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CYP2E1 is an important detox enzyme involved in the metabolism of alcohol. It also eliminates Tylenol (paracetamol). This enzyme clears toxins, but can also activate them. Its activity is associated with alcohol-related disorders and cancer. Read on to find out more about CYP2E1 function, genetics, and factors that increase or decrease enzyme activity.

CYP2E1

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CYP2E1 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body (R).

Read more about CYPs here.

CYP2E1 Function

This enzyme metabolizes:

CYP2E1 Location

This enzyme is found in various tissues including the brain, lungs, and kidneys. It is most concentrated in the liver (R).

The enzyme is responsible for approximately 20% of alcohol metabolism in the brain (R).

CYP2E1 The Good

CYP2E1 acts as a double-edged sword. It is responsible for the detoxification of the environmental toxins (R). However, it can also activate many of them.

Although some studies suggest CYP2E1 activity is implicated in Parkinson’s disease, other studies show that CYP2E1 brain activity is beneficial. This enzyme can have beneficial effects due to its efficient removal of neurotoxins related to Parkinson’s, such as metals and pesticides (R).

CYP2E1 The Bad

This enzyme converts alcohol to acetaldehyde, a known cancer-causing agent (R, R). However, the enzyme is induced only at high, chronic levels of alcohol consumption (R, R).

CYP2E1 activity is associated with alcohol-induced liver injury in mice (R) and neurodegeneration in rats (R).

CYP2E1 deficient mice are resistant to alcohol-induced gut leakiness and liver inflammation (R).

The activity of this enzyme contributes to the damage seen in mice with diabetes, fatty liver (R), and obesity (R).

CYP2E1 deficient mice have higher insulin sensitivity and better glucose tolerance. They are also protected from weight gain and obesity (R).

This enzyme can directly generate reactive oxygen species (ROS) and increase oxidative stress in animals and cells (R, R).

CYP2E1 Gene Polymorphism

There are several CYP2E1 variants that influence this enzyme’s activity.

CYP2E1 gene duplications and deletions also exist. However, these don’t have a large impact on CYP2E1 activity, because of a gene dosage compensation mechanism (unlike what happens with CYP2A6 and CYP2D6) (R). Basically, even you have more than two copies, they are not active.

Smokers and excessive drinkers with C/C have a higher risk of lung cancer than people with at least one T (841 subjects) (R).

rs2031920 is associated with colorectal cancer (colon cancer) (meta-analysis, 17 studies, 17,082 subjects) (R) and oral cancer risk (meta-analysis, 14 studies, 1,962 cases and 3,271 controls) (R).

C in this position increases breast cancer risk 1.8-fold in Malaysian women (431 subjects) (R).

C increases the risk of hypertension (elevated blood pressure) in men with alcohol abuse (R).

This variant increases the risk of alcoholism in men (101 subjects) (R).

rs3813865 is associated with high altitude polycythemia (increase in red blood cells) in Tibetans (194 subjects) (R).

Increasing or Decreasing CYP2E1

These increase CYP2E1:

These decrease CYP2E1:

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