The CYP2B6 enzyme is a part of the Cytochrome P450 (CYPs) family. The CYP family is a group of enzymes that play a major role in detoxification in the body.
The CYP enzymes help in the metabolism and clearance of the various endogenous (produced internally) and exogenous (produced externally) substances.
The CYP2B6 is expressed in the liver and accounts for 2-10% of the total CYP content in the body.
Initially, scientists believed this enzyme only had a limited role in drug metabolism.
Metabolism is the process by which large and complex food molecules and medicines are broken down into smaller components to produce energy, build or repair body tissues, produce hormones, and do more such activities needed for the body.
The CYP2B6 enzyme plays a very big role in detoxification and drug metabolism. In the list of top 200 prescription drugs sold in the United States, about 4% of them are eliminated by the CYP2B6 enzyme.
CYP2B6 and Immunity to Herbicides
In a 2005 study, researchers introduced the CYP2B6 gene into Oryza sativa cv. Nipponbare, a rice variety that has been genetically modified. As the plants grew, the scientists found that the plants were immune to 13 out of 17 herbicides (substances used to kill unwanted vegetation).
The study suggests that this CYP2B6 rice variant will grow to be more herbicide tolerant and also reduce the impact of agrochemicals (chemicals used in agriculture) on the environment.
Substances that the CYP2B6 gene act on
Nicotine
10% of nicotine metabolism is carried out by the CYP2B6 enzyme.
Chemotherapeutics
Chemotherapeutics are drugs used for chemotherapy (cancer treatment). The following chemotherapeutics are metabolized by the CYP2B6 enzyme.
- Cyclophosphamide
- Ifosfamide
- Tamoxifen
Anti-inflammatory Drugs
Anti-inflammatory drugs are prescribed to fight inflammation. These are available as both prescription and over-the-counter medications. The following anti-inflammatory drugs are cleared out by this enzyme.
- Antipyrine
- Aminopyrine
- Tazofelone
Anesthetics
Anesthetics are used in both major and minor surgeries and medical procedures to prevent patients from feeling pain during surgery. The following anesthetics are cleared by the CYP2B6 enzyme.
- Ketamine
- Propofol
- Ropivacaine
- Lidocaine
- Sevoflurane
Psychotropic drugs
Psychotropic drugs work by increasing or decreasing the level of brain chemicals. Antidepressants, anti-anxiety medication, antipsychotics, stimulants, and mood enhancers are all parts of psychotropic drugs. The following psychotropic drugs are cleared by the CYP2B6 enzyme.
- Bupropion
- Diazepam
- Temazepam
- Clotiazepam
- Midazolam
Hormones
Excess hormones like estrone (E1) and testosterone are both cleared by the CYP2B6 enzyme.
Other classes of drugs metabolized by the CYP2B6 enzyme include:
- Opioids (pain medications)
- Antiretrovirals (medications for HIV)
- Anti-epileptic medications (medications for seizures)
- Anti-malarial medications (medications to treat malaria)
- Anti-arrhythmic drugs (medications to treat arrhythmia)
CYP2B6 Inducers and Inhibitors
Inducers are substances that increase the metabolic activity of the enzyme. Inhibitors are substances that bind to the enzyme to reduce its activity.
Drugs that Induce CYP2B6 Activity
- Anticonvulsants/ anti-seizure drugs – These drugs are used in treating symptoms like seizures, epilepsy, insomnia, and even mood disorders. Drugs like phenobarbital and phenytoin induce CYP2B6 activity.
- Rifampin – Rifampin is an antibiotic and is used in treating bacterial infections. Rifampin induces CYP2B6 activity.
Inducers speed up the metabolism of the drugs, resulting in lower concentrations for drugs that are metabolized to an inactive form. In the case of antibiotics, inducers speed up the enzymatic conversion of antibiotics into their inactive forms, not giving the drug enough time to fight bacterial infections.
Drugs that Inhibit CYP2B6 Activity
- Antiretroviral drugs – Antiretroviral drugs are used to treat the Human Immunodeficiency Virus (HIV). Drugs like Ritonavir, efavirenz, and nelfinavir can inhibit CYP2B6 activity.
- Ticlopidine – Ticlopidine is an antiplatelet medicine and is used to prevent platelets from sticking together and forming clots. Ticlopidine inhibits CYP2B6 activity.
- Clopidogrel – Clopidogrel is also an antiplatelet medicine that inhibits CYP2B6 activity.
- Thiotepa – Thiotepa is a chemotherapy drug that inhibits CYP2B6 activity.
Variations in the CYP2B6 gene
More than 100 different variations (changes) have been identified in the CYP2B6 gene. These variations can increase or decrease the CYP2B6 enzyme levels in the body.
| Haplotype | Effects |
| CYP2B6*4 | Increased enzyme activity |
| CYP2B6*8 | Decreased enzyme activity |
| CYP2B6*11 | Decreased enzyme activity |
| CYP2B6*15 | Decreased enzyme activity |
| CYP2B6*18 | Decreased enzyme activity |
| CYP2B6*22 | Increased enzyme activity |
| CYP2B6*27 | Decreased enzyme activity |
A haplotype is a group of gene changes that are inherited together. The *4, *8, *11, *15, *18, *22, and *27 are all haplotypes. Star alleles are used to name different haplotypes.
CYP2B6*4 – The CYP2B6*4 is a haplotype of the CYP2B6 gene. The *4 allele of this gene results in increased enzymatic activity.
CYP2B6*18 – The *18 allele of this SNP is associated with lower CYP2B6 enzyme activity when compared to the normal allele. People with this allele have higher levels of drugs in the body and are at risk for overexposure to drugs like nevirapine and efavirenz.
CYP2B6*6 – People with the *6 allele have a higher risk of becoming smokers and have quicker relapses after quitting smoking.
Recommendations to Boost CYP2B6 Metabolism
Certain compounds reduce the enzymatic activity of CYP2B6. Depending on your genotype, you might want to include/avoid them in your diet.
- Berberine – Berberine is a type of alkaloid that is extracted from various plant sources. It is used in Traditional Chinese medicine practices to treat different health conditions. This alkaloid is known to decrease CYP2B6 activity.
- Allyl isothiocyanate – This is a colorless, pungent oil that gives a distinctive taste to radishes, mustard, and other strong-smelling vegetables. Studies show that this pungent oil decreases the activity of the CYP2B6 enzyme.
Genetic Testing
Genetic testing helps understand if you are at risk of high or low CYP2B6 enzyme activity. Smokers may benefit from this information as it can help them know their risk for overexposure to nicotine. People on certain medications may need to alter their dosages depending on the enzyme activity.
Summary
- The CYP2B6 gene helps produce the CYP2B6 enzyme. This enzyme is a part of the CYP superfamily and helps in clearing various toxins and drugs from the body.
- Recent studies show that about 4% of the top 200 prescription drugs sold in the United States are cleared by the CYP2B6 enzyme.
- The CYP2B6 enzyme clears nicotine, chemotherapeutics, antidepressants, anti-inflammatory drugs, psychotropic drugs, and certain hormones.
- Over 100 different variations in the CYP2B6 gene have been identified.
- Genetic testing helps understand if you are prone to higher or lower enzyme activity. It will also help customize drug levels for optimal efficiency.
- Dietary compounds containing substances like Berberine and Allyl isothiocyanate need to be consumed with caution.
References
https://europepmc.org/article/med/27865701
https://pubs.acs.org/doi/abs/10.1021/jf050064z
https://www.sciencedirect.com/science/article/pii/S2211383516302532
https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1555
https://www.sciencedirect.com/topics/neuroscience/cyp2b6
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CYP2B6
https://www.pharmgkb.org/vip/PA166169423
https://www.sciencedirect.com/science/article/pii/S0163725813000065
