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.

This article covers the function of the NQO1 enzyme and explains how genetic variants here can impact your risk for certain cancers.

NQO1 gene:

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

Quinones and hydroquinones:

The NQO1  gene codes for the enzyme NAD(P)H: quinone oxidoreductase 1 enzyme. This enzyme uses NADH or NADPH to reduce quinones to hydroquinones.

Quinones are usually formed in the body as intermediates - the product that occurs when the body is breaking down certain substances. These types of reactions go on all the time in the body. Because quinones are so reactive, it is important for the body to convert quinones into hydroquinones quickly.

For example, when the body breaks down estrogen for elimination, an intermediate is formed which is an estrogen quinone metabolite that is linked to breast cancer risk. NQO1 can help to metabolize and get rid of the estrogen quinone metabolites, thus decreasing cancer risk. (Estrogen metabolism article)

NQO1 is also involved in cellular defense against oxidative stress, as well as the conversion of CoQ10 and the 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].

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]

 

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 that Reduce the Function of the NQO1 gene:

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 dependent on the substance.

 


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