The Info List - CYP1A2

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ALIASES CYP1A2, CP12, P3-450, P450(PA), cytochrome P450 family 1 subfamily A member 2, Cytochrome P450
Cytochrome P450

EXTERNAL IDS OMIM: 124060 MGI: 88589 HomoloGene: 68082 GeneCards: CYP1A2


MOLECULAR FUNCTION • iron ion binding • demethylase 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 • metal ion binding • caffeine oxidase activity • heme binding • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen • enzyme binding • oxidoreductase activity • aromatase activity • electron carrier activity • oxygen binding • monooxygenase activity

CELLULAR COMPONENT • organelle membrane • endoplasmic reticulum membrane • intracellular membrane-bounded organelle • membrane • endoplasmic reticulum

BIOLOGICAL PROCESS • response to immobilization stress • toxin metabolic process • steroid metabolic process • response to estradiol • alkaloid metabolic process • response to organic cyclic compound • lung development • lipid metabolic process • exogenous drug catabolic process • epoxygenase P450 pathway • cellular response to cadmium ion • post-embryonic development • monocarboxylic acid metabolic process • response to organic substance • oxidative deethylation • oxidative demethylation • drug catabolic process • response to lipopolysaccharide • methylation • steroid catabolic process • omega-hydroxylase P450 pathway • dibenzo-p-dioxin metabolic process • heterocycle metabolic process • cellular respiration • cellular aromatic compound metabolic process • regulation of gene expression • hydrogen peroxide biosynthetic process • monoterpenoid metabolic process • drug metabolic process • xenobiotic metabolic process • oxidation-reduction process • response to drug • porphyrin-containing compound metabolic process • toxin biosynthetic process • cellular response to copper ion

Sources:Amigo / QuickGO


More reference expression data


















LOCATION (UCSC) Chr 15: 74.75 – 74.76 Mb Chr 9: 57.68 – 57.68 Mb



View/Edit Human View/Edit Mouse

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 .


* 1 Function * 2 Effect of diet * 3 Ligands * 4 See also * 5 References * 6 External links * 7 Further reading


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.

also metabolizes polyunsaturated fatty acids into signaling molecules that have physiological as well as pathological activities. It has monoxygenase activity for certain of these fatty acids in that it metabolizes arachidonic acid to 19-hydroxyeicosatetraenoic acid (19-HETE) (see 20-Hydroxyeicosatetraenoic acid ) but also has epoxygenase activity in that it metabolizes docosahexaenoic acid to epoxides , primarily 19R,20S-epoxyeicosapentaenoic acid and 19S,20R-epoxyeicosapentaenoic acid isomers (termed 19,20-EDP) and similarly metabolizes eicosapentaenoic acid to epoxides, primarily 17R,18S-eicosatetraenic acid and 17S,18R-eicosatetraenic acid isomers (termed 17,18-EEQ). 19-HETE is an inhibitor of 20-HETE, a broadly active signaling molecule, e.g. it constricts arterioles , elevates blood pressure, promotes inflammation responses, and stimulates the growth of various types of tumor cells; however the in vivo ability and significance of 19-HETE in inhibiting 20-HETE has not been demonstrated (see 20-Hydroxyeicosatetraenoic acid ). The EDP (see Epoxydocosapentaenoic acid ) and EEQ (see epoxyeicosatetraenoic acid ) metabolites have a broad range of activities. In various animal models and in vitro studies on animal and human tissues, they decrease hypertension and pain perception; suppress inflammation; inhibit angiogenesis , endothelial cell migration and endothelial cell proliferation; and inhibit the growth and metastasis of human breast and prostate cancer cell lines. It is suggested that the EDP and EEQ metabolites function in humans as they do in animal models and that, as products of the omega-3 fatty acids , docosahexaenoic acid and eicosapentaenoic acid, the EDP and EEQ metabolites contribute to many of the beneficial effects attributed to dietary omega-3 fatty acids. EDP and EEQ metabolites are short-lived, being inactivated within seconds or minutes of formation by epoxide hydrolases , particularly soluble epoxide hydrolase , and therefore act locally. CYP1A2
is not regarded as being a major contributor to forming the cited epoxides but could act locally in certain tissues to do so.


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.


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 of substrates. * MODERATE INHIBITOR being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance of substrates. * 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 of substrates.


* 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 )


* ciprofloxacin (fluoroquinolone bactericidal ) * Many other fluoroquinolones (broad-spectrum antibiotics ) * fluvoxamine ( SSRI antidepressant) * verapamil (calcium channel blocker )


* St. John\'s wort


* Peppermint, German Chamomile(Chamazulene), and Dandelion Teas


* cimetidine ( H2-receptor antagonist ) * caffeine * echinacea


* amiodarone (antiarrhythmic agent ) * interferon (antiviral , antiseptic , antioncogenic ) * methoxsalen (in psoriasis ) * Mibefradil (calcium channel blocker )


* grapefruit juice (its bitter flavanone naringenin ) * cumin * turmeric

* isoniazid

* tobacco


* broccoli * brussels sprouts * chargrilled meat * cauliflower

* insulin (in diabetes ) * methylcholanthrene (carcinogen ) * modafinil (eugeroic ) * nafcillin (beta-lactam antibiotic ) * beta-Naphthoflavone (chemopreventive ) * omeprazole (proton pump inhibitor )


* Cytochrome P450
Cytochrome P450


* ^ "Human PubMed
Reference:". * ^ "Mouse PubMed
Reference:". * ^ Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW (Jan 2004). "Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants". Pharmacogenetics. 14 (1): 1–18. PMID 15128046 . doi :10.1097/00008571-200401000-00001 . * ^ Jaiswal AK, Nebert DW, McBride OW, Gonzalez FJ (1987). "Human P(3)450: cDNA and complete protein sequence, repetitive Alu sequences in the 3' nontranslated region, and localization of gene to chromosome 15". Journal of Experimental Pathology. 3 (1): 1–17. PMID 3681487 . * ^ " Entrez
Gene: cytochrome P450". * ^ Westphal C, Konkel A, Schunck WH (Nov 2011). "CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?". Prostaglandins & Other Lipid Mediators. 96 (1-4): 99–108. PMID 21945326 . doi :10.1016/j.prostaglandins.2011.09.001 . * ^ A B Fleming I (Oct 2014). "The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease". Pharmacological Reviews. 66 (4): 1106–40. PMID 25244930 . doi :10.1124/pr.113.007781 . * ^ Zhang G, Kodani S, Hammock BD (Jan 2014). "Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer" . Progress in Lipid Research. 53: 108–23. PMC 3914417  . PMID 24345640 . doi :10.1016/j.plipres.2013.11.003 . * ^ He J, Wang C, Zhu Y, Ai D (Dec 2015). "Soluble epoxide hydrolase: A potential target for metabolic diseases". Journal of Diabetes. 8: 305–13. PMID 26621325 . doi :10.1111/1753-0407.12358 . * ^ A B Wagner K, Vito S, Inceoglu B, Hammock BD (Oct 2014). "The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling" . Prostaglandins & Other Lipid Mediators. 113-115: 2–12. PMC 4254344  . PMID 25240260 . doi :10.1016/j.prostaglandins.2014.09.001 . * ^ Fischer R, Konkel A, Mehling H, Blossey K, Gapelyuk A, Wessel N, von Schacky C, Dechend R, Muller DN, Rothe M, Luft FC, Weylandt K, Schunck WH (Mar 2014). "Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway" . Journal of Lipid Research. 55 (6): 1150–1164. PMC 4031946  . PMID 24634501 . doi :10.1194/jlr.M047357 . * ^ Prostaglandins Other Lipid Mediat. 2014 Oct;113-115:2-12. doi: 10.1016/j.prostaglandins.2014.09.001. Epub 2014 Sep 18. Review * ^ Fontana RJ, Lown KS, Paine MF, Fortlage L, Santella RM, Felton JS, Knize MG, Greenberg A, Watkins PB (Jul 1999). "Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers". Gastroenterology. 117 (1): 89–98. PMID 10381914 . doi :10.1016/S0016-5085(99)70554-8 . * ^ A B C D E Sanday, Kate (17 October 2011), "South Asians and Europeans react differently to common drugs", University of Sydney Faculty of Pharmacy News * ^ A B C Center for Drug Evaluation and Research. "Drug Interactions & Labeling - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers". www.fda.gov. Retrieved 2016-06-01. * ^ A B C D E F G H I J K L M N O P Q R S T U V W X Y Z AA AB AC AD AE AF AG AH AI AJ AK AL AM AN AO AP Flockhart DA (2007). "Drug Interactions: Cytochrome P450
Cytochrome P450
Drug Interaction Table". Indiana University School of Medicine . Retrieved on July 2011 * ^ A B C D E F G H I J K L M N O P Swedish environmental classification of pharmaceuticals - FASS (drug catalog) - Facts for prescribers (Fakta för förskrivare). Retrieved July 2011 * ^ "Erlotinib". Metabolized primarily by CYP3A4
and, to a lesser degree, by CYP1A2
and the extrahepatic isoform CYP1A1 * ^ Dostalek M, Pistovcakova J, Jurica J, Sulcová A, Tomandl J (Sep 2011). "The effect of St John's wort (hypericum perforatum) on cytochrome p450 1a2 activity in perfused rat liver". Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia. 155 (3): 253–7. PMID 22286810 . doi :10.5507/bp.2011.047 . * ^ Maliakal, Pius. "Effect of herbal teas on hepatic drug metabolizing enzymes in rats". Journal of Pharmacy and Pharmacology. Retrieved 29 December 2012. * ^ "Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers". U.S. Food and Drug Administration. * ^ Gorski JC, Huang SM, Pinto A, Hamman MA, Hilligoss JK, Zaheer NA, Desai M, Miller M, Hall SD (Jan 2004). "The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo". Clinical Pharmacology and Therapeutics. 75 (1): 89–100. PMID 14749695 . doi :10.1016/j.clpt.2003.09.013 . * ^ Fuhr U, Klittich K, Staib AH (Apr 1993). "Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man" . British Journal of Clinical Pharmacology. 35 (4): 431–6. PMC 1381556  . PMID 8485024 . doi :10.1016/0024-3205(96)00417-1