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

Function

• NADPH-dependent electron transport pathway
• oxidizes a variety of structurally unrelated compounds
  • steroids, fatty acids, & xenobiotics
• see substrates the R form of warfarin is a substrate of cyt p450 1A2
• inducers
  • carbamazepine
  • lanzoprazole
  • omeprazole
  • phenobarbital
  • phenytoin
  • primidone
  • rifampin
  • ritonavir
  • St John's wort
  • 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
• 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%)
  • due to a substitution of a base in the non-coding region of the CYP1A2 gene
  • has the effect of decreasing the enzyme inducibility
  • individuals homozygous for the CYP1A2*1F allele are 'slow' caffeine metabolizers
  • 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

More general terms

• cytochrome P450 1A (CYP1A)

Database

• UniProt: http://www.uniprot.org/uniprot/P05177.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1544
• OMIM: https://mirror.omim.org/entry/108330
• OMIM: https://mirror.omim.org/entry/124060
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1544