Cytochrome P450 2A6 (abbreviated CYP2A6) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. CYP2A6 is the primary enzyme responsible for the oxidation of nicotine and cotinine. It is also involved in the metabolism of several pharmaceuticals, carcinogens, and a number of coumarin-type alkaloids. CYP2A6 is the only enzyme in the human body that appreciably catalyzes the 7-hydroxylation of coumarin, such that the formation of the product of this reaction, 7-hydroxycoumarin, is used as a probe for CYP2A6 activity.
The CYP2A6 gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6.
Interactive pathway map
Distribution CYP2A6 localizes to the endoplasmic reticulum and is found predominantly in the liver.
Variability Significant interindividual variability in CYP2A6 apoprotein and mRNA levels has been observed.
Induction CYP2A6 is known to be inducible by phenobarbital and rifampicin, and it is suspected that other antiepileptic drugs may also have this effect.
CYP2A6 Ligands +Selected inducers, inhibitors and substrates of CYP2A6 Substrates Inhibitors Inducers Many Carcinogens MNAN NNK NDEA MTBE Other toxins aflatoxin B1 (mycotoxin) 1,3-butadiene (in synthetic rubber) coumarin (anticoagulant, found in cinnamon) DCBN (herbicide) 7-ethoxycoumarin (test substrate) skatole quinoline MOCA (in polyurethane production) halothane (anaesthetic) losigamone (anticonvulsant) methoxyflurane (anaesthetic) cotinine (metabolite of nicotine) nicotine (stimulant) SM-12502 (PAF antagonist) valproic acid (anticonvulsant, mood-stabilizing) dexmedetomidine (sedative) amiodarone (antiarrhythmic agent) amlodipine (calcium channel blocker) buprenorphine (semisynthetic opioid) clofibrate (fibrate) clotrimazole (antifungal) desipramine (tricyclic antidepressant) disulfiram (acetaldehyde dehydrogenase inhibitor) entacapone (COMT inhibitor, used in Parkinson's disease) fenofibrate (fibrate) gabapentin (anticonvulsant) grapefruit juice flavonoids isoniazid (antibacterial) ketoconazole (antifungal) letrozole (aromatase inhibitor, used in breast cancer) methimazole (antithyroid agent) methoxsalen (furanocoumarin, used in psoriasis) metyrapone (used to diagnose adrenal insufficiency) miconazole (antifungal) modafinil (wakefulness-promoting agent) nicotine (stimulant) orphenadrine (antihistamine) pilocarpine (muscarinic receptor agonist) pregabalin (anticonvulsant) selegiline (monoamine oxidase inhibitor) sulconazole (antifungal) tioconazole (antifungal) tranylcypromine (monoamine oxidase inhibitor) Barbiturates amobarbital pentobarbital phenobarbital secobarbital rifampicin (antibacterial)
See also List of cytochrome P450 modulators
References
Further reading
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