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GSTM1: GST enzymes and glutathione for environmental toxins

Exposure to many different man-made chemical compounds occurs every day, and our exposure to new toxicants well exceeds what our ancestors experienced. Your body has fascinating ways of breaking down and eliminating toxicants, medications, and even hormones made in the body.

This article explains how glutathione is utilized to detoxify certain toxicants. I’ll explain the glutathione-S-transferase genes and the impact that genetic variants have on phase II detoxification.

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GSTs: phase II detoxification enzymes

The glutathione S-transferase genes code for enzymes involved in the removal of a variety of carcinogens and environmental toxins.[ref]

These phase II detoxification enzymes combine the metabolites from phase I with molecules that make them less toxic and more easily excreted.

There are eight different enzymes in the GST family of genes identified by Greek letters: alpha, kappa, mu, omega, pi, sigma, theta, and zeta. As such, abbreviations for the classes start with their first letter (i.e., GSTMA for alpha).

The GST enzymes are found in the liver, intestines, and several other tissues. They are responsible for detoxifying a large number of pesticides, herbicides, carcinogens, and chemotherapy drugs.

Glutathione, an endogenous antioxidant

The GST enzymes conjugate (bind) an antioxidant called glutathione to the substance for elimination. Glutathione is considered the master antioxidant for the body.

Once a toxic substance has been conjugated with glutathione via the GST-specific enzyme, the body excretes it via bile or urine.

Toxins neutralized by GSTs

The GST enzymes and glutathione conjugation is important in detoxifying hundreds of different environmental toxicants.  Here are just a few  examples:

  • The GST enzymes are essential in detoxifying polycyclic aromatic hydrocarbons (PAHs), which are carcinogenic. Cigarette smoke, diesel exhaust, and grilled meats all contain PAHs.[ref]
  • Aflatoxin B1, a fungal component found on grains and peanuts, is detoxified by conjugation with glutathione using GST enzymes.[ref]
  • Acrolein is an aldehyde used as a pesticide and a byproduct of tobacco smoke. It also forms when frying foods in oil at high temperatures.[ref]

Reducing oxidative stress:

In addition to their role in removing toxicants, the GST enzymes are also important for neutralizing reactive oxygen species (ROS) which cause oxidative stress in cells.[ref][ref]

Genetic variants that decrease GST enzyme function increase the susceptibility to diseases that are caused by oxidative stress, such as neurodegenerative diseases, cancers, epilepsy, and ataxia.[ref]

What happens when you have reduced GST function?

Several fairly common genetic variants can decrease the function of the GST enzymes, but with several different GST enzymes available, your body usually has a backup route for getting rid of toxicants.

Importantly, environmental factors, such as exposure to toxicants (pollution, cigarette smoke), also play a large role here. It really is a matter of genetic susceptibility along with exposure to toxins and carcinogens.

I’ll cover ways to increase GST function in the Lifehacks section.

GST Genotype Report:

Genetic variants greatly impact the way that your GST genes function, with common variants causing non-functioning genes.

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Lifehacks: Optimizing diet, supplements, and environment with GST SNPs

There are several dietary ways to naturally increase the amount of GST enzymes the body produces.

Lifestyle factors with GST variants:

Stop smoking and avoid second-hand smoke:
Studies have linked the GSTM1 null genotype with a 46% increase in the risk of lung cancer in smokers.[ref]

Avoid Radon:
People with GSTM1 null genotypes are at a 3-fold increased risk of lung cancer with radon exposure.[ref]

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Related Articles and Topics:

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How your genes influence BPA detoxification:
BPA, a chemical found in some plastics, has links to a variety of effects on people, including obesity, insulin resistance, and epigenetic effects on the fetus. Genetics plays a role in how quickly you can eliminate BPA from your body.

Nrf2 Pathway: Increasing the body’s ability to get rid of toxins
The Nrf2 (Nuclear factor erythroid 2–related factor) signaling pathway regulates the expression of antioxidants and phase II detoxification enzymes. This is a fundamental pathway that is important in how well your body functions. Your genetic variants impact how well this pathway functions.

Phase I and Phase II detoxification
Learn how the different genetic variants in phase I and phase II detoxification genes impact the way that you react to medications and break down different toxins.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.