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CYP2E1 Enzyme: Alcohol, Paracetamol, & Cancer Risk

Written by Biljana Novkovic, PhD | Last updated:

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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.

What is CYP2E1?

CYP2E1 is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body [1].

Read more about CYPs here.

Function

This enzyme metabolizes:

  • Small organic molecules such as alcohol, acetone, and pyrazole [2, 3].
  • Fatty acids, ketone bodies, and glycerol [2, 4].
  • Clinically-used drugs such as salicylic acid, halothane, isoniazid, and isoflurane [2], Tylenol (paracetamol/acetaminophen)[3], and phenobarbital [5].
  • Toxic chemicals including carbon tetrachloride and chloroform [2].
  • Cancer-causing agents present in the diet and tobacco smoke, such as nitrosamines, aniline, and benzopyrene [6, 5].
  • Environmental toxins such as benzene, and acrylamide [2].

Location

This enzyme is found in various tissues including the brain, lungs, and kidneys. It is most concentrated in the liver [7].

The enzyme is responsible for approximately 20% of alcohol metabolism in the brain [5].

The Good

CYP2E1 acts as a double-edged sword. It is responsible for the detoxification of the environmental toxins [8]. 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 [5].

The Bad

This enzyme converts alcohol to acetaldehyde, a known cancer-causing agent [9, 10]. However, the enzyme is induced only at high, chronic levels of alcohol consumption [10, 11].

CYP2E1 activity is associated with alcohol-induced liver injury in mice [9] and neurodegeneration in rats [5].

CYP2E1 deficient mice are resistant to alcohol-induced gut leakiness and liver inflammation [12].

The activity of this enzyme contributes to the damage seen in mice with diabetes, fatty liver [13], and obesity [14].

CYP2E1 deficient mice have higher insulin sensitivity and better glucose tolerance. They are also protected from weight gain and obesity [4].

This enzyme can directly generate reactive oxygen species (ROS) and increase oxidative stress in animals and cells [4, 2].

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) [15]. Basically, even you have more than two copies, they are not active.

  • RS2031920

Smokers and excessive drinkers with C/C have a higher risk of lung cancer than people with at least one T (841 subjects) [16].

rs2031920 is associated with colorectal cancer (colon cancer) (meta-analysis, 17 studies, 17,082 subjects) [17] and oral cancer risk (meta-analysis, 14 studies, 1,962 cases and 3,271 controls) [18].

  • RS3813867

C in this position increases breast cancer risk 1.8-fold in Malaysian women (431 subjects) [19].

C increases the risk of hypertension (elevated blood pressure) in men with alcohol abuse [20].

This variant increases the risk of alcoholism in men (101 subjects) [21].

  • RS3813865

rs3813865 is associated with high altitude polycythemia (increase in red blood cells) in Tibetans (194 subjects) [22].

Increasing or Decreasing CYP2E1

These increase CYP2E1:

These decrease CYP2E1:

  • Starfruit juice [26]
  • Watercress [27]
  • Propolis [28]
  • Garlic [29, 30, 31] and its component diallyl disulfide [32]
  • Green and black tea [33]
  • Resveratrol (found in grapes, blueberries, raspberries, mulberries ) [34, 35]
  • Quercetin [36, 37]
  • Piperine (found in pepper) [38]
  • Curcumin [39]
  • Phenethylisothiocyanate, found in watercress and cruciferous veggies [40]
  • Ellagic acid [41]
  • Licochalcone A, found in traditional Chinese herbal licorice [42]
  • Dandelion leaf [43]
  • Danshen (Salvia miltiorrhiza) extract [44, 45]
  • Goldenseal (Hydrastis canadensis) [46]
  • Alhagi-honey extract [47]
  • Cornus officinalis extract [47]
  • Apocynum venetum [47]
  • Clomethiazole [48]

About the Author

Biljana Novkovic

PhD
Biljana received her PhD from Hokkaido University.
Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science & health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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