Quinoneimines as substrates for quinone reductase (NAD(P)H : (Quinone-acceptor)oxidoreductase) and the effect of dicumarol on their cytotoxicity

Powis, Garth; See, Kevin Lee; Santone, Kenneth S.; Melder, Deborah C.; Hodnett, Ernest M.

doi:10.1016/0006-2952(87)90519-3

Cited by 43 publications

(14 citation statements)

References 29 publications

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“…N-acetyl-p-benzoquinoneimine, N,N-dimethylindoaniline) were shown to be substrates for NQO1, although substrate inhibition is reported at higher concentrations [43]. Consistent with the hypothesis that QRs are part of an enzymatic detoxification system, several other substrates, such as nitro-aromatic compounds [44], azodyes and ferric iron [45] have been identified (see above) [12, 46 -48].…”

Section: Reaction Mechanismmentioning

confidence: 70%

Flavin-dependent quinone reductases

Deller

Macheroux

Sollner

2007

Cell. Mol. Life Sci.

102

126

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Quinones are abundant cyclic organic compounds present in the environment as well as in pro- and eukaryotic cells. Several species have been shown to possess enzymes that afford the two-electron reduction to the hydroquinone form in an attempt to avoid the generation of one-electron reduced semiquinone known to cause oxidative stress. These enzymes utilize a flavin cofactor, either FMN or FAD, to transfer a hydride from an electron donor, such as NAD(P)H, to a quinone substrate. This family of flavin-dependent quinone reductases shares a flavodoxin-like structure and reaction mechanism pointing towards a common evolutionary origin. Recent studies of their physiological functions in eukaryotes suggest a role beyond detoxication of quinones and involvement in the oxygen stress response. Accordingly, mammalian quinone reductases emerge as central molecular switches that control the lifespan of transcription factors, such as p53, and hence participate in the development of apoptosis and cell transformation.

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Section: Reaction Mechanismmentioning

confidence: 70%

Flavin-dependent quinone reductases

Deller

Macheroux

Sollner

2007

Cell. Mol. Life Sci.

102

126

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“…Interestingly, quinoneimines are also substrates for mammalian NQOs. 26,58 It should also be noted that the quinoneimine moiety of the hydrazone tautomer of balsalazide (Fig. 4) is chemically similar to a quinone that is a substrate for several azoreductases; 10,12,17,59 thus, paAzoR1 may have a quinone oxidoreductase activity.…”

Section: Reduction Mechanism For Azo Compoundsmentioning

confidence: 97%

A Novel Mechanism for Azoreduction

Ryan

Laurieri

Westwood

et al. 2010

Journal of Molecular Biology

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“…It is well established that in addition to the inhibition of DT-diaphorase, dicoumarol has other effects on the metabolism of xenobiotics. Thus, Powis et al (1987) reported diverse effects of dicoumarol on the cytotoxicity of three yuinoneimines, suggesting that it has cellular effects other than inhibition of the DT-diaphorase. Mays and Benson (1992) also demonstrated that dicoumarol potently inhibits GSH transferase (EC 2.5.1.18) and GSH peroxidase 11.…”

Section: Discussionmentioning

confidence: 99%

“…INTRODUCTION NAD(P)H:(quinone acceptor) oxidoreductase (E.C. 1.6.99.21, also known as DT-diaphorase, is a flavoprotein catalyzing the two-electron reduction of various quinones, quinoneimines, and azo compounds (Ernster, 1987;Powis et al, 1987). This enzyme is very well characterized in mammals where it plays an important role in protecting cells by preventing the toxicity and carcinogenic activity of quinones (Lind et al, 1982).…”

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confidence: 99%

Induction of diaphorase‐1 by dicoumarol in Drosophila virilis larvae

Georgieva

Jankulova

Ralchev

et al. 1995

Arch Insect Biochem Physiol

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Drosophila diaphorase-1 (DIA-1) is an enzyme similar to mammalian DT-diaphorase and is inhibited in vitro by dicoumarol. However, a ten-fold increase in DIA-1 activity was observed when third instar Drosophila virilis larvae were fed on a diet containing 0.1 M dicoumarol for 48 h. This induction was shown to be dose dependent and immunoprecipitation experiments with DIA-1 anti-serum demonstrated an increase in the DIA-1 protein level in dicoumarol-treated larvae. The induction of DIA1 by dicoumarol was found to be blocked by actinomycin D, which suggests a transcriptional mechanism of regulation. The opposite effect of dicoumarol on DIA-1 in vitro vs. in vivo suggests that a metabolic conversion takes place after the ingestion of this compound by D. virilis larvae.

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Quinoneimines as substrates for quinone reductase (NAD(P)H : (Quinone-acceptor)oxidoreductase) and the effect of dicumarol on their cytotoxicity

Cited by 43 publications

References 29 publications

Flavin-dependent quinone reductases

Flavin-dependent quinone reductases

A Novel Mechanism for Azoreduction

Induction of diaphorase‐1 by dicoumarol in Drosophila virilis larvae

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