Update of the NAD(P)H:Quinone oxidoreductase (NQO) gene family
Open accessAbstract
The NAD(P)H:quinone acceptor oxidoreductase (NQO) gene family belongs to the flavoprotein clan and, in the human genome, consists of two genes (NQO1 and NQO2). These two genes encode cytosolic flavoenzymes that catalyse the beneficial two-electron reduction of quinones to hydroquinones. This reaction prevents the unwanted one-electron reduction of quinones by other quinone reductases; one-electron reduction results in the formation of reactive oxygen species, generated by redox cycling of semiquinones in the presence of molecular oxygen. Both the mammalian NQO1 and NQO2 genes are upregulated as a part of the oxidative stress response and are inexplicably overexpressed in particular types of tumours. A non-synonymous mutation in the NQO1 gene, leading to absence of enzyme activity, has been associated with an increased risk of myeloid leukaemia and other types of blood dyscrasia in workers exposed to benzene. NQO2 has a melatonin-binding site, which may explain the anti-oxidant role of melatonin. An ancient NQO3 subfamily exists in eubacteria and the authors suggest that there should be additional divisions of the NQO family to include the NQO4 subfamily in fungi and NQO5 subfamily in archaebacteria. Interestingly, no NQO genes could be identified in the worm, fly, sea squirt or plants; because these taxa carry quinone reductases capable of one- and two-electron reductions, there has been either convergent evolution or redundancy to account for the appearance of these enzyme functions whenever they have been needed during evolution.
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The lack of NQO genes in sea urchins is in line with the observed lack of NQO genes in worm, fly, sea squirt, or plants.
“This latter finding is in line with the observed lack of NQO genes in the worm, fly, sea squirt, or plants (Vasiliou et al., 2006).”
From The chemical defensome: Environmental sensing and response genes in the Strongylocentrotus purpuratus genome (2006) · cites this paper as Vasiliou et al., 2006
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- Authors
- Vasiliou, V., Ross, D., & Nebert, D. W.
- Affiliations
- University of Colorado Health (US)
- University of Cincinnati Medical Center (US)
- Corresponding author
- Vasiliou, Vasilis
- Venue
- Human Genomics
- Published
- 2006
- Volume
- 2
- Issue
- 5
- Pages
- 329
- ISSN
- 1473-9542 (ISSN-L)
- 1479-7364
- PMC
- PMC3500182
- OpenAlex
- W2112252275
- Cited by
- 178
- References
- 40
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 7 · 2023: 4 · 2022: 10 · 2021: 10 · 2020: 13 · 2019: 7 · 2018: 8 · 2017: 7 · 2016: 14 · 2015: 8 · 2014: 12 · 2013: 10 · 2012: 9
- FWCI
- 10.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Human Genomics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (EY11490)
- National Eye Institute (R01EY011490, R01 EY11490)
- National Institute of Environmental Health Sciences (R01ES009554, P30ES006096, R01 ES09554, P30 ES-06096)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- NAD(P)H:quinone oxidoreductase, NQO1, NQO2, flavoenzyme, quinone reduction, reactive oxygen species, oxidative stress response, benzene exposure, myeloid leukemia, convergent evolution, gene family evolution
- MeSH terms
- Animals, Flavoproteins, Multigene Family, Humans, Dihydrolipoamide Dehydrogenase, Genetic Variation, NAD(P)H Dehydrogenase (Quinone), Nitric Oxide Synthase, Evolution, Molecular, NADPH Oxidases
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