cyp1a2 cyp1a2 cytochrome p450 1a2 (abbreviated cyp1a2), a member of the cytochrome p450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. in humans, the cyp1a2 enzyme is encoded by the cyp1a2 gene. cyp1a2available structurespdbortholog search: pdbe rcsb list of pdb id codes2hi4identifiersaliasescyp1a2, cp12, p3-450, p450(pa), cytochrome p450 family 1 subfamily a member 2, cytochrome p450 1a2, cypia2external idsomim: 124060 mgi: 88589 homologene: 68082 genecards: cyp1a2 gene location (human)chr.chromosome 15 (human)band15q24.1start74,748,845 bpend74,756,607 bpgene location (mouse)chr.chromosome 9 (mouse)band9 b|9 31.3 cmstart57,584,220 bpend57,590,986 bprna expression patternbgeehumanmouse (ortholog)top expressed inright lobe of liversuperficial temporal arterycardianipplevena cavasubthalamic nucleusspermventral tegmental areasuperior surface of tongueinferior ganglion of vagus nervetop expressed inleft lobe of liverolfactory epitheliumgallbladdersexually immature organismduodenumthoracic diaphragmright lung lobethymuspancreascolonmore reference expression databiogpsmore reference expression datagene ontologymolecular 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 transfer activity 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 metabolism epoxygenase p450 pathway cellular response to cadmium ion post-embryonic development monocarboxylic acid metabolic process response to organic substance oxidative demethylation 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 xenobiotic metabolic process porphyrin-containing compound metabolic process toxin biosynthetic process cellular response to copper ion electron transport chain long-chain fatty acid biosynthetic process sources:amigo / quickgoorthologsspecieshumanmouseentrez154413077ensemblensg00000140505ensmusg00000032310uniprotp05177p00186refseq (mrna)nm_000761nm_009993refseq (protein)np_000752np_034123location (ucsc)chr 15: 74.75 – 74.76 mbchr 9: 57.58 – 57.59 mbpubmed searchwikidataview/edit humanview/edit mouse 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 paracetamol (acetaminophen). the transcript from this gene contains four alu sequences flanked by direct repeats in the 3' untranslated region. cyp1a2 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-eicosatetraenoic acid and 17s,18r-eicosatetraenoic 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. the authoratitive list of star allele nomenclature for cyp1a2 along with activity scores is kept by pharmvar 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. cyp1a2 is also involved in the metabolization of caffeine, and the presence of alleles that make this metabolization slow have been associated with an increased risk of nonfatal myocardial infarction for those who drink a lot of coffee (4 per day and up). 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 of sensitive substrates metabolized through cyp1a2, or more than 80% decrease in clearance thereof. moderate inhibitor being one that causes at least a 2-fold increase in the plasma auc values of sensitive substrates metabolized through cyp1a2, or 50-80% decrease in clearance thereof. weak inhibitor being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma auc values of sensitive substrates metabolized through cyp1a2, or 20-50% decrease in clearance thereof. substratesinhibitorsinducers dietary flavonoids naringenin naringin quercetin rutin alosetron (5-ht3 antagonist) clopidogrel many antidepressants amitriptyline (tricyclic antidepressant) clomipramine (tricyclic antidepressant) imipramine (tricyclic antidepressant) agomelatine duloxetine (snri, sensitive substrates of cyp1a2) 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) ramelteon riluzole (in amyotrophic lateral sclerosis) tacrine (parasympathomimetic) tasimelteon tizanidine (α-2 adrenergic agonist) verapamil ( of calcium channel blocker, also classified as moderate sensitive substrate in cyp1a2) warfarin (anticoagulant) zileuton (in asthma) strong: many fluoroquinolones (broad-spectrum antibiotics), including: enoxacin ciprofloxacin fluvoxamine (ssri antidepressant) moderate st. john's wort methoxsalen (in psoriasis) mexiletine oral contraceptives weak acyclovir allopurinol mexiletine cimetidine (h2-receptor antagonist) caffeine echinacea peginterferon alpha-2a theophylline piperine verapamil (a non-dihydropyridine calcium channel blocker) according to uptodate. however, fass, a swedish national authority, attributes verapamil to strong cyp1a2 inhibitor. zileuton unspecified potency: interferon (antiviral, antiseptic, antioncogenic) mibefradil (calcium channel blocker) some foods grapefruit juice (its bitter flavanone naringenin) cumin turmeric isoniazid tetrahydropalmatine moderate inducers: tobacco phenytoin rifampin ritonavir teriflunomide unspecified potency: some foods/herbs: liquorice brassica broccoli brussels sprouts cauliflower chargrilled meat insulin (in diabetes) methylcholanthrene (carcinogen) modafinil (eugeroic) nafcillin (beta-lactam antibiotic) beta-naphthoflavone (chemopreventive) some proton pump inhibitors: omeprazole lansoprazole