Abstract

ATIAA, Ahmed  and  ABDULLAH, Azman. NQO1 enzyme and its role in cellular protection; an insight. Iberoam J Med [online]. 2020, vol.2, n.4, pp.306-313.  Epub Dec 25, 2023. ISSN 2695-5075.  https://dx.doi.org/10.5281/zenodo.3877528.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is considered as one of the most significant enzyme in cellular defense due to its ability to detoxify reactive quinones and quinone imines to their less toxic hydroquinones forms. NQO1 is a xenobiotic metabolizing cytosolic enzyme that catalyzes the reduction of two- or four-electron of numerous exogenous and endogenous quinones by utilizing flavin adenine dinucleotide (FAD) as a cofactor. NQO1 enzyme exists as a homodimer enzyme and is biochemically identified by its noticeable ability to utilize either NADH or NADPH as reducing cofactors and by its inhibition by anticoagulant agents such as dicumarol. NQO1 is a distinctly inducible enzyme and known to be controlled by the Nrf2-Keap1 pathway. The importance of the antioxidant activities exhibited by NQO1 enzyme in suppressing the oxidative stress status is provided by demonstration that induction or reduction of NQO1 levels are linked with increased and reduced susceptibilities to oxidative stress, respectively. The gene coding for NQO1 has two well-recognized polymorphisms at nucleotide site 609(C-T) and 465 (C-T) of the human cDNA. C609T causes complete loss of enzymatic activity due to protein instability, whereas the C465T results in reduction of the enzyme activity. In this Review, we deliberate the protecting activates of NQO1 and discussing its possible transcriptional pathways regulating its induction by Nrf2-Keap1/ARE system.

Keywords : Gene expression; NQO1; Keap1; ARE.

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