Many CYP enzymes are essential for the detox of drugs, metabolic products, and environmental toxins. Others are necessary to produce steroid hormones and sex-related features. Some of these enzymes vary greatly due to genetics. Others vary less but are more sensitive to environmental factors, such as the food we eat. Read on to discover more about these enzymes and what it means to be a poor, extensive, or rapid metabolizer.
Cytochrome P450 monooxygenases (CYPs) are enzymes that help with the removal of most of the drugs and toxins from the human body .
They are responsible for the so-called Phase I of the detoxification process.
For example, CYPs process cancer-causing agents (such as polycyclic aromatic hydrocarbons or PAHs, aromatic amines, heterocyclic amines), pesticides, herbicides, and the vast majority of clinical drugs .
There are 57 human CYP enzymes .
Although many of the CYPs are detox enzymes, their activity can actually convert less toxic molecules into more toxic active products. These then need to be further detoxified by Phase II enzymes. For example, CYP1A1 can activate some cancer-causing agents [5, 6], while CYP2E1 can activate several liver toxins and thereby contribute to alcoholic liver damage .
That is why elevated Phase I activity is not necessarily a good thing. As Phase I enzymes produce toxic and cancer-causing compounds, they need to be in balance with Phase II enzymes.
You can read more about Phase I and II enzymes here.
Many health-boosting supplements and herbs actually decrease CYP activity, and thereby may, in theory, reduce the activation of cancer-causing agents .
Tobacco smoke, on the other hand, induces some of the CYPs .
CYP enzymes have been an important subject of focus in pharmacogenetics – that’s the study of how people respond to drug therapy based upon their genes.
Thousands of mutations in CYP genes have been described, but certain variants (SNPs) have a larger impact on enzyme activity. Variants in CYP2D6, CYP2C19, CYP2C9, CYP2B6, CYP3A5, and CYP2A6 are of particular importance [4, 9].
Based on these SNPs, people have distinct drug responses, termed as :
- Extensive (Normal)
This means that people can be classified according to the activities of particular CYP enzymes. For example, the most frequent type of CYP2D6 is the normal or so-called extensive-metabolizer. 78.8% of people are extensive CYP2D6 metabolizers. This group is followed by intermediate- (12.1%), poor (7.6%) and ultra-rapid metabolizers (1.5%) .
If you are an ultrarapid metabolizer, you can experience :
- a lack of efficacy if the drug itself is responsible for the effect. This happens because the drug gets degraded too quickly to have an effect.
- a very intense effect if the drug itself is inactive, but the CYP enzyme makes it active by processing it.
Again, if you are a poor metabolizer, you may experience:
- a stronger effect with the drug, if the drug itself is responsible for the effect.
- a weaker effect or a lack of effect if the drug needs to be processed by the CYP enzyme to be effective.
Apart from our genes, our health and the food we eat can also greatly affect CYP enzyme function.
- Polycyclic aromatic hydrocarbons (PAHs) activate Ahr, which in turn increases CYP1A and CYP1B enzymes .
- PXR is activated by small molecules such as steroids, rifampicin, and metyrapone, and then it increases CYP3A enzymes .
- CAR binds phenobarbital, orphenadrine and other drugs to activate CYP2B enzymes .
- Clofibrate and similar substances activate PPARα, which in turn activates CYP4A enzymes .
These enzymes are important for the detox of drugs and toxins. Find out more about each of the CYP enzymes by following the links below.
- CYP1A1 – removes toxins, but can also activate some cancer-causing agents.
- CYP1A2 – a key enzyme for clearing caffeine. Gene variants have a big impact on how coffee will affect our bodies.
- CYP1B1 – helps combat oxidative stress. Studies suggest lower activity of this enzyme may protect against obesity and cancer.
- CYP2A6 – helps process nicotine. There is a link between this enzyme’s activity, smoking, and lung cancer risk.
- CYP2B6 – clears clinical drugs. The gene is highly variable.
- CYP2C8 – helps clear many clinical drugs including NSAIDs (diclofenac, ibuprofen).
- CYP2C9 – clears up to 15 – 20% of all clinical drugs, including warfarin. Gene variants greatly affect the way we react to these drugs.
- CYP2C19 – helps clear about 10% of common clinical drugs, including omeprazole and Plavix. High enzyme activity has been linked to depression.
- CYP2D6 – clears 20% of clinical drugs, including codeine. This enzyme also affects dopamine and serotonin levels may affect human personality and behavior traits.
- CYP2E1 – metabolizes alcohol and eliminates Tylenol. It can both clear or activate toxins. It may play a role in alcohol-related disease and cancer.
- CYP3A4 – clears 45 – 60% of currently prescribed drugs. Different foods and supplements (such as grapefruit) can decrease CYP3A4 activity and interfere with drug metabolism.
- CYP3A5 – Do you have this enzyme? Many people don’t. In people who do have it, it helps clear over 50% of clinical drugs.
These enzymes are important because they produce steroid hormones. They affect our estrogen and testosterone levels, our blood pressure and response to stress. You can learn more about each of these CYP enzymes by following the links below.
- CYP11A1 – this enzyme is necessary for the production of all steroid hormones. It acts as an anti-inflammatory agent but may increase susceptibility to allergies.
- CYP11B2 – produces aldosterone, which helps conserve sodium. Some CYP11B2 gene variants have been associated with high blood pressure and heart disease.
- CYP17A1 – produces testosterone. Some gene variants have been linked to high blood pressure, heart disease, Alzheimer’s and cancer.
- CYP19A1 – produces estrogen and affects a variety of processes in the body, including fat production and distribution, bone density, female fertility, and brain function. Gene variants have been linked to migraines, osteoporosis, hardening of the arteries, Alzheimer’s, and estrogen-sensitive cancers.
- CYP21A2 – helps produce cortisol and aldosterone, while it lowers testosterone levels. Variants that decrease enzyme activity are fairly common. They cause more masculine traits in women and lower fertility in both sexes. However, these variants have also been associated with a lower risk of having mood and stress-related disorders.