NQO1 Gene: Metabolism of quinones, benzene, and more

Your genes code for the enzymes that break down the toxic substances that we all encounter each day. This ability to clear out potential carcinogens is important when it comes to preventing cancer.

The NQO1 gene codes for an enzyme that breaks down quinones, benzene, and some chemotherapy drugs.

If you think back to high school chemistry, you may remember redox reactions – where the reactants either lost or gained an electron. NQO1 is acting as a reducing agent, which is important in the body’s ability to make certain substances easier to eliminate.

NQO1 (which is codes for the enzyme NAD(P)H: quinone oxidoreductase 1) uses NADH or NADPH to reduce quinones to hydroquinones. These types of reactions go on all the time in the body. One example is that NQO1 can help to metabolize and get rid of the estrogen quinone metabolites that increase the risk of breast cancer. (Estrogen metabolism article)

NQO1 is also involved in breaking down outside toxins such as benzene and some chemotherapy drugs. Benzene is a carcinogen found in gasoline fumes, laundry detergent, furniture wax, industrial uses, pesticides, and smoke. Benzene is also a component of smog. [ref][ref]

NQO1 is also involved in cellular defense against oxidative stress, as well as the conversion of CoQ10 and conversion of vitamin K.   In the reduction (chemistry meaning, think redox reaction) of Vitamin K, NQO1 is mostly involved in turning vitamin K3 into the form that is active in blood clotting and bone building[ref].

Additionally, NQO1 is important in the process that a cell goes through to divide and create a new cell. NQO1 has been shown to interact with NAD+ and SIRT2 during cell division. [ref]  (Read more about NAD+)

Animal studies show that a non-functioning NQO1 gene leads to gut impermeability and inflammation (leaky gut) [ref].


Genetic Variants:

Research shows there are two common NQO1 variants that reduce the function and increase the risk for certain cancers. The variant NQO1*2 (P187S) leads to a deficiency in the enzyme, while the NQO1*3 (R139W) variant has reduced enzyme activity, which may be dependant on the substance.

Check your genetic data for rs1800566 (23andMe v4, v5; AncestryDNA):

  • A/A:  NQO1 *2 – non-functioning NQO1, higher risk of cancer from benzene[ref] increased risk of lung cancer in smokers[ref] increased risk of Parkinson’s from pesticide exposure[ref], increased risk of cataracts for outdoor workers[ref]
  • A/G: intermediate enzyme function, higher risk of cancer from benzene, increased risk of Parkinson’s from pesticide exposure, increased risk of cataracts
  • G/G: normal function

Check your genetic data for rs1131341 (23andMe v4 only):

  • A/A: slightly decreased enzyme function, NQO1*3[ref][ref]
  • A/G: decreased NQO1 function
  • G/G: normal

 


Lifehacks:

What can you do if you have poor NQO1 function? There are several natural substances that may boost the function.

Riboflavin:
FAD (flavin adenine-dinucleotide) is a cofactor for NQO1, so ensuring that you get enough riboflavin (vitamin B2) in your diet or through supplements may be important. One study showed that increasing riboflavin will mitigate the negative effects of the NQO1 variant.[ref]

Riboflavin-rich foods include eggs, organ meats, dairy, and some green vegetables. [ref] If you don’t get enough riboflavin for food, it is available as a stand-alone riboflavin supplement or as part of a B-complex. (It is what causes your pee to turn bright yellow after taking a B-complex)

Other natural NQO1 boosters:
Researchers have found that the NQO1 enzyme can be induced by green tea extract and broccoli sprouts [ref]  Broccoli sprout extract is available at your local health food store or on Amazon as supplements. Alternatively, you could always just sprout broccoli seeds and eat the sprouts. They are really easy and quick to sprout.

Resveratrol has also been shown to increase NQO1 activity[ref]. Supplemental resveratrol is available at your local health food store or on Amazon. No, you can’t drink enough wine in one day to get sufficient resveratrol…

More to read:

Originally published on May 2015. Revised and updated Sept. 2019.


References:

Fong, Chin-Shih, et al. “Pesticide Exposure on Southwestern Taiwanese with MnSOD and NQO1 Polymorphisms Is Associated with Increased Risk of Parkinson’s Disease.” Clinica Chimica Acta; International Journal of Clinical Chemistry, vol. 378, no. 1–2, Mar. 2007, pp. 136–41. PubMed, doi:10.1016/j.cca.2006.11.006.

Gong, Xing, et al. “Quinone Oxidoreductases and Vitamin K Metabolism.” Vitamins and Hormones, vol. 78, 2008, pp. 85–101. PubMed, doi:10.1016/S0083-6729(07)00005-2.
Hsieh, Tze-chen, et al. “Induction of Quinone Reductase NQO1 by Resveratrol in Human K562 Cells Involves the Antioxidant Response Element ARE and Is Accompanied by Nuclear Translocation of Transcription Factor Nrf2.” Medicinal Chemistry (Shariqah (United Arab Emirates)), vol. 2, no. 3, May 2006, pp. 275–85.

Medina-Carmona, Encarnación, et al. “Conformational Dynamics Is Key to Understanding Loss-of-Function of NQO1 Cancer-Associated Polymorphisms and Its Correction by Pharmacological Ligands.” Scientific Reports, vol. 6, Feb. 2016. PubMed Central, doi:10.1038/srep20331.

Megarity, Clare F., and David J. Timson. “Cancer-Associated Variants of Human NQO1: Impacts on Inhibitor Binding and Cooperativity.” Bioscience Reports, vol. 39, no. 9, Sept. 2019. PubMed Central, doi:10.1042/BSR20191874.

Moran, Julie L., et al. “A Potential Mechanism Underlying the Increased Susceptibility of Individuals with a Polymorphism in NAD(P)H:Quinone Oxidoreductase 1 (NQO1) to Benzene Toxicity.” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 14, July 1999, pp. 8150–55.

Nam, Seung Taek, et al. “Role of NADH: Quinone Oxidoreductase-1 in the Tight Junctions of Colonic Epithelial Cells.” BMB Reports, vol. 47, no. 9, Sept. 2014, pp. 494–99. PubMed Central, doi:10.5483/BMBRep.2014.47.9.196.

Office of Dietary Supplements – Riboflavin. https://ods.od.nih.gov/factsheets/Riboflavin-Consumer/. Accessed 25 Sept. 2019.
Pey, Angel L., et al. “FAD Binding Overcomes Defects in Activity and Stability Displayed by Cancer-Associated Variants of Human NQO1.” Biochimica Et Biophysica Acta, vol. 1842, no. 11, Nov. 2014, pp. 2163–73. PubMed, doi:10.1016/j.bbadis.2014.08.011.

Ross, David, et al. “Benzene Toxicity: The Role of the Susceptibility Factor NQO1 in Bone Marrow Endothelial Cell Signaling and Function.” Chemico-Biological Interactions, vol. 192, no. 1–2, June 2011, pp. 145–49. PubMed Central, doi:10.1016/j.cbi.2010.10.008.
Siegel, David, et al. “Redox Modulation of NQO1.” PLoS ONE, vol. 13, no. 1, Jan. 2018. PubMed Central, doi:10.1371/journal.pone.0190717.

Tan, Xiang-Lin, et al. “Candidate Dietary Phytochemicals Modulate Expression of Phase II Enzymes GSTP1 and NQO1 in Human Lung Cells.” The Journal of Nutrition, vol. 140, no. 8, Aug. 2010, pp. 1404–10. PubMed Central, doi:10.3945/jn.110.121905.

US EPA, OAR. “Smog, Soot, and Other Air Pollution from Transportation.” US EPA, 10 Sept. 2015, https://www.epa.gov/transportation-air-pollution-and-climate-change/smog-soot-and-local-air-pollution.

Yamamoto, Yuzo, et al. “Biological Interaction of Cigarette Smoking on the Association between Genetic Polymorphisms Involved in Inflammation and the Risk of Lung Cancer: A Case-Control Study in Japan.” Oncology Letters, vol. 13, no. 5, May 2017, pp. 3873–81. PubMed, doi:10.3892/ol.2017.5867.

Zarei, Narjes, et al. “The Relationship between NQO1 C609T and CAT C-262Tgenetic Polymorphisms and the Risk of Age-Related Cataracts.” Molecular Biology Research Communications, vol. 4, no. 3, Sept. 2015, pp. 143–49.



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