The CYP Enzymes: An Introduction
The Cytochromes P450 (CYPs) are a group of enzymes that play an important role in the detoxification process. Detoxification is a process by which toxins and unwanted substances are removed from the body. There are three stages of detoxification, and CYPs help in phase 1 detoxification.
According to the Human Genome Project, 57 different types of CYP enzymes are identified in human beings.
The CYP1 group of enzymes is a major part of the CYP family. The Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) is one of the three CYP1 enzymes that help in detoxification. This enzyme is majorly found in the lungs.
The CYP1A1 gene helps produce the CYP1A1 enzymes.
What Compounds Does The CYP1A1 Gene Act On?
Xenobiotic Substances
Xenobiotic substances are those that reach the body from external sources. These are not produced or found internally. The CYP1A1 enzymes work on removing Polycyclic Aromatic Hydrocarbons (PAHs) from the body.
PAHs are groups of chemicals found throughout the environment, in the air, soil, and water. PAHs are produced when fossil fuels like coal, gasoline, and oil are burnt.
These are also produced when tobacco and wood are burnt. PAHs are common toxins in charred and burnt meat. There are hundreds of PAHs in the atmosphere. Few common ones are:
- Naphthalene
- Biphenyl
- Fluorene
- Triphenylene
- Benzo[a]pyrene
- Benzo[c]fluorene
Endogenous Substances
Endogenous substances are those that are produced or available in the body. The CYP1A1 enzyme helps in the metabolism of certain endogenous substances.
Polyunsaturated Fatty Acids or PUFAs
The CYP1A1 enzyme converts PUFAs into signaling molecules. These signaling molecules are needed for various bodily functions.
CYP1B1 enzyme converts arachidonic acid, a type of PUFA, into 19-hydroxyeicosatetraenoic acid (19-HETE). 19-HETE controls high blood pressure and the growth of cancer cells.
17β-estradiol
CYP1A1 enzymes play a role in 17β-estradiol metabolism. 17β-estradiol is an estrogen hormone. This is responsible for regulating the female reproductive system.
Oxidative Stress
Oxidative stress is a condition where the number of free radicals in the body is higher than the number of antioxidants. This imbalance leads to cell damage and an increased risk of cancer and other diseases. Some studies show that the CYP1A1 enzymes fight against Reactive Oxygen Species (ROS) and prevent oxidative stress.
CYP1A1 Gene Changes (Variations) and Detoxification
Multiple changes or variations in the CYP1A1 gene lead to increased or decreased CYP1A1 enzyme activity. These gene variations protect against or increase the risk of conditions like cancer, PolyCystic Ovary Syndrome (PCOS), and diabetes.
| Haplotype | Effect | Implication |
| CYP1A1*2C | Increased enzyme activity | CYP1A1 enzyme at higher levels can accelerate phase 1 detoxification and result in increased production of free radicals. |
| CYP1A1*2A | Increased enzyme activity | CYP1A1 enzyme at higher levels can accelerate phase 1 detoxification and result in increased production of free radicals. |
Recommendations For Maintaining Healthy CYP1A1 Enzyme Levels
Antioxidants Consumption
Overactive CYP1A1 enzymes can result in free radical damage. This can be treated with an antioxidant-rich diet. The following are some great sources of antioxidants:
– Berries
– Fresh fruits and vegetables
– Nuts and seeds
– Chocolates
– Spices and herbs
Quit Smoking
The Polycyclic Aromatic Hydrocarbons (PAHs) in tobacco in cigarettes increase CYP1A1 enzyme levels. Overactivity of the enzyme leads to quick phase 1 detoxification and increased free radical damage in the body. Quit smoking to bring down the risk of cancers and other diseases.
Genetic Testing
CYP1A1 genetic testing can help you identify changes in your CYP1A1 gene. This can give some insights into your CYP1A1 enzyme levels. If you have increased levels of this enzyme, your doctor may ask you to get screened for different types of cancers frequently. A genetic counselor can also help you interpret the report and understand it better.
Summary
1. The Cytochromes P450 (CYPs) enzymes play a role in phase 1 detoxification. CYP1A1 is one of the important enzymes in this group.
2. The CYP1A1 enzyme helps with the metabolism of toxins like Polycyclic Aromatic Hydrocarbons (PAHs) and certain hormones and fatty acids in the body.
3. Certain changes in the CYP1A1 gene can increase the activity of the CYP1A1 enzyme. As a result, the phase 1 detoxification stage occurs quickly, increasing free radical molecules in the body.
4. Free radicals can damage DNA and lead to an increased risk of many types of cancer, including breast, biliary, and lung cancer.
5. Including an antioxidant-rich diet plan can help prevent free radical damage.
6. In people with high CYP1A1 enzyme levels, smoking can increase the risk of free radical damage and can cause cancers in the breast, lungs, liver, and cervix.
7. Genetic testing can give you insights into your CYP1A1 enzyme levels. For people with errors in the CYP1A1 gene, regular screening of cancer is recommended.
References
- https://www.annualreviews.org/doi/pdf/10.1146/annurev.nu.11.070191.001041
- https://www.hindawi.com/journals/jnme/2015/760689/
- https://www.sciencedirect.com/topics/medicine-and-dentistry/cytochrome-p450-1a
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1890999/
- https://pubmed.ncbi.nlm.nih.gov/29595663/
- https://pubmed.ncbi.nlm.nih.gov/28433806/
- https://pubmed.ncbi.nlm.nih.gov/19307236/
- https://pubmed.ncbi.nlm.nih.gov/25886559/
- https://pubmed.ncbi.nlm.nih.gov/23055196/
- https://pubmed.ncbi.nlm.nih.gov/26838255
- https://pubmed.ncbi.nlm.nih.gov/19632247/
