Cytochrome P450 1A2 a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotic

Xenobiotic

A xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it. It can also cover substances which are present in much higher concentrations than are usual...

s in the body. In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

Expression of CYP1A2 appears to be induced by various dietary constituents.Vegetables such as cabbages, cauliflower and broccoli are known to increase levels of CYP1A2,lower levels of CYP1A2 in South Asians appears to be due to cooking these vegetables in curries using ingredients such as cumin

Cumin

Cumin is a flowering plant in the family Apiaceae, native from the east Mediterranean to India. Its seeds are used in the cuisines of many different cultures, in both whole and ground form.-Etymology:...

 and tumeric, ingredients known to inhibit the enzyme.

Function

CYP1A2 is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenase

Monooxygenase

Monooxygenases are enzymes that incorporate one hydroxyl group into substrates in many metabolic pathways. In this reaction, two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation of NADH.-Classification:...

s which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. CYP1A2 localizes to the endoplasmic reticulum

Endoplasmic reticulum

The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 and its expression is induced by some polycyclic aromatic hydrocarbons (PAH

Polycyclic aromatic hydrocarbon

Polycyclic aromatic hydrocarbons , also known as poly-aromatic hydrocarbons or polynuclear aromatic hydrocarbons, are potent atmospheric pollutants that consist of fused aromatic rings and do not contain heteroatoms or carry substituents. Naphthalene is the simplest example of a PAH...

s), some of which are found in cigarette smoke. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region.

Ligands

Following is a table of selected substrates, inducers

Enzyme induction and inhibition

Enzyme induction is a process in which a molecule induces the expression of an enzyme.Enzyme inhibition can refer to* the inhibition of the expression of the enzyme by another molecule...

 and inhibitors

Enzyme induction and inhibition

Enzyme induction is a process in which a molecule induces the expression of an enzyme.Enzyme inhibition can refer to* the inhibition of the expression of the enzyme by another molecule...

 of CYP1A2.

Inhibitors of CYP1A2 can be classified by their potency

Potency (pharmacology)

In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...

, such as:

• Strong inhibitor being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance
  Clearance (medicine)
  In medicine, the clearance is a measurement of the renal excretion ability. Although clearance may also involve other organs than the kidney, it is almost synonymous with renal clearance or renal plasma clearance. Each substance has a specific clearance that depends on its filtration characteristics...
  
  .
• Moderate inhibitor being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.
• Weak inhibitor being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.

Substrates	Inhibitors	Inducers
many antidepressant Antidepressant An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;... s amitriptyline Amitriptyline Amitriptyline is a tricyclic antidepressant . It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs...  (tricyclic antidepressant Tricyclic antidepressant Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms... ) clomipramine Clomipramine Clomipramine is a tricyclic antidepressant . It was developed in the 1960s by the Swiss drug manufacturer Geigy and has been in clinical use worldwide ever since.- Indications :...  (tricyclic antidepressant) imipramine Imipramine Imipramine , also known as melipramine, is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group...  (tricyclic antidepressant) agomelatine some atypical antipsychotic Atypical antipsychotic The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia... s clozapine Clozapine Clozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew... olanzapine Olanzapine Olanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder... haloperidol Haloperidol Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....  (typical antipsychotic Typical antipsychotic Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis... ) caffeine Caffeine Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...  (stimulant Stimulant Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others... ) ropivacaine Ropivacaine Ropivacaine is a local anaesthetic drug belonging to the amino amide group. The name ropivacaine refers to both the racemate and the marketed S-enantiomer...  (local anaesthetic) theophylline Theophylline Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...  (xanthine Xanthine Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine.... , in respiratory disease Respiratory disease Respiratory disease is a medical term that encompasses pathological conditions affecting the organs and tissues that make gas exchange possible in higher organisms, and includes conditions of the upper respiratory tract, trachea, bronchi, bronchioles, alveoli, pleura and pleural cavity, and the... s) zolmitriptan Zolmitriptan Zolmitriptan is a selective serotonin receptor agonist of the 1B and 1D subtypes. It is a triptan, used in the acute treatment of migraine attacks with or without aura and cluster headaches....  (serotonin receptor agonist Serotonin receptor agonist A serotonin receptor agonist is a compound that activates serotonin receptors, mimicking the effect of the neurotransmitter serotonin. There are various serotonin receptors and ligands.-5-HT1A receptor:... ) melatonin Melatonin Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...  (antioxidant, sleep-inducer) tamoxifen Tamoxifen Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...  (SERM Selective estrogen receptor modulator Selective Estrogen Receptor Modulators are a class of compounds that act on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively... ) erlotinib Erlotinib Erlotinib hydrochloride is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor . It is marketed in the United States by Genentech and OSI...  (Tarceva, a tyrosine kinase inhibitor) cyclobenzaprine Cyclobenzaprine Cyclobenzaprine is a muscle relaxant medication used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions. It is the most well-studied drug for this application, and it also has been used off-label for fibromyalgia treatment.- Mechanism of action :The mechanism...  (muscle relaxant Muscle relaxant A muscle relaxant is a drug which affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics... , depressant Depressant A depressant, or central depressant, is a drug or endogenous compound that depresses the function or activity of a specific part of the brain... ) estradiol Estradiol Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...  (in hypoestrogenism Hypoestrogenism Hypoestrogenism refers to a lower than normal level of estrogen, the primary sex hormone for women. In general, lower levels of estrogen may cause differences in the breasts, genitals, urinary tract and skin.... ) fluvoxamine Fluvoxamine Fluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder...  (SSRI antidepressant) mexiletine Mexiletine Mexiletine belongs to the Class IB anti-arrhythmic group of medicines. It is used to treat arrhythmias within the heart, or seriously irregular heartbeats. It slows conduction in the heart and makes the heart tissue less sensitive. Dizziness, heartburn, nausea, nervousness, trembling, unsteadiness...  (antiarrhythmic agent Antiarrhythmic agent Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress abnormal rhythms of the heart , such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation.... ) naproxen Naproxen Naproxen sodium is a nonsteroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as:...  (NSAID) ondansetron Ondansetron Ondansetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic , often following chemotherapy. Its effects are thought to be on both peripheral and central nerves...  (5-HT3 antagonist 5-HT3 antagonist The 5-HT3 antagonists are a class of medications that act as receptor antagonists at the 5-HT3 receptor, a subtype of serotonin receptor found in terminals of the vagus nerve and in certain areas of the brain.... ) phenacetin Phenacetin Phenacetin is an analgesic, once widely used; its use has declined because of its adverse effects.-History:Phenacetin was introduced in 1887, and was used principally as an analgesic, and was one of the first synthetic fever reducers to go on the market...  (analgesic Analgesic An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos .... ) paracetamol Paracetamol Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...  (analgesic Analgesic An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos .... , antipyretic Antipyretic Antipyretics ; an-tee-pahy-ret-iks; from the Greek anti, against, and pyreticus, are drugs or herbs that reduce fever. Normally, they will not lower body temperature if one does not have a fever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature... ) propranolol  (beta blocker Beta blocker Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,... ) riluzole Riluzole Riluzole is a drug used to treat amyotrophic lateral sclerosis. It delays the onset of ventilator-dependence or tracheostomy in selected patients and may increase survival by approximately 3–5 months....  (in amyotrophic lateral sclerosis Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input... ) tacrine Tacrine Tacrine is a centrally acting anticholinesterase and indirect cholinergic agonist . It was the first centrally-acting cholinesterase inhibitor approved for the treatment of Alzheimer's disease, and was marketed under the trade name Cognex. Tacrine was first synthesised by Adrien Albert at the...  (parasympathomimetic) tizanidine Tizanidine Tizanidine is a drug that is used as a muscle relaxant. It is a centrally acting α2 adrenergic agonist. It is used to treat the spasms, cramping, and tightness of muscles caused by medical problems such as multiple sclerosis, spastic diplegia, back pain, or certain other injuries to the spine or...  (α-2 adrenergic agonist) verapamil Verapamil Verapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...  (calcium channel blocker Calcium channel blocker A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with... ) warfarin Warfarin Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...  (anticoagulant Anticoagulant An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis... ) zileuton Zileuton Zileuton is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes formation. Zileuton is used for the maintenance treatment of asthma. Zileuton was introduced in 1996 by Abbott Laboratories and is now marketed in two formulations by Cornerstone Therapeutics Inc. under the...  (in asthma Asthma Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath... )	Strong: ciprofloxacin Ciprofloxacin Ciprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...  (fluoroquinolone bactericidal) Many other fluoroquinolones (broad-spectrum antibiotics) fluvoxamine Fluvoxamine Fluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder...  (SSRI antidepressant) verapamil Verapamil Verapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...  (calcium channel blocker Calcium channel blocker A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with... ) Weak cimetidine Cimetidine Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...  (H2-receptor antagonist H2-receptor antagonist The H2 receptor antagonists are a class of drugs used to block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells. H2 antagonists are used in the treatment of dyspepsia, although they have been surpassed in popularity by the more effective ... ) Unspecified potency: grapefruit juice Grapefruit juice Grapefruit juice is the fruit juice from grapefruits. It is rich in Vitamin C and ranges from sweet-tart to very sour. It is considered by some cultures to be a mystical tonic which promotes health and vigor. Certain civilizations have had holy men who live on Grapefruit juice alone...  (its bitter flavanone naringenin Naringenin Naringenin is a flavanone, a type of flavonoid, that is considered to have a bioactive effect on human health as antioxidant, free radical scavenger, anti-inflammatory, carbohydrate metabolism promoter, and immune system modulator. It is the predominant flavanone in grapefruit.-Biological... ) amiodarone Amiodarone Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...  (antiarrhythmic agent Antiarrhythmic agent Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress abnormal rhythms of the heart , such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation.... ) interferon Interferon Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...  (antiviral Antiviral drug Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses... , antiseptic Antiseptic Antiseptics are antimicrobial substances that are applied to living tissue/skin to reduce the possibility of infection, sepsis, or putrefaction... , antioncogenic) methoxsalen Methoxsalen Methoxsalen is a drug used to treat psoriasis, eczema, vitiligo, and some cutaneous Lymphomas in conjunction with exposing the skin to sunlight. Methoxsalen is extracted from Ammi majus, a plant of the family Apiaceae...  (in psoriasis Psoriasis Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of... ) Mibefradil Mibefradil Mibefradil is a drug for the treatment of hypertension and chronic angina pectoris. It belongs to a group known as calcium channel blockers.It is nonselective....  (calcium channel blocker Calcium channel blocker A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with... )	tobacco Tobacco Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines... Some foods broccoli Broccoli Broccoli is a plant in the cabbage family, whose large flower head is used as a vegetable.-General:The word broccoli, from the Italian plural of , refers to "the flowering top of a cabbage".... brussels sprout Brussels sprout The Brussels sprout is a cultivar of wild cabbage grown for its edible buds. The leafy green vegetables are typically 2.5–4 cm in diameter and look like miniature cabbages. The sprout is Brassica oleracea, in the "gemmifera" group of the family Brassicaceae... s chargrill Grilling Grilling is a form of cooking that involves dry heat applied to the surface of food, commonly from above or below.Grilling usually involves a significant amount of direct, radiant heat, and tends to be used for cooking meat quickly and meat that has already been cut into slices... ed meat Meat Meat is animal flesh that is used as food. Most often, this means the skeletal muscle and associated fat and other tissues, but it may also describe other edible tissues such as organs and offal... insulin Insulin Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....  (in diabetes) Methylcholanthrene Methylcholanthrene Methylcholanthrene is a highly carcinogenic polycyclic aromatic hydrocarbon produced by burning organic compounds at very high temperatures. It is a yellow solid with a melting point around 180 °C. Methylcholanthrene is used in laboratory studies of chemical carcinogenesis. It is an...  (carcinogen Carcinogen A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes... ) modafinil Modafinil Modafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...  (eugeroic Eugeroic Eugeroics are a chemical class of psychoactive drugs which act as stimulants, and are also known as wakefulness-promoting agents. They are used mainly in the treatment of sleeping disorders, excessive daytime sleepiness and narcolepsy, though they are also used merely to counteract fatigue and... ) nafcillin (beta-lactam antibiotic Beta-lactam antibiotic β-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-lactam nucleus in its molecular structure. This includes penicillin derivatives , cephalosporins , monobactams, and carbapenems... ) beta-Naphthoflavone Beta-Naphthoflavone beta-Naphthoflavone, also known as 5,6-benzoflavone, is a potent agonist of the aryl hydrocarbon receptor and as such is an inducer of such detoxification enzymes as cytochromes P450 and uridine 5'-diphospho-glucuronosyltransferases . β-Naphthoflavone is a putative chemopreventive agent....  (chemopreventive) omeprazole Omeprazole Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome...  (proton pump inhibitor Proton pump inhibitor Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar... )

See also

• Cytochrome P450 oxidase
  Cytochrome P450 oxidase
  The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...