The third melatonin binding site MT turned out to be an enzyme, NQO2 (E.C. 1.6.99.2). Its catalytic activity is inhibited by melatonin with an IC in the 50-100 μM range. Some of the functions of melatonin at pharmacological concentrations (1 μM and above) might be explained by this inhibition capacity of melatonin at NQO2. In order to determine precisely these parameters, it is required to comprehend the basic enzymology of this enzyme. In the following chapter, we present the basic conditions of measuring NQO2 catalytic activities and inhibition.
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Evolutionary analysis of Quinone Reductases 1 and 2 suggests that NQO2 evolved to function as a pseudoenzyme.
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Department of Biochemistry, University of Western Ontario, London, Ontario, Canada.
Quinone reductases 1 and 2 (NQO1 and NQO2) are paralogous FAD-linked enzymes found in all amniotes. NQO1 and NQO2 have similar structures, and both catalyze the reduction of quinones and other electrophiles; however, the two enzymes differ in their cosubstrate preference. While NQO1 can use both redox couples NADH and NADPH, NQO2 is almost inactive with these cosubstrates and instead must use dihydronicotinamide riboside (NRH) and small synthetic cosubstrates such as N-benzyl-dihydronicotinamide (BNAH) for efficient catalysis.
View Article and Find Full Text PDFMeasuring the NQO2: Melatonin Complex by Native Nano-Electrospray Ionization Mass Spectrometry.
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Laboratoire de Spectrométrie de Masse BioOrganique, Université de Strasbourg, CNRS, Strasbourg, France.
Melatonin exerts its effects through a series of target proteins/receptors and enzymes. Its antioxidant capacity might be due to its capacity to inhibit a quinone reductase (NQO2) at high concentration (50 μM). Demonstrating the existence of a complex between a compound and a protein is often not easy.
View Article and Find Full Text PDFMeasurement of NQO2 Catalytic Activity and of Its Inhibition by Melatonin.
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The third melatonin binding site MT turned out to be an enzyme, NQO2 (E.C. 1.
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Front Pharmacol
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Department of Biochemistry, University of Western Ontario, London, ON, Canada.
Article Synopsis
- NQO2 is a pharmacological target that interacts with kinase-targeted drugs, but its cellular functions remain unclear.
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Reduction and Scavenging of Chemically Reactive Drug Metabolites by NAD(P)H:Quinone Oxidoreductase 1 and NRH:Quinone Oxidoreductase 2 and Variability in Hepatic Concentrations.
Chem Res Toxicol
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AIMMS-Division of Molecular Toxicology, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.
Detoxicating enzymes NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) catalyze the two-electron reduction of quinone-like compounds. The protective role of the polymorphic NQO1 and NQO2 enzymes is especially of interest in the liver as the major site of drug bioactivation to chemically reactive drug metabolites. In the current study, we quantified the concentrations of NQO1 and NQO2 in 20 human liver donors and NQO1 and NQO2 activities with quinone-like drug metabolites.
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