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Cytochrome P450 1A2
2HI4

Synonyms

CYP1A2

PDB

Search for UniProt ID P05177.

Example IDs
2HI4

Proteopedia

N/A

Jmol applet of 2HI4

2HI4.

No. of amino acids

514

FASTA

Sequence
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKNPHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDGQSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELMAGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFPILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGNLIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLSDRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPELWEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLEFSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN

MeSH

D019388
Review search.

UniProt

P05177

Entrez

1544

Cytochrome P450 1A2 (or CYP1A2 for short) is an enzyme found in the liver that metabolizes (chemically changes them so as to make then easier to excrete in urine and faeces) drugs, toxins and hormones. Substrates, in this context, are agents that are metabolized by CYP1A2; inhibitors inhibit the enzyme, hence reducing its ability to metabolize drugs, food components and hormones, this usually means that they amplify exposure to these agents; inducers induce the enzyme, hence increasing its ability to perform its various functions such as metabolizing drugs, food components, toxins and hormones and reducing exposure to these agents.[1] Changing exposure means changing the frequency and/or severity of side effects and changing the drug's ability to do what it is desired to do. Usually this necessitates a dose adjustment, although in cases where the difference between a safe, therapeutic dose and a toxic dose is very little (like with paracetamol) sometimes the drug may be avoided altogether, or if the change in exposure is minor or such that the exposure is lessened no dose adjustment may be required. 

Note: below drugs are called by their generic name, their brand names can usually be found by searching this website.

SubstratesEdit

Note: the percentage of the drug that is metabolized via this enzyme is listed in brackets. Bolded are agents that are not marketed in Australia; italicized (which is the format of this note: slanted) are agents not marketed in the USA.; underlined are agents that are not marketed in the UK; * indicates agents that were once marketed in at least one of these three countries but is no longer. In the notes drug names are bolded to make them easier to find.

Sources[2][3]

  • Anti-arrhythmic agents[note 1] specifically amiodarone (5-10%), disopyramide (5-10%), mexiletine* (10-20%) and propafenone (10-25%).
  • Anti-cancer agents specifically axitinib, bortezomib (10-25%), dacarbazine (20-40%), erlotinib (5-10%), flutamide (10-25%), imatinib (5-10%), tegafur (10-20%) and thalidomide (5-10%).
  • Antidepressants namely agomelatine, amitriptyline (5-10%), clomipramine (5-10%), desipramine (5-15%), doxepin (5-10%), duloxetine (30-40%), fluoxetine (5-15%), fluvoxamine (5-10%), imipramine (10-20%), maprotiline (5-10%), mianserin (5-10%), mirtazapine (5-15%), sertraline (5-10%) and trazodone (15-20%).
  • Antihistamines[note 2] like azelastine (5-10%), cinnarizine (5-10%), diphenhydramine (5-10%) and flunarizine (5-10%),
  • Anti-hypertensive agents[note 3] namely bufuralol (5-10%), carvedilol (5-10%) and propanolol (30-50%).
  • Anti-infective agents like albendazole (5-10%), pefloxacin (5-10%), primaquine (10-20%), proguanil, resiquimod (5-10%), terbinafine (10-25%) and tiabendazole* (10-20%).
  • Anti-Parkinson's drugs like rasagiline, ropinirole (30-40%) and selegiline (5-15%).
  • Antipsychotics namely asenapine, clozapine (40-55%), haloperidol (5-10%), iloperidone (5-10%), olanzapine (30-40%), perphenazine (5-10%), pimozide (10-20%), promazine (30-45%), thioridazine (35-45%) and zotepine* (5-10%).
  • Digestive drugs[note 4] namely alosetron (10-20%), cisapride* (5-15%), metoclopramide (5-10%) and ondansetron (5-10%).
  • Local anaesthetics namely bupivacaine (5-10%), lidocaine (10-20%) and ropivacaine (50-65%).
  • Miscellaneous others[note 5] including caffeine (>95%), carbamazepine (5-10%),[note 6] chlorzoxazone* (5-10%), furafylline (10-20%), leflunomide (40-55%), lisofylline (5-10%), melatonin (40-60%), paraxanthine (80%), pentoxifylline (or oxpentifylline in Australia; 10-20%), pioglitazone (15-30%), ranitidine (5-15%), riluzole (75-80%), tacrine* (50-65%), theophylline (90-95%), tizanidine (80-95%), verapamil, warfarin (R-enantiomer [mirror form of the molecule]; 10-20%), zileuton (5-15%), zolmitriptan (30-40%) and zoxazolamine (5-10%).
  • Painkillers including metamizole* (10-25%), nabumetone (30%), naproxen (5-10%), paracetamol (acetaminophen; 10-15%) and rofecoxib* (5-10%).
  • Sedatives including flunitrazepam (5-10%), indiplon (5-10%), propofol (10-25%) and zolpidem (5-10%).

InhibitorsEdit

Inhibitors include (same font rules apply as before, unless they were listed as substrates):[2][3]

  • Carbamazepine
  • Cimetidine[note 7]
  • Ciprofloxacin (strong)[note 8]
  • Certain carcinogens (cancer-causing substances)
  • Dihydralazine[note 9]
  • Duloxetine
  • Furafylline
  • Fluvoxamine (strong)
  • Isoniazid[note 10]
  • Organophosphate pesticides
  • Resveratrol[note 11]
  • Rofecoxib
  • Tiabendazole
  • Vemurafenib[note 12]
  • Verapamil
  • Zileuton

InducersEdit

They include:[2][3]

  • Anti-malaria agents such as primaquine and quinine
  • Caffeine
  • Carbamazepine[note 13]
  • Cruciferous vegetables like bok choy, broccoli, cabbage, cauliflower, etc.
  • Proton-pump inhibitors[note 14] such as lansoprazole, omeprazole and pantoprazole
  • Ritonivir (an anti-HIV medicine)
  • Tobacco smoke

External linksEdit

NotesEdit

  1. These are agents that affect the beating of the heart, usually used to correct dangerously irregular heart rhythms
  2. These are agents used for their sedating, anti-nausea/vomiting (usually in pregnancy) and anti-allergy effects; diphenhydramine is, under the brand name Benadryl, popularly used as a sleeping aid
  3. Blood pressure-lowering medicines
  4. Alosetron is used to treat irritable bowel syndrome, cisapride is used to treat chronic constipation, metoclopramide and ondansetron are used to treat nausea and/or vomiting. Metoclopramide may also be used to treat migraine (in combination with paracetamol) and gastric stasis, which is when the stomach is not emptying into the small intestine as quickly as it should or not at all.
  5. Chlorzoxazone is used to relax muscles, as is tizanidine and zoxazolamine; zolmitriptan is used to relieve migraines during an attack; warfarin is used to prevent blood clots; pioglitazone is used to treat type II diabetes mellitus; riluzole is used to treat amyotropic lateral sclerosis which is the disease that afflicts Stephen Hawking; tacrine is used to treat Alzheimer's disease; furafylline, theophylline and zileuton are used to treat asthma; ranitidine is used to treat stomach ulcers, acid reflux disease and indigestion/heartburn; melatonin is a sleep hormone that is used to help people fall and stay asleep; leflunomide is used to treat rheumatoid arthritis and other inflammatory conditions; paraxanthine is the major compound the body metabolizes caffeine into; pentoxifylline is used to treat peripheral vascular disease; lisofylline is used to treat inflammatory conditions; verapamil is used to treat heart failure.
  6. Used to treat epilepsy, bipolar disorder and a pain condition called trigeminal neuralgia
  7. Used to treat stomach ulcers, indigestion/heartburn, acid reflux disease and scleroderma (a condition in which the immune system, which normally defends the body from invaders, attacks healthy tissue-related oesophageal complications.
  8. An antibiotic
  9. Used to treat heart failure
  10. Used to treat tuberculosis
  11. Found in various natural sources, most notably grapes, grape juice and wine.
  12. Used to treat melanoma, the most deadly form of skin cancer
  13. Carbamazepine's actions on CYP1A2 is complex; it can inhibit or induce this enzyme
  14. Agents that reduce stomach acid production via interacting with the "pump" that forces acidic protons into the stomach

Reference listEdit

  1. Brunton, LL; Chabner, BA; Knollmann, BC, ed. (2010). Goodman & Gilman's Pharmacological Basis of Therapeutics. (12th ed.). New York, USA: McGraw-Hill Professional. ISBN 9780071624428. 
  2. 2.0 2.1 2.2 Rossi, S, ed. (July 2014). "Drugs and CYP enzymes". Australian Medicines Handbook. Adelaide, Australia: Australian Medicines Handbook Pty Ltd. Retrieved 16 August 2014. 
  3. 3.0 3.1 3.2 Zhou, SF; Wang, B; Yang, LP; Liu, JP (May 2010). "Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2.". Drug Metabolism Reviews 42 (2): 268–354. PMID 19961320. doi:10.3109/03602530903286476. 

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