Mechanism for the inhibition of aldehyde dehydrogenase by nitric oxide

DeMaster, Eugene G.; Redfern, Beth; Quast, Barry J.; Dahlseid, Todd; Nagasawa, Hiromichi

doi:10.1016/s0741-8329(96)00142-5

Cited by 37 publications

(32 citation statements)

References 46 publications

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“…The latter is especially important, because nucleophilic addition to HNO is proposed to occur in the degradation of S-nitrosothiols in the presence of added thiol, to yield the corresponding sulfinamide and ultimately, NH 3 (9). The mechanism of aldehyde dehydrogenase inhibition is also thought to involve attack of the activesite sulfhydryl group at nitrogen of HNO (18,19).…”

Section: Dimerization and Reactivity Toward Nucleophilesmentioning

confidence: 99%

“…HNO has biological activity; it can act as a potent cytotoxic agent that causes double-stranded breaks in DNA, depletion of cellular glutathione (16), as well as elicitation of smooth muscle relaxation (17). HNO has been found to be a potent inhibitor of thiol-containing enzymes (18,19) and attenuates the activity of the NMDA receptor via thiol modification, thus providing neuroprotection (20).Much of the fundamental biological chemistry associated with HNO is unknown, aside from the rate constant for dimerization is a typical nucleophile, yet several studies find that HNO generated at physiological pH reacts readily as an electrophile, particularly with thiols, to yield N-hydroxysulfenamide intermediates (9, 21), implying a higher pK a . NO Ϫ and NO react rapidly and irreversibly to form N 2 O 2 Ϫ , a reactive radical anion (6).…”

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On the acidity and reactivity of HNO in aqueous solution and biological systems

Bartberger

Fukuto

Houk

2001

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

163

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The gas phase and aqueous thermochemistry and reactivity of nitroxyl (nitrosyl hydride, HNO) were elucidated with multiconfigurational self-consistent field and hybrid density functional theory calculations and continuum solvation methods. The pK a of HNO is predicted to be 7.2 ؎ 1.0, considerably different from the value of 4.7 reported from pulse radiolysis experiments. The ground-state triplet nature of NO ؊ affects the rates of acid-base chemistry of the HNO͞NO ؊ couple. HNO is highly reactive toward dimerization and addition of soft nucleophiles but is predicted to undergo negligible hydration (Keq ‫؍‬ 6.9 ؋ 10 ؊5 ). HNO is predicted to exist as a discrete species in solution and is a viable participant in the chemical biology of nitric oxide and derivatives.T he discoveries of nitric oxide (NO) biosynthesis in mammalian cells and the diverse biological activity associated with NO and NO-derived species (1) have brought intense interest in the physiological chemistry of nitrogen oxides. The chemistry of NO and its biologically accessible oxidized congeners nitrogen dioxide (NO 2 ), nitrite (NO 2 Ϫ ), peroxynitrite (ONOO Ϫ ), dinitrogen trioxide (N 2 O 3 ), and nitrate (NO 3 Ϫ ) is fairly well established (2). By contrast, the reduced congeners such as nitroxyl (HNO) and its conjugate base (NO Ϫ ) are less well understood, and consequently their role in biology is not clear. The importance of HNO or NO Ϫ in biology has often been neglected or dismissed, in part because NO metabolism is thought to be primarily oxidative in nature (3), and because HNO is thought to be only metastable (3), a strong acid (4), and to dimerize readily (5). NO Ϫ is known to react rapidly and irreversibly with NO (6), making the examination of NO Ϫ in the presence of NO difficult. Additionally, HNO might be expected to be electrophilic, and hydration under physiological conditions would serve to attenuate its aqueous reactivity.Nitroxyl (HNO), or its conjugate base, NO Ϫ , is known to be formed under physiological conditions; for example, oxidation of N-hydroxy-L-arginine (an intermediate in NO biosynthesis) (7), reaction of S-nitrosothiols with thiols (8, 9), nitric oxide synthase (10-12), and even direct reduction of NO by mitochondrial cytochrome c (13), may all generate HNO. Nitroxyl has been generated via the interaction of NO with manganese superoxide dismutase (14) and with ubiquinol (15). HNO has biological activity; it can act as a potent cytotoxic agent that causes double-stranded breaks in DNA, depletion of cellular glutathione (16), as well as elicitation of smooth muscle relaxation (17). HNO has been found to be a potent inhibitor of thiol-containing enzymes (18,19) and attenuates the activity of the NMDA receptor via thiol modification, thus providing neuroprotection (20).Much of the fundamental biological chemistry associated with HNO is unknown, aside from the rate constant for dimerization is a typical nucleophile, yet several studies find that HNO generated at physiological pH reacts readily as an electrophile, par...

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Section: Dimerization and Reactivity Toward Nucleophilesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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On the acidity and reactivity of HNO in aqueous solution and biological systems

Bartberger

Fukuto

Houk

2001

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

163

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“…Further, S-nitrosation of thiols is postulated to induce several functional protein modifications in vivo (13)(14)(15)(16)(17)(18). In addition to thiols, secondary amines also react rapidly with N 2 O 3 (7).…”

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confidence: 99%

Regiospecific Nitrosation of N-terminal-blocked Tryptophan Derivatives by N2O3 at Physiological pH

Kirsch¹,

Fuchs²,

Groot

2003

Journal of Biological Chemistry

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Nitric oxide ( ⅐ NO) is involved in a great variety of physiological and pathophysiological processes, including the regulation of vascular tonus, immune response, and neurotransmission (1). In mammals the basal level of ⅐ NO (in the aqueous phase) is in the nanomolar range (2). However, the local ⅐ NO concentrations can be increased substantially in areas with high NO synthase activity and/or in hydrophobic regions (3, 4), thereby facilitating the formation of dinitrogen trioxide (N 2 O 3 ) (Equations 1 (5) and 2 (6)).2 ⅐ NO ϩ O 2 3 2 ⅐ NO 2 k 1 ϭ 2.9 ϫ 10 6 M Ϫ2 s Ϫ1

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“…), desde que estes últi-mos possam ser liquefeitos ou que sejam pastosos, de modo a possibilitar a imersão do biossensor na matriz, e proceder ao ensaio de inibição conforme descrito anteriormente. A literatura registra outros inibidores da AldH, tais como dissulfiram e metabólitos 41 e cinamida 42 (compostos usados clinicamente para tratamento do alcoolismo); prunetina 43 (um derivado de isoflavonóides); óxido nítrico 44 ; metilglioxal 45 e ampal 46 (metabólitos de alguns processos bioquímicos que ocorrem no fígado de mamíferos), entre outros. A possibilidade de resíduos de tais compostos serem encontrados em amostras ambientais ou nos alimentos é praticamente nula, o que torna improvável a interferência no sistema biossensor proposto.…”

Section: Avaliação Da Estabilidade Operacional Do Biossensorunclassified

Biossensor enzimático para detecção de fungicidas ditiocarbamatos: estudo cinético da enzima aldeído desidrogenase e otimização do biossensor

Lima¹,

Nunes²,

Noguer³

et al. 2007

Quím. Nova

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Recebido em 13/7/05; aceito em 3/4/06; publicado na web em 11/8/06 ENZYMATIC BIOSENSOR FOR THE DETECTION OF DITHIOCARBAMATE FUNGICIDES. KINETIC STUDY OF ALDEHYDE DEHYDROGENASE ENZYME AND BIOSENSOR OPTIMIZATION. Initially, all major factors that affect the rate of the AldH-catalyzed reaction (enzyme concentration, substrate concentration, temperature and pH) were investigated. Optimal activity was observed between pH values of 7.5 and 9.5 in the temperature range of 25 to 50 o C. Kinetic parameters, such as K m (2.92 μmol L -1 ) and V max (1.33 10 -2 μmol min -1 ) demonstrate a strong enzyme-substrate affinity. The sensors were based on screen-printed electrodes modified with the Meldola BlueReinecke salt (MBRS) combination. Operational conditions (NAD + and substrate contents, enzyme loading and response time) were optimized. Also, two enzyme immobilization procedures were tested: entrapment in poly(vinyl alcohol) bearing styrylpyridinium groups (PVA-SbQ) and crosslinking with glutaraldehyde. Chronoamperometry was employed to observe the biosensor responses during enzymatic hydrolysis of propionaldehyde and also to construct inhibition curves with maneb and zineb fungicides. Best results were found with the following conditions:; enzyme loading = 0.8 U per electrode; response time = 10 min, and inhibition time = 10 min. Current intensities around 103 ± 13 nA with the sensors and good stability was obtained for both immobilization procedures. Detection limits, calculated using 10% inhibition were 31.5 μg L -1 and 35 μg L -1 for maneb and zineb, respectively. Results obtained with other MBRS-modified electrodes consisting of mono and bi-enzymic sensors were compared. The ability to catalyze NADH oxidation by MB was also highlighted.Keywords: AldH-based biosensors; dithiocarbamate fungicides; enzymatic kinetic. INTRODUÇÃOA investigação dos pesticidas constitui um caso delicado. A necessidade de analisar resíduos de pesticidas depara-se com problemas analíticos complexos, devido à gama de substâncias existentes em classes distintas e que devem ser determinadas em diferentes tipos de matrizes, sejam elas ambientais ou de alimentos 1 . Entre os agrotóxicos mais difundidos atualmente, encontram-se os fungicidas ditiocarbamatos (DTC's). Tais compostos formam a mais importante classe de pesticidas empregados no controle de diversas doenças fungais em sementes, frutos e vegetais. Embora a toxidade aguda dos DTC's seja relativamente baixa, existe uma urgente necessidade de se encontrar um método de detecção sensível, confiável, e que permita rápidas tomadas de decisão, no caso de intoxicação em trabalhadores rurais e/ou contaminação ambiental ou alimentar. Isto devido ao fato de que, dependendo dos compostos encontrados, estes podem vir a ser carcinogênicos 2 , goitrogênicos 2 , mutagênicos 3-5 , teratogênicos 3,6,7 , provocar distúrbios neurológicos 8 e, também, afetar a biota aquática 9 . Há uma grande preocupação com relação a certos compostos como, por ex., os fungicidas maneb e ditane, que contêm manganês, precursor d...

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Mechanism for the inhibition of aldehyde dehydrogenase by nitric oxide

Cited by 37 publications

References 46 publications

On the acidity and reactivity of HNO in aqueous solution and biological systems

On the acidity and reactivity of HNO in aqueous solution and biological systems

Regiospecific Nitrosation of N-terminal-blocked Tryptophan Derivatives by N2O3 at Physiological pH

Biossensor enzimático para detecção de fungicidas ditiocarbamatos: estudo cinético da enzima aldeído desidrogenase e otimização do biossensor

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