CYP3A

• CYP3Aタンパク質

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cytochrome P-450 CYP3A

• cytochrome P-450 CYP3A

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/02/07 22:42:53」(JST)

wiki ja

[Wiki ja表示]

シトクロムP450、ファミリー1、サブファミリーAは、またはCYP3Aとは、ヒトの遺伝子である。

CYP3A遺伝子座は、遺伝子スーパーファミリーのシトクロムP450の3Aサブファミリーのすべての既知のメンバーを含む。これらの遺伝子は、薬物の代謝と、コレステロール、ステロイド、および他の脂質の合成に関わる多くの反応を触媒するモノオキシゲナーゼの一群をコード化している。

CYP3Aクラスターは4種の遺伝子から成る。

• CYP3A4
• CYP3A5
• CYP3A7
• CYP3A43

この領域は2種の偽遺伝子を含む。

• CYP3A5P1
• CYP3A5P2

同様に、いくつかの余分なエクソンを、この領域から生産された転写産物に含んだり、含まなかったりするかもしれない。過去には、別のCYP3Aメンバーの、CYP3A3が存在すると考えられていたが、現在ではこの配列はCYP3A4の転写変異体を表現していると考えられている。

脚注

さらに読む

• Smith G, Stubbins MJ, Harries LW, Wolf CR (1999). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157. 
• Lamba JK, Lin YS, Schuetz EG, Thummel KE (2003). "Genetic contribution to variable human CYP3A-mediated metabolism". Adv. Drug Deliv. Rev. 54 (10): 1271–94. doi:10.1016/S0169-409X(02)00066-2. PMID 12406645. 
• Finta C, Zaphiropoulos PG (2001). "The human cytochrome P450 3A locus. Gene evolution by capture of downstream exons". Gene 260 (1–2): 13–23. doi:10.1016/S0378-1119(00)00470-4. PMID 11137287. 
• Gellner K, Eiselt R, Hustert E et al. (2001). "Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene". Pharmacogenetics 11 (2): 111–21. doi:10.1097/00008571-200103000-00002. PMID 11266076. 
• Miyazawa M, Shindo M, Shimada T (2002). "Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes". Xenobiotica 31 (10): 713–23. doi:10.1080/00498250110065595. PMID 11695850. 
• Reid JM, Kuffel MJ, Ruben SL et al. (2002). "Rat and human liver cytochrome P-450 isoform metabolism of ecteinascidin 743 does not predict gender-dependent toxicity in humans". Clin. Cancer Res. 8 (9): 2952–62. PMID 12231541. 
• Martínez C, García-Martín E, Pizarro RM et al. (2002). "Expression of paclitaxel-inactivating CYP3A activity in human colorectal cancer: implications for drug therapy". Br. J. Cancer 87 (6): 681–6. doi:10.1038/sj.bjc.6600494. PMC 2364247. PMID 12237780. 
• Dowling TC, Briglia AE, Fink JC et al. (2003). "Characterization of hepatic cytochrome p4503A activity in patients with end-stage renal disease". Clin. Pharmacol. Ther. 73 (5): 427–34. doi:10.1016/S0009-9236(03)00056-0. PMID 12732843. 
• Sunman JA, Hawke RL, LeCluyse EL, Kashuba AD (2004). "Kupffer cell-mediated IL-2 suppression of CYP3A activity in human hepatocytes". Drug Metab. Dispos. 32 (3): 359–63. doi:10.1124/dmd.32.3.359. PMID 14977871. 
• Somogyi AA, Menelaou A, Fullston SV (2005). "CYP3A4 mediates dextropropoxyphene N-demethylation to nordextropropoxyphene: human in vitro and in vivo studies and lack of CYP2D6 involvement". Xenobiotica 34 (10): 875–87. doi:10.1080/00498250400008371. PMID 15764408. 
• Thompson EE, Kuttab-Boulos H, Yang L et al. (2006). "Sequence diversity and haplotype structure at the human CYP3A cluster". Pharmacogenomics J. 6 (2): 105–14. doi:10.1038/sj.tpj.6500347. PMID 16314882. 
• Bochud M, Eap CB, Elston RC et al. (2006). "Association of CYP3A5 genotypes with blood pressure and renal function in African families". J. Hypertens. 24 (5): 923–9. doi:10.1097/01.hjh.0000222763.84605.4a. PMID 16612255. 
• Cheung CY, Op den Buijsch RA, Wong KM et al. (2006). "Influence of different allelic variants of the CYP3A and ABCB1 genes on the tacrolimus pharmacokinetic profile of Chinese renal transplant recipients". Pharmacogenomics 7 (4): 563–74. doi:10.2217/14622416.7.4.563. PMID 16753004. 
• Rais N, Chawla YK, Kohli KK (2007). "CYP3A phenotypes and genotypes in North Indians". Eur. J. Clin. Pharmacol. 62 (6): 417–22. doi:10.1007/s00228-006-0105-3. PMID 16758258. 
• Kirby B, Kharasch ED, Thummel KT et al. (2007). "Simultaneous measurement of in vivo P-glycoprotein and cytochrome P450 3A activities". Journal of clinical pharmacology 46 (11): 1313–9. doi:10.1177/0091270006292625. PMID 17050796. 
• He P, Court MH, Greenblatt DJ, von Moltke LL (2007). "Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity". Journal of clinical pharmacology 46 (11): 1356–69. doi:10.1177/0091270006292125. PMID 17050801. 
• Watanabe A, Nakamura K, Okudaira N et al. (2007). "Risk assessment for drug-drug interaction caused by metabolism-based inhibition of CYP3A using automated in vitro assay systems and its application in the early drug discovery process". Drug Metab. Dispos. 35 (7): 1232–8. doi:10.1124/dmd.107.015016. PMID 17392390. 
• Kharasch ED, Walker A, Isoherranen N et al. (2007). "Influence of CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of the cytochrome P4503A probes alfentanil and midazolam". Clin. Pharmacol. Ther. 82 (4): 410–26. doi:10.1038/sj.clpt.6100237. PMID 17554244. 

wiki en

[Wiki en表示]

Cytochrome P450, family 3, subfamily A
Identifiers
Symbols	CYP3A ; CYP3
External IDs	GeneCards: CYP3A Gene
Gene ontology
Orthologs
Species	Human	Mouse
Entrez	1574	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	[1]	n/a

Cytochrome P450, family 3, subfamily A, also known as CYP3A, is a human gene.

The CYP3A locus includes all the known members of the 3A subfamily of the cytochrome P450 superfamily of genes. These genes encode monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The CYP3A cluster consists of four genes:

• CYP3A4
• CYP3A5,
• CYP3A7, and
• CYP3A43.

The region also contains two pseudogenes:

• CYP3A5P1 and
• CYP3A5P2,

as well as several extra exons which may or may not be included in transcripts produced from this region. Previously another CYP3A member, CYP3A3, was thought to exist; however, it is now thought that this sequence represents a transcript variant of CYP3A4.

References

Further reading

• Smith G, Stubbins MJ, Harries LW, Wolf CR (1999). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157. 
• Lamba JK, Lin YS, Schuetz EG, Thummel KE (2003). "Genetic contribution to variable human CYP3A-mediated metabolism". Adv. Drug Deliv. Rev. 54 (10): 1271–94. doi:10.1016/S0169-409X(02)00066-2. PMID 12406645. 
• Finta C, Zaphiropoulos PG (2001). "The human cytochrome P450 3A locus. Gene evolution by capture of downstream exons". Gene 260 (1–2): 13–23. doi:10.1016/S0378-1119(00)00470-4. PMID 11137287. 
• Gellner K, Eiselt R, Hustert E et al. (2001). "Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene". Pharmacogenetics 11 (2): 111–21. doi:10.1097/00008571-200103000-00002. PMID 11266076. 
• Miyazawa M, Shindo M, Shimada T (2002). "Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes". Xenobiotica 31 (10): 713–23. doi:10.1080/00498250110065595. PMID 11695850. 
• Reid JM, Kuffel MJ, Ruben SL et al. (2002). "Rat and human liver cytochrome P-450 isoform metabolism of ecteinascidin 743 does not predict gender-dependent toxicity in humans". Clin. Cancer Res. 8 (9): 2952–62. PMID 12231541. 
• Martínez C, García-Martín E, Pizarro RM et al. (2002). "Expression of paclitaxel-inactivating CYP3A activity in human colorectal cancer: implications for drug therapy". Br. J. Cancer 87 (6): 681–6. doi:10.1038/sj.bjc.6600494. PMC 2364247. PMID 12237780. 
• Dowling TC, Briglia AE, Fink JC et al. (2003). "Characterization of hepatic cytochrome p4503A activity in patients with end-stage renal disease". Clin. Pharmacol. Ther. 73 (5): 427–34. doi:10.1016/S0009-9236(03)00056-0. PMID 12732843. 
• Sunman JA, Hawke RL, LeCluyse EL, Kashuba AD (2004). "Kupffer cell-mediated IL-2 suppression of CYP3A activity in human hepatocytes". Drug Metab. Dispos. 32 (3): 359–63. doi:10.1124/dmd.32.3.359. PMID 14977871. 
• Somogyi AA, Menelaou A, Fullston SV (2005). "CYP3A4 mediates dextropropoxyphene N-demethylation to nordextropropoxyphene: human in vitro and in vivo studies and lack of CYP2D6 involvement". Xenobiotica 34 (10): 875–87. doi:10.1080/00498250400008371. PMID 15764408. 
• Thompson EE, Kuttab-Boulos H, Yang L et al. (2006). "Sequence diversity and haplotype structure at the human CYP3A cluster". Pharmacogenomics J. 6 (2): 105–14. doi:10.1038/sj.tpj.6500347. PMID 16314882. 
• Bochud M, Eap CB, Elston RC et al. (2006). "Association of CYP3A5 genotypes with blood pressure and renal function in African families". J. Hypertens. 24 (5): 923–9. doi:10.1097/01.hjh.0000222763.84605.4a. PMID 16612255. 
• Cheung CY, Op den Buijsch RA, Wong KM et al. (2006). "Influence of different allelic variants of the CYP3A and ABCB1 genes on the tacrolimus pharmacokinetic profile of Chinese renal transplant recipients". Pharmacogenomics 7 (4): 563–74. doi:10.2217/14622416.7.4.563. PMID 16753004. 
• Rais N, Chawla YK, Kohli KK (2007). "CYP3A phenotypes and genotypes in North Indians". Eur. J. Clin. Pharmacol. 62 (6): 417–22. doi:10.1007/s00228-006-0105-3. PMID 16758258. 
• Kirby B, Kharasch ED, Thummel KT et al. (2007). "Simultaneous measurement of in vivo P-glycoprotein and cytochrome P450 3A activities". Journal of clinical pharmacology 46 (11): 1313–9. doi:10.1177/0091270006292625. PMID 17050796. 
• He P, Court MH, Greenblatt DJ, von Moltke LL (2007). "Human pregnane X receptor: genetic polymorphisms, alternative mRNA splice variants, and cytochrome P450 3A metabolic activity". Journal of clinical pharmacology 46 (11): 1356–69. doi:10.1177/0091270006292125. PMID 17050801. 
• Watanabe A, Nakamura K, Okudaira N et al. (2007). "Risk assessment for drug-drug interaction caused by metabolism-based inhibition of CYP3A using automated in vitro assay systems and its application in the early drug discovery process". Drug Metab. Dispos. 35 (7): 1232–8. doi:10.1124/dmd.107.015016. PMID 17392390. 
• Kharasch ED, Walker A, Isoherranen N et al. (2007). "Influence of CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of the cytochrome P4503A probes alfentanil and midazolam". Clin. Pharmacol. Ther. 82 (4): 410–26. doi:10.1038/sj.clpt.6100237. PMID 17554244. 

UpToDate Contents

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English Journal

• Enhanced intestinal absorption of etoposide by self-microemulsifying drug delivery systems: Roles of P-glycoprotein and cytochrome P450 3A inhibition.

• Zhao G, Huang J, Xue K, Si L, Li G.SourceSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
• European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2013 Nov 20;50(3-4):429-39. doi: 10.1016/j.ejps.2013.08.016. Epub 2013 Aug 25.
• Etoposide is recognized as a dual P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) substrate drug with poor water-solubility. To improve its solubility and bioavailability, three novel self-microemulsifying drug delivery systems (SMEDDS) contained the known P-gp and CYP3A inhibitory surfactants,
• PMID 23981337

• A semi-physiologically-based pharmacokinetic model characterizing mechanism-based auto-inhibition to predict stereoselective pharmacokinetics of verapamil and its metabolite norverapamil in human.

• Wang J, Xia S, Xue W, Wang D, Sai Y, Liu L, Liu X.SourceKey Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China; Department of Drug Metabolism and Pharmacokinetics, Hutchison Medipharma Ltd., Shanghai, China.
• European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2013 Nov 20;50(3-4):290-302. doi: 10.1016/j.ejps.2013.07.012. Epub 2013 Jul 31.
• Verapamil and its major metabolite norverapamil were identified to be both mechanism-based inhibitors and substrates of CYP3A and reported to have non-linear pharmacokinetics in clinic. Metabolic clearances of verapamil and norverapmil as well as their effects on CYP3A activity were firstly measured
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• CYP2J2 and CYP2C19 Are the Major Enzymes Responsible for Metabolism of Albendazole and Fenbendazole in Human Liver Microsomes and Recombinant P450 Assay Systems.

• Wu Z, Lee D, Joo J, Shin JH, Kang W, Oh S, Lee do Y, Lee SJ, Yea SS, Lee HS, Lee T, Liu KH.SourceCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Korea.
• Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2013 Nov;57(11):5448-56. doi: 10.1128/AAC.00843-13. Epub 2013 Aug 19.
• Albendazole and fenbendazole are broad-spectrum anthelmintics that undergo extensive metabolism to form hydroxyl and sulfoxide metabolites. Although CYP3A and flavin-containing monooxygenase have been implicated in sulfoxide metabolite formation, the enzymes responsible for hydroxyl metabolite forma
• PMID 23959307

Japanese Journal

• Co-administration of Fluvastatin and CYP3A4 and CYP2C8 Inhibitors May Increase the Exposure to Fluvastatin in Carriers of CYP2C9 Genetic Variants

• Biological & pharmaceutical bulletin 40(7), 1078-1085, 2017-07
• NAID 40021233975

• Joint toxicity of fluoroquinolone and tetracycline antibiotics to zebrafish (Danio rerio) based on biochemical biomarkers and histopathological observation

• The Journal of toxicological sciences : an official journal of the Japanese Society of Toxicology 42(3), 267-280, 2017-06
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• 副作用・薬物相互作用トレンドチェック 注目論文を読み解く(61)

• 医薬ジャーナル 53(5), 150-156, 2017-05
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Related Links

• CYP - 薬学用語解説 - 日本薬学会

当サイトの掲載情報の正確性については万全を期しておりますが、本会は利用者 が当サイトの情報を用いて行う一切の行為について何ら責任を負うものではありません。 CYP

• 株式会社chromocenter - ヒト薬物代謝モデル動物

薬物代謝関連酵素のうち、CYP3Aは上市されている医薬品の約40%の代謝に関連することが知られており、ヒト型化が望まれていました。しかし、ヒトのCYP3A遺伝子群 (CYP3A5, CYP3A7, CYP3A4, CYP3A43) は 7番染色体上に約 ...

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• CYP3A

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チトクロムP450酵素CYP3A

「チトクロムP450酵素CYP3A」

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cytochrome P-450 CYP3A

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CYP3Aタンパク質

「cytochrome P-450 CYP3A」

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チトクロムP450酵素CYP3A

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CYP3A