This is part of an ongoing series on the genes involved in detoxification.

NAD(P)H:quinone oxidoreductase 1 (abbreviated as NQO1) uses NADH or NADPH to reduce quinones to hydroquinones.   NQO1 is involved in breaking down exogenous (outside) toxins such as benzene and some chemotherapy drugs.  Benzene, a carcinogen, is found  in gasoline fumes, laundry detergent, furniture wax, industrial uses, pesticides, and smoke.

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

Two polymorphisms have been identified.  NQO1*2 leads to a deficiency in the enzyme, while NQO1*3 has reduced a enzyme activity which may depend on the substance.   Absence of NQO1 has recently been studied (in mice) and found to lead to gut impermeability and inflammation (leaky gut) [ref].

Check your 23andMe results for rs1131341:

  • AG: NQO1*3, decreased enzyme function depending on substance
  • GG: normal

 

Check your 23andMe results for rs1800566:

  • AA: NQO1*2, higher cancer risk from benzene, no NQO1 [ref]
  • AG: NQO1*1/*2, somewhat higher cancer risk from benzene, intermediate enzyme function
  • GG: normal

Researchers have found that the NQO1 enzyme can be induced by green tea extract and broccoli sprouts [ref] as well as resveratrol[ref].

From a 2002 paper in the American Journal of Clinical Nutrition:

The polymorphism results in reduced amounts of the NQO1 protein, possibly as the result of to an accelerated degradation via the ubiquitin pathway. The mutant expressed in E. coli has between 2% and 4% of the activity of the wild-type enzyme (186). The cause of both of these observations is likely to be an aberrant binding of FAD by the mutant enzyme. The Pro187→Ser mutation disturbs the structure of the central parallel β-sheet (192), resulting in a reduction in binding affinity for the FAD cofactor (193). Others found that NQO1 activity can be measured only in the presence of increased concentrations of FAD, confirming that the impairment of activity in the Pro187→Ser enzyme is due to lowered FAD affinity (Ivonne Rietjens, unpublished observations, 2001).

These data suggest that individuals with the NQO1 polymorphism might benefit from high-dose riboflavin treatment by reductions in cancer risk. Further studies should be done to verify or reject this theory.

It looks like there have been several more studies done in the past few years regarding FAD and NQO1 [ref] [ref].

More to read:

NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector  – this is a very thorough overview from 2011

Association of HMOX1 and NQO1 Polymorphisms with Metabolic Syndrome Components

Induction of the phase II detoxification enzyme NQO1 in hepatocarcinoma cells by lignans from the fruit of Schisandra chinensis through nuclear accumulation of Nrf2.

NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: A HuGE review

 


1 Comment

Genetic Lifehacks | Nrf2 Pathway · July 9, 2015 at 3:19 pm

[…] that can be excreted by the body.  Specifically, the Nrf2 signaling pathway is involved in GSTs, NQO1, UGTs, and […]

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