CYP1A2

Cytochrome P450, family 1, subfamily A, polypeptide 2
PDB rendering based on 2hi4.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2HI4
Identifiers
Symbols	CYP1A2 ; CP12; P3-450; P450(PA)
External IDs	OMIM: 124060 MGI: 88589 HomoloGene: 68082 ChEMBL: 3356 GeneCards: CYP1A2 Gene
EC number	1.14.14.1
Gene ontology Molecular function • monooxygenase activity • iron ion binding • electron carrier activity • oxidoreductase activity • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen • enzyme binding • heme binding • demethylase activity • caffeine oxidase activity • aromatase activity Cellular component • endoplasmic reticulum membrane • intracellular membrane-bounded organelle Biological process • steroid catabolic process • porphyrin-containing compound metabolic process • xenobiotic metabolic process • toxin biosynthetic process • post-embryonic development • alkaloid metabolic process • regulation of gene expression • monoterpenoid metabolic process • drug metabolic process • dibenzo-p-dioxin metabolic process • arachidonic acid metabolic process • epoxygenase P450 pathway • lung development • methylation • response to estradiol • response to lipopolysaccharide • monocarboxylic acid metabolic process • response to immobilization stress • drug catabolic process • exogenous drug catabolic process • small molecule metabolic process • cellular respiration • heterocycle metabolic process • hydrogen peroxide biosynthetic process • oxidation-reduction process • oxidative demethylation • cellular response to cadmium ion • oxidative deethylation • omega-hydroxylase P450 pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1544	13077
Ensembl	ENSG00000140505	ENSMUSG00000032310
UniProt	P05177	P00186
RefSeq (mRNA)	NM_000761	NM_009993
RefSeq (protein)	NP_000752	NP_034123
Location (UCSC)	Chr 15: 74.75 – 74.76 Mb	Chr 9: 57.68 – 57.68 Mb
PubMed search	[1]	[2]

Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.

Function

CYP1A2 is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. CYP1A2 localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), 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.

Effect of diet

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 activity of CYP1A2 in South Asians appears to be due to cooking these vegetables in curries using ingredients such as cumin and turmeric, ingredients known to inhibit the enzyme.

Ligands

Following is a table of selected substrates, inducers and inhibitors of CYP1A2.

Inhibitors of CYP1A2 can be classified by their potency, 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.
• 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 antidepressants amitriptyline (tricyclic antidepressant) clomipramine (tricyclic antidepressant) imipramine (tricyclic antidepressant) agomelatine some atypical antipsychotics clozapine olanzapine haloperidol (typical antipsychotic) caffeine (xanthine, stimulant) ropivacaine (local anaesthetic) theophylline (xanthine, in respiratory diseases) zolmitriptan (serotonin receptor agonist) melatonin (antioxidant, sleep-inducer) tamoxifen (SERM) erlotinib (Tarceva, a tyrosine kinase inhibitor) cyclobenzaprine (muscle relaxant, depressant) estradiol (in hypoestrogenism) fluvoxamine (SSRI antidepressant) mexiletine (antiarrhythmic agent) naproxen (NSAID) ondansetron (5-HT3 antagonist) phenacetin (analgesic) paracetamol (analgesic, antipyretic) propranolol (beta blocker) riluzole (in amyotrophic lateral sclerosis) tacrine (parasympathomimetic) tizanidine (α-2 adrenergic agonist) verapamil (calcium channel blocker) warfarin (anticoagulant) zileuton (in asthma)	Strong: ciprofloxacin (fluoroquinolone bactericidal) Many other fluoroquinolones (broad-spectrum antibiotics) fluvoxamine (SSRI antidepressant) verapamil (calcium channel blocker) Moderate St. John's wort Herbs and herbal Teas Peppermint, German Chamomile(Chamazulene), and Dandelion Teas Weak cimetidine (H2-receptor antagonist) caffeine Unspecified potency: amiodarone (antiarrhythmic agent) interferon (antiviral, antiseptic, antioncogenic) methoxsalen (in psoriasis) Mibefradil (calcium channel blocker) Some foods grapefruit juice (its bitter flavanone naringenin) cumin turmeric isoniazid	tobacco Some foods/herbs broccoli brussels sprouts Echinacea chargrilled meat cauliflower insulin (in diabetes) Methylcholanthrene (carcinogen) modafinil (eugeroic) nafcillin (beta-lactam antibiotic) beta-Naphthoflavone (chemopreventive) omeprazole (proton pump inhibitor)

See also

• Cytochrome P450 oxidase

This article incorporates text from the United States National Library of Medicine, which is in the public domain.