cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)

Function: 1) NADPH-dependent electron transport pathway 2) oxidizes a variety of structurally unrelated compounds - steroids, fatty acids, & xenobiotics 3) see substrates the R form of warfarin is a substrate of cyt p450 1A2 4) inducers - carbamazepine - lanzoprazole - omeprazole - phenobarbital - phenytoin - primidone - rifampin - ritonavir - St John's wort - smoke - tipranavir 5) inhibitors - acyclovir - amiodarone - atazanavir - cimetidine - ciprofloxacin - citalopram - echinacea - enoxacin - ethinyl estradiol - famotidine - fluvoxamine - isoniazid - methoxsalen - mexiletine - norfloxacin - omeprazole - oral contraceptive - Piper methysticum (Kava-kava) - propafenone - tacrine - ticlopidine - verapamil - zafirlukast - zileuton 6) substrates - acetaminophen - amitriptyline - aprepitant - asenapine - bendamustine - caffeine - chlordiazepoxide - cinacalcet - clomipramine - clopidogrel - clozapine - cyclobenzaprine - desipramine - diazepam - duloxetine - erlotinib - estradiol - flutamide - fluvoxamine - haloperidol - imipramine - levobupivacaine - methadone - mexiletine - mirtazapine - naproxen - nortriptyline - olanzapine - ondansetron - propafenone - propranolol - ramelteon - rasagiline - riluzole - ropinirole - ropivacaine - tacrine - theophylline - tizanidine - verapamil - warfarin - zileuton - zolmitriptan Inhibition: - fluvoxamine is a strong inhibitor (see inhibitors) Structure: belongs to the cytochrome P450 family Compartment: endoplasmic reticulum membrane, peripheral membrane Alternative splicing: named isoforms=2 Expression: - liver - induced by nicotine, omeprazole, phenobarbital, primidone, rifampicin (see inducers) - induced by smoking & smoke in foods Polymorphism: - CYP1A2*1F allele common (40-50%) a) due to a substitution of a base in the non-coding region of the CYP1A2 gene b) has the effect of decreasing the enzyme inducibility c) individuals homozygous for the CYP1A2*1F allele are 'slow' caffeine metabolizers d) for these individuals, increased intake of caffeine seems to be associated with a concommitant increase in the risk of non-fatal myocardial infraction (MI) Laboratory: - CYP1A2 gene mutation

Related

CYP1A2 gene mutation cyt P450 1A2 gene

Properties

SIZE: entity length = 515 aa MW = 58 kD COMPARTMENT: endoplasmic reticulum MOTIF: Iron [Fe]-binding site SITE: 458-458 SUBSTRATE: acetaminophen amitriptyline aprepitant asenapine bendamustine caffeine chlordiazepoxide cinacalcet clomipramine clopidogrel clozapine cyclobenzaprine desipramine diazepam duloxetine erlotinib estradiol flutamide fluvoxamine haloperidol imipramine levobupivacaine methadone mexiletine mirtazapine naproxen nortriptyline olanzapine ondansetron propafenone propranolol ramelteon rasagiline riluzole ropinirole ropivacaine tacrine theophylline tizanidine verapamil warfarin zileuton zolmitriptan INDUCERS: carbamazepine lansoprazole omeprazole phenobarbital phenytoin primidone rifampin ritonavir Hypericum perforatum smoke tipranavir INHIBITORS: acyclovir amiodarone atazanavir cimetidine ciprofloxacin citalopram Echinacea enoxacin ethinyl estradiol famotidine fluvoxamine isoniazid methoxsalen mexiletine norfloxacin omeprazole oral contraceptive Piper methysticum (Kava-Kava) propafenone tacrine ticlopidine verapamil zafirlukast zileuton

Database Correlations

OMIM correlations UniProt P05177 Pfam PF00067 Entrez Gene 1544 Kegg hsa:1544 ENZYME 1.14.14.1