Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/12 08:01:17」(JST)

wiki en

Cytochrome P450 2E1 (abbreviated CYP2E1, EC 1.14.13.n7), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. In humans, the CYP2E1 enzyme is encoded by the CYP2E1 gene.^[1] While it is involved in the oxidative metabolism of a small range of substrates (mostly small polar molecules), there are many important drug interactions mediated by CYP2E1.

Function

Most drugs undergo deactivation by CYP2E1, either directly or by facilitated excretion from the body. Also, many substances are bioactivated by CYP2E1 to form their active compounds (for examples - see table below)

CYP2E1, as well as alcohol dehydrogenase and aldehyde dehydrogenase, is an important enzyme for the conversion of ethanol to acetaldehyde and to acetate in humans.^[2]

In the conversion sequence of acetyl-CoA to glucose, CYP2E1 transforms acetone via hydroxyacetone (acetol) into propylene glycol and methylglyoxal, the precursors of pyruvate, acetate and lactate.^[3]^[4]^[5]

Ligands

Following is a table of selected substrates, inducers and inhibitors of CYP2E1. Where classes of agents are listed, there may be exceptions within the class.

**Selected inducers, inhibitors and substrates of CYP2E1**
Substrates	Inhibitors	Inducers
anaesthetics: halothane^[6]^[7] enflurane^[6]^[7] isoflurane^[7] methoxyflurane^[7] sevoflurane^[7] paracetamol^[6] (acetaminophen) - used as analgesic, antipyretic - toxication by CYP2E1^[7] ethanol^[6]^[7] (psychoactive) Industrial potentially toxic substances aniline^[7] benzene^[7] dimethylformamide^[7] theophylline^[7] (stimulant, active metabolite of caffeine) chlorzoxazone^[7] (muscle relaxant) Zopiclone and Eszopiclone (sedative/hypnotics)	diethyldithiocarbamate^[6] (in cancer) disulfiram^[7] (in alcoholism)	ethanol^[7] (psychoactive) isoniazid^[7] (in tuberculosis) tobacco smoking^[8]

Regulation

Within one day of birth, the rat hepatic CYP2E1 gene is activated transcriptionally. CYP2E1 expression is easily inducible. It seems that there exist two stages of induction, a posttranslational mechanism for increased protein stability at low levels of ethanol and an additional transcriptional induction at high levels of ethanol.^[9]

Applications

Trees have been genetically engineered to overexpress the CYP2E1 enzyme. These transgenic trees have been used to remove pollutants from groundwater, a process known as phytoremediation.^[10]

References

^ Kölble K (Dec 1993). "Regional mapping of short tandem repeats on human chromosome 10: cytochrome P450 gene CYP2E, D10S196, D10S220, and D10S225". Genomics 18 (3): 702–4. doi:10.1016/S0888-7543(05)80378-7. PMID 8307581.
^ Hayashi S, Watanabe J, Kawajiri K (Oct 1991). "Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene". Journal of Biochemistry 110 (4): 559–65. PMID 1778977.
^ Glew, Robert H. "You Can Get There From Here: Acetone, Anionic Ketones and Even-Carbon Fatty Acids can Provide Substrates for Gluconeogenesis". Retrieved August 2013.
^ Miller ON, Bazzano G (Jul 1965). "Propanediol metabolism and its relation to lactic acid metabolism". Annals of the New York Academy of Sciences 119 (3): 957–973. Bibcode:1965NYASA.119..957M. doi:10.1111/j.1749-6632.1965.tb47455.x. PMID 4285478.
^ Ruddick JA (1972). "Toxicology, metabolism, and biochemistry of 1,2-propanediol". Toxicol App Pharmacol 21: 102–111. doi:10.1016/0041-008X(72)90032-4.
^ ^a ^b ^c ^d ^e Swedish environmental classification of pharmaceuticals Facts for prescribers (Fakta för förskrivare)
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o Flockhart DA (2007). "Drug Interactions: Cytochrome P₄₅₀ Drug Interaction Table". Indiana University School of Medicine. Retrieved on July 2011
^ Desai HD, Seabolt J, Jann MW (2001). "Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective". CNS Drugs 15 (6): 469–494. doi:10.2165/00023210-200115060-00005. PMID 11524025.
^ Lieber CS (Jun 1999). "Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968-1998)--a review". Alcoholism, Clinical and Experimental Research 23 (6): 991–1007. doi:10.1111/j.1530-0277.1999.tb04217.x. PMID 10397283.
^ Doty SL, James CA, Moore AL, Vajzovic A, Singleton GL, Ma C, Khan Z, Xin G, Kang JW, Park JY, Meilan R, Strauss SH, Wilkerson J, Farin F, Strand SE (Oct 2007). "Enhanced phytoremediation of volatile environmental pollutants with transgenic trees". Proceedings of the National Academy of Sciences of the United States of America 104 (43): 16816–21. Bibcode:2007PNAS..10416816D. doi:10.1073/pnas.0703276104. PMC 2040402. PMID 17940038.

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. 薬と肝臓：代謝および肝障害の機序 drugs and the liver metabolism and mechanisms of injury
2. イソニアジド肝毒性 isoniazid hepatotoxicity
3. ハロタン肝炎 halothane hepatitis
4. 成人におけるアセトアミノフェン（パラセタモール）中毒：病態生理、症状、および診断 acetaminophen paracetamol poisoning in adults pathophysiology presentation and diagnosis
5. 小児および思春期の患者におけるアセトアミノフェン（パラセタモール）中毒の臨床症状および診断 clinical manifestations and diagnosis of acetaminophen paracetamol poisoning in children and adolescents

English Journal

Improvement and validation of a medium-term gpt delta rat model for predicting chemical carcinogenicity and underlying mode of action.

Matsushita K1, Kuroda K1, Ishii Y1, Takasu S1, Kijima A1, Kawaguchi H2, Miyoshi N2, Nohmi T3, Ogawa K1, Nishikawa A3, Umemura T4.
Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie.Exp Toxicol Pathol.2014 Sep;66(7):313-21. doi: 10.1016/j.etp.2014.05.002. Epub 2014 Jun 11.
We have developed a new medium-term animal model, "GPG", in which an in vivo mutation assay in partially hepatectomized tissue and a tumor-promoting assay were performed. The tumor-promoting assay measures glutathione S-transferase placental form positive foci induced by diethylnitrosamine (DEN) in
PMID 24929978

Inhibition of cytochrome P450 by ethambutol in human liver microsomes.

Lee SY1, Jang H1, Lee JY1, Kwon KI1, Oh SJ2, Kim SK3.
Toxicology letters.Toxicol Lett.2014 Aug 17;229(1):33-40. doi: 10.1016/j.toxlet.2014.06.006. Epub 2014 Jun 5.
Although cytochrome P450 inhibition is the major drug-drug interaction (DDI) mechanism in clinical pharmacotherapy, DDI of a number of well-established drugs have not been investigated. Rifampicin, isoniazid, pyrazinamide and ethambutol combination therapy inhibits clearance of theophylline in patie
PMID 24910189

Phenotyping of CYP450 in human liver microsomes using the cocktail approach.

Spaggiari D1, Geiser L, Daali Y, Rudaz S.
Analytical and bioanalytical chemistry.Anal Bioanal Chem.2014 Aug;406(20):4875-87. doi: 10.1007/s00216-014-7915-4. Epub 2014 Jun 4.
The cocktail approach is an advantageous strategy used to monitor the activities of several cytochromes P450 (CYPs) in a single test to increase the throughput of in vitro phenotyping studies. In this study, a cocktail mixture was developed with eight CYP-specific probe substrates to simultaneously
PMID 24894520

Japanese Journal

Purple potato (Solanum tuberosum L.) anthocyanins attenuate alcohol-induced hepatic injury by enhancing antioxidant defense

Journal of natural medicines 70(1), 45-53, 2016
NAID 40020680897

Requirements for human iPS cell-derived hepatocytes as an alternative to primary human hepatocytes for assessing absorption, distribution, metabolism, excretion and toxicity of pharmaceuticals

Fundamental Toxicological Sciences 3(3), 89-99, 2016
NAID 130005144692

非アルコール性脂肪肝炎を来す薬剤

YAKUGAKU ZASSHI 136(4), 579-582, 2016
NAID 130005140771

Related Pictures

Source: ANN IST SUPER SANITÀ 2006, VOL 450 Enzyme System (systeme cytochrome p450 CYP2E1 and oxidant stress in alcoholic and CYP2E1 activities associated with hepatic CYP2E1 Figura 2 . Participación de CYP2E1 en el Gene specific modifications unravel Figure 1 : Molecular mechanisms of alcohol

★リンクテーブル★

拡張検索	「CYP2E1タンパク質」「チトクロムP450酵素CYP2E1」「cytochrome P-450 CYP2E1」

「CYP2E1タンパク質」

Cytochrome P450, family 2, subfamily E, polypeptide 1
	Rendering based on PDB 3E4E.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	3E4E, 3E6I, 3GPH, 3KOH, 3LC4, 3T3Z
Identifiers
Symbols	CYP2E1 ; CPE1; CYP2E; P450-J; P450C2E
External IDs	OMIM: 124040 MGI: 88607 HomoloGene: 68089 ChEMBL: 5281 GeneCards: CYP2E1 Gene
EC number	1.14.13.n7
Gene ontology
Molecular function	• monooxygenase activity; • iron ion binding; • arachidonic acid epoxygenase activity; • steroid hydroxylase activity; • oxidoreductase activity; • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen; • 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; • oxygen binding; • enzyme binding; • heme binding;
Cellular component	• Golgi membrane; • cytoplasm; • mitochondrion; • endoplasmic reticulum membrane; • intrinsic component of endoplasmic reticulum membrane; • intracellular membrane-bounded organelle;
Biological process	• triglyceride metabolic process; • xenobiotic metabolic process; • steroid metabolic process; • response to ozone; • response to organonitrogen compound; • monoterpenoid metabolic process; • drug metabolic process; • epoxygenase P450 pathway; • exogenous drug catabolic process; • small molecule metabolic process; • response to ethanol; • heterocycle metabolic process; • oxidation-reduction process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;