CYP2E1

Cytochrome P450, family 2, subfamily E, polypeptide 1
Rendering based on PDB 3E4E.
Available structures PDB 3E4E, 3E6I, 3GPH, 3KOH, 3LC4
Identifiers
Symbols	CYP2E1; CPE1; CYP2E; P450-J; P450C2E
External IDs	OMIM: 124040 MGI: 88607 HomoloGene: 68089 GeneCards: CYP2E1 Gene
EC number	1.14.14.1
Gene Ontology Molecular function • monooxygenase activity • electron carrier activity • oxidoreductase activity • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NADH or NADPH 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 • oxygen binding • enzyme binding • heme binding • metal ion binding Cellular component • endoplasmic reticulum • endoplasmic reticulum membrane • endoplasmic reticulum membrane • microsome • membrane Biological process • xenobiotic metabolic process • steroid metabolic process • monoterpenoid metabolic process • drug metabolic process • drug metabolic process • heterocycle metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1571	13106
Ensembl	ENSG00000130649	ENSMUSG00000025479
UniProt	P05181	Q05421
RefSeq (mRNA)	NM_000773.3	NM_021282.2
RefSeq (protein)	NP_000764.1	NP_067257.1
Location (UCSC)	Chr 10: 135.33 – 135.37 Mb	Chr 7: 147.95 – 147.96 Mb
PubMed search	[1]	[2]

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.

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]

CYP2E1 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[3][4] enflurane[3][4] isoflurane[4] methoxyflurane[4] sevoflurane[4] paracetamol[3] (analgesic, antipyretic) - toxication by CYP2E1[4] ethanol[3][4] (psychoactive) Industrial potentially toxic substances aniline[4] benzene[4] dimethylformamide[4] theophylline[4] (stimulant) chlorzoxazone[4] (muscle relaxant)	diethyldithiocarbamate[3] (in cancer) disulfiram[4] (in alcoholism)	ethanol[4] (psychoactive) isoniazid[4] (in tuberculosis)

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.^[5]

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.^[6]

See also

• cytochrome
• metabolism

References

1. ^ Kölble K (December 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. 
2. ^ Hayashi S, Watanabe J, Kawajiri K (October 1991). "Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene". J. Biochem. 110 (4): 559–65. PMID 1778977. 
3. ^ ^{a b c d e} Swedish environmental classification of pharmaceuticals Facts for prescribers (Fakta för förskrivare)
4. ^ ^{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. http://medicine.iupui.edu/flockhart/table.htm.  Retrieved on July 2011
5. ^ Lieber CS (June 1999). "Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968-1998)--a review". Alcohol. Clin. Exp. Res. 23 (6): 991–1007. doi:10.1111/j.1530-0277.1999.tb04217.x. PMID 10397283. 
6. ^ 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 (October 2007). "Enhanced phytoremediation of volatile environmental pollutants with transgenic trees". Proc. Natl. Acad. Sci. U.S.A. 104 (43): 16816–21. doi:10.1073/pnas.0703276104. PMC 2040402. PMID 17940038. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2040402. 

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. 
• Kessova I, Cederbaum AI (2003). "CYP2E1: biochemistry, toxicology, regulation and function in ethanol-induced liver injury". Curr. Mol. Med. 3 (6): 509–18. doi:10.2174/1566524033479609. PMID 14527082. 
• Webb A, Lind PA, Kalmijn J, Feiler HS, Smith TL, Schuckit MA, Wilhelmsen K (2011). "The Investigation into CYP2E1 in Relation to the Level of Response to Alcohol Through a Combination of Linkage and Association Analysis". Alcoholism: Clinical and Experimental Research 35 (1): 10–18. doi:10.1111/j.1530-0277.2010.01317.x.