関: CYP1A1

WordNet

the 16th letter of the Roman alphabet (同)p
(biochemistry) a class of hemoprotein whose principal biological function is electron transfer (especially in cellular respiration)
a river in western Thailand; a major tributary of the Chao Phraya (同)Ping River

PrepTutorEJDIC

parking
phosphorusの化学記号
palladiumの化学記号

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/17 17:14:12」(JST)

wiki en

Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein^[1] that in humans is encoded by the CYP1A1 gene.^[2] The protein is a member of the cytochrome P450 superfamily of enzymes.^[3]

Function

CYP1A1 is involved in phase I xenobiotic and drug metabolism (one substrate of it is theophylline). It is inhibited by fluoroquinolones and macrolides and induced by aromatic hydrocarbons.^[4]

CYP1A1 is also known as AHH (aryl hydrocarbon hydroxylase). It is involved in the metabolic activation of aromatic hydrocarbons (polycyclic aromatic hydrocarbons, PAH), for example, benzo(a)pyrene (BP), by transforming it to an epoxide. In this reaction, the oxidation of benzo[a]pyrene is catalysed by CYP1A1 to form BP-7,8-epoxide, which can be further oxidized by epoxide hydrolase (EH) to form BP-7,8-dihydrodiol. Finally CYP1A1 catalyses this intermediate to form BP-7,8-dihydrodiol-9,10-epoxide, which is the ultimate carcinogen.^[5]

However, an in vivo experiment with gene-deficient mice has found that the hydroxylation of benzo(a)pyrene by CYP1A1 can have an overall protective effect on the DNA, rather than contributing to potentially carcinogenic DNA modifications. This effect is likely due to the fact that CYP1A1 is highly active in the intestinal mucosa, and thus inhibits infiltration of ingested benzo(a)pyrene carcinogen into the systemic circulation.^[6]

Regulation

The expression of the CYP1A1 gene, along with that of CYP1A2/1B1 genes, is regulated by a heterodimeric transcription factor that consist of the aryl hydrocarbon receptor, a ligand activated transcription factor, and the aryl hydrocarbon receptor nuclear translocator.^[7] In the intestine, but not the liver, CYP1A1 expression moreover depends on TOLL-like receptor 2 (TLR2),^[8] which recognizes bacterial surface structures such as lipoteichoic acid.

Polymorphisms

Several polymorphisms have been identified in CYP1A1, some of which lead to more highly inducible AHH activity. CYP1A1 polymorphisms include:^[9]^[10]^[11]^[12]

M1, T→C substitution at nucleotide 3801 in the 3'-non-coding region
M2, A→G substitution at nucleotide 2455 leading to an amino acid change of isoleucine to valine at codon 462
M3, T→C substitution at nucleotide 3205 in the 3'-non-coding region
M4, C→A substitution at nucleotide 2453 leading to an amino acid change of threonine to asparagine at codon 461

The highly inducible forms of CYP1A1 are associated with an increased risk of lung cancer in smokers. (Reference = Kellerman et al., New Eng J Med 1973:289;934-937) Light smokers with the susceptible genotype CYP1A1 have a sevenfold higher risk of developing lung cancer compared to light smokers with the normal genotype.

References

^ Kawajiri K (1999). "CYP1A1". IARC Scientific Publications (148): 159–72. PMID 10493257.
^ Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW (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. doi:10.1097/00008571-200401000-00001. PMID 15128046.
^ Smith G, Stubbins MJ, Harries LW, Wolf CR (1998). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157.
^ Beresford AP (1993). "CYP1A1: friend or foe?". Drug Metabolism Reviews 25 (4): 503–17. doi:10.3109/03602539308993984. PMID 8313840.
^ Beresford, AP (1993). "CYP1A1: friend or foe?". Drug Metab Rev 25 (4): 503–17. doi:10.3109/03602539308993984. PMID 8313840.
^ Uno, S (2004). "Oral exposure to benzo[a]pyrene in the mouse: detoxication by inducible cytochrome P450 is more important than metabolic activation.". Mol Pharmacol 65 (5): 1225–37. doi:10.1124/mol.65.5.1225. PMID 15102951.
^ Ma Q, Lu AY (2007). "CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies". Drug Metabolism and Disposition 35 (7): 1009–16. doi:10.1124/dmd.107.015826. PMID 17431034.
^ Do, KN; Fink, LN; Jensen, TE; Gautier, L; Parlesak, A (2012). "TLR2 controls intestinal carcinogen detoxication by CYP1A1.". PLoS ONE 7 (3): e32309. doi:10.1371/journal.pone.0032309. PMC 3307708. PMID 22442665.
^ Petersen DD, McKinney CE, Ikeya K, Smith HH, Bale AE, McBride OW, Nebert DW (1991). "Human CYP1A1 gene: cosegregation of the enzyme inducibility phenotype and an RFLP". American Journal of Human Genetics 48 (4): 720–5. PMC 1682951. PMID 1707592.
^ Cosma G, Crofts F, Taioli E, Toniolo P, Garte S (1993). "Relationship between genotype and function of the human CYP1A1 gene". Journal of Toxicology and Environmental Health 40 (2-3): 309–16. doi:10.1080/15287399309531796. PMID 7901425.
^ Crofts F, Taioli E, Trachman J, Cosma GN, Currie D, Toniolo P, Garte SJ (1994). "Functional significance of different human CYP1A1 genotypes". Carcinogenesis 15 (12): 2961–3. doi:10.1093/carcin/15.12.2961. PMID 8001264.
^ Kiyohara C, Hirohata T, Inutsuka S (1996). "The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene". Japanese Journal of Cancer Research 87 (1): 18–24. doi:10.1111/j.1349-7006.1996.tb00194.x. PMID 8609043.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. Pharmacology of antimicrobial agents for treatment of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus
2. 薬と肝臓：代謝および肝障害の機序 drugs and the liver metabolism and mechanisms of injury
3. 薬理ゲノム学の概要 overview of pharmacogenomics
4. アゾールの薬理学 pharmacology of azoles
5. 第1世代抗精神病剤：薬理学、投与、および副作用の比較 first generation antipsychotic medications pharmacology administration and comparative side effects

English Journal

Trans-Resveratrol Enhances the Anticoagulant Activity of Warfarin in a Mouse Model.

Chiba T1, Kimura Y, Suzuki S, Tatefuji T, Umegaki K.
Journal of atherosclerosis and thrombosis.J Atheroscler Thromb.2016 Mar 5. [Epub ahead of print]
AIM: Resveratrol is a popular ingredient in dietary supplements. Some patients concomitantly use dietary supplements and medicines in Japan. In the present study, we determined whether trans-resveratrol and melinjo (Gnetum gnemon L.) seed extract (MSE), which contains resveratrol dimers, interacted
PMID 26947597

Andrographolide Ameliorates Beta-Naphthoflavone-Induced CYP1A Enzyme Activity and Lipid Peroxidation in Hamsters with Acute Opisthorchiasis.

Udomsuk L, Chatuphonprasert W, Jarukamjorn K, Sithithaworn P.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet.J Med Assoc Thai.2016 Jan;99 Suppl 1:S22-7.
BACKGROUND: Opisthorchis viverrini (OV) infection generates oxidative stress/free radicals and is considered as a primary cause ofcholangiocarcinoma since it primarily triggers sclerosing cholangitis.OBJECTIVE: In this study, the impacts of andrographolide on acute opisthorchaisis in β-naphthoflavo
PMID 26817235

Analysis of CYP1A1 and COMT polymorphisms in women with cervical cancer.

Kleine JP1, Camargo-Kosugi CM1,2, Carvalho CV1, Silva FC3,4, Silva ID1,5.
Genetics and molecular research : GMR.Genet Mol Res.2015 Dec 29;14(4):18965-73. doi: 10.4238/2015.December.29.3.
The aim of this case-control study was to obtain a comprehensive panel of genetic polymorphisms present only in genes (cytochrome P-450 1A1 - CYP1A1 and catechol-O-methyl transferase - COMT) within the metabolic pathway of sex steroids and determine their possible associations with the presence or a
PMID 26782546

Japanese Journal

イソチオシアネートとクルクミンによるラットにおける乳腺と食道抗発がん作用と代謝活性化(第15回公開シンポジウム「食べ物によるがん予防戦略を考える : 生活環境中の植物成分の抗変異・抗発がん作用とそのメカニズム」)

森幸雄,立松憲次郎,小出彰宏 [他],杉江茂幸,田中卓二,森秀樹
環境変異原研究 26(3), 221-231, 2004-12-20
… Hepatic cytochrome P-450(CYP)1A1, 51 and 53kDa proteins and constitutive CYP1A2 (3.8-fold) and 2B2 (4.0-fold), but not CYP2B1, 2E1 and 3A2, were induced by i.g. … Feeding 400 p.p.m. α-naphthyl isothiocyanate (ANIT) in a high fat diet for 3 weeks induced three CYP1A proteins but not CYP1A2; …
NAID 110001713957

Lack of an Inducible Effect of Dietary Soy Isoflavones on the mRNA Abundance of Hepatic Cytochrome P-450 Isozymes in Rats

Kishida Taro,Nagamoto Manabu,Ohtsu Yohhei [他],WATAKABE Miho,OHSHIMA Daisuke,NASHIKI Kunitaka,MIZUSHIGE Takafumi,IZUMI Tohru,OBATA Akio,EBIHARA Kiyoshi
Bioscience, biotechnology, and biochemistry 68(3), 508-515, 2004-03-23
… Modulation of the activity and content of cytochrome P-450 (CYP) in hepatic microsomes may be important to human health since these enzymes activate and inactivate a wide range of xenobiotics and food components. …
NAID 10013142524

The Effect of Dietary Fatty Acids on the Expression Levels and Activities of Hepatic Drug Metabolizing Enzymes

Kato Junko,Ikemoto Atsushi,Mizutani Takaharu
Journal of health science 49(2), 105-114, 2003-04-01
… The levels of CYP1A1, 1A2 and 2E1 were similar between the two oil groups. …
NAID 110003609050

Related Pictures

★リンクテーブル★

リンク元	「チトクロムP450酵素CYP1A1」
関連記事	「P」「CYP1A1」「p」「Pd」「cytochrome P」

「チトクロムP450酵素CYP1A1」

Cytochrome P450, family 1, subfamily A, polypeptide 1
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	4I8V
Identifiers
Symbols	CYP1A1 ; AHH; AHRR; CP11; CYP1; P1-450; P450-C; P450DX
External IDs	OMIM: 108330 MGI: 88588 HomoloGene: 68062 ChEMBL: 2231 GeneCards: CYP1A1 Gene
EC number	1.14.14.1
Gene ontology
Molecular function	• iron ion binding; • protein binding; • steroid hydroxylase activity; • oxidoreductase activity; • oxidoreductase activity, acting on diphenols and related substances as donors; • flavonoid 3'-monooxygenase activity; • oxygen binding; • enzyme binding; • heme binding; • demethylase activity; • aromatase activity; • vitamin D 24-hydroxylase activity;
Cellular component	• mitochondrion; • endoplasmic reticulum membrane;
Biological process	• response to hypoxia; • porphyrin-containing compound metabolic process; • xenobiotic metabolic process; • aging; • cell proliferation; • amine metabolic process; • response to wounding; • response to virus; • response to nematode; • response to herbicide; • embryo development ending in birth or egg hatching; • coumarin metabolic process; • flavonoid metabolic process; • response to iron(III) ion; • insecticide metabolic process; • drug metabolic process; • dibenzo-p-dioxin catabolic process; • arachidonic acid metabolic process; • epoxygenase P450 pathway; • response to food; • response to lipopolysaccharide; • response to vitamin A; • response to immobilization stress; • vitamin D metabolic process; • response to drug; • 9-cis-retinoic acid biosynthetic process; • camera-type eye development; • cellular lipid metabolic process; • small molecule metabolic process; • response to antibiotic; • response to arsenic-containing substance; • digestive tract development; • hydrogen peroxide biosynthetic process; • response to hyperoxia; • oxidation-reduction process; • maternal process involved in parturition; • hepatocyte differentiation; • demethylation; • cellular response to organic cyclic compound; • omega-hydroxylase P450 pathway; • positive regulation of G1/S transition of mitotic cell cycle;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;