

Ghosh

Rathod

et al. 2017

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

Self Cite

View full text Add to dashboard Cite

Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO 3 − ) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitratefed mice there is reduced systemic leukocyte rolling and adherence, circulating neutrophil numbers, neutrophil CD11b expression, and myeloperoxidase activity compared with wild-type littermates. Moreover, we show in both the ApoE KO mice and using an acute model of inflammation that this effect upon neutrophils results in consequent reductions in inflammatory monocyte expression that is associated with elevations of the antiinflammatory cytokine interleukin (IL)-10. In summary, we demonstrate that inorganic nitrate suppresses acute and chronic inflammation by targeting neutrophil recruitment and that this effect, at least in part, results in consequent reductions in the inflammatory status of atheromatous plaque, and suggest that this effect may have clinical utility in the prophylaxis of inflammatory atherosclerotic disease.

show abstract

Nitrate and nitrite in biology, nutrition and therapeutics

Cited by 516 publications

References 42 publications

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

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

Construction of effective disposable biosensors for point of care testing of nitrite

Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

Contact Info

Product

Resources

About