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Gene Review

CYP2E1  -  cytochrome P450, family 2, subfamily E,...

Homo sapiens

Synonyms: 4-nitrophenol 2-hydroxylase, CPE1, CYP2E, CYPIIE1, Cytochrome P450 2E1, ...
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Disease relevance of CYP2E1

  • The distribution of genotypes in CYP2E1-intron 6 was significantly different between the control group and all lymphomas (P = 0.03), patients with NHL (P = 0.024), and especially aggressive diffuse NHL (P = 0.007) [1].
  • Thus, besides perturbing the homeostasis of hepatocytes, CYP2E1-derived diffusible oxidants may also interact with stellate cells and contribute to hepatic fibrosis [2].
  • The aim of this study was to evaluate whether the polymorphism of the CYP2E1 gene is associated with antituberculosis drug-induced hepatitis [3].
  • This study was prompted by the finding that toxicity in CYP2E1-overexpressing cells was markedly enhanced after GSH depletion by buthionine sulfoximine treatment [4].
  • A very similar distribution was found for CYP2E1 in FGC4 cells, and immunoprecipitation experiments performed in cultures of FGC4-related Fao hepatoma cells suggest that surface immunoreactivity originates from a small fraction of intact CYP2E1 apoprotein [5].

Psychiatry related information on CYP2E1


High impact information on CYP2E1


Chemical compound and disease context of CYP2E1


Biological context of CYP2E1


Anatomical context of CYP2E1


Associations of CYP2E1 with chemical compounds


Physical interactions of CYP2E1

  • The FANCG Fanconi anemia protein interacts with CYP2E1: possible role in protection against oxidative DNA damage [23].
  • ESR experiments indicated the formation of stable heme-NO complexes with CYP2E1 [24].
  • A polymorphism of CYP2E1 detectable by the restriction enzyme Rsa I may be functionally important because it is located in a putative binding site for the transcription factor HNF-1 and has been associated with higher levels of CYP2E1 transcription [25].

Enzymatic interactions of CYP2E1

  • These data suggest that in control mice CYP2E1 catalyzes the bulk of protein binding, whereas CYP2D catalyzes slightly more cysteine conjugation than does CYP2E1 [26].
  • With 36 different substrate concentrations in these two reactions, coumarin 7-hydroxylation was found to be catalyzed mainly by a single enzyme CYP2A6 and 7-ethoxycoumarin was oxidized by at least two enzymes CYP2E1 and CYP1A2 in human liver microsomes [27].
  • In contrast, CYP2E1 appears to be the main enzyme involved in the low affinity components of CA N1- and N7-demethylation while CA 8-hydroxylation is catalysed predominantly by a CYP3A isoform(s) [28].
  • Recombinant rat CYP2E1 catalyzed TCE metabolism to CH with greater affinity than did the recombinant P450 enzymes, rat CYP2F4, mouse CYP2F2, rat CYP2B1, and human CYP2E1 [29].
  • Sixteen healthy non-smoking subjects, two females and 14 males, were exposed to three different types of diets and afterwards assayed for CYP1A2 catalysed caffeine metabolites and for CYP2E1 catalysed 6-hydroxylation of chlorzoxazone [30].

Regulatory relationships of CYP2E1

  • METHODS: The involvement of CYP2E1 was assessed through pretreatment of adult human volunteers with disulfiram to inhibit the enzyme and the role of CYP3A4 through its induction in a second cohort of adults with rifampin (INN, rifampicin) [20].
  • CYP2A6/2A7 mRNA was expressed in 61% and CYP2E1 mRNA in 96% of the patients, but in the latter a lower degree of inter-individual variation was observed [31].
  • Polyinosinic acid-polycytidylic acid down regulated the constitutive and pyridine-induced expression of CYP2E1 and the pyridine- and beta-naphthoflavone-induced expression of CYP1A1 as demonstrated by metabolic activity and immunoblot analyses [32].
  • The chemical inhibitors ketoconazole (CYP3A) and 7-EFC (CYP2B6) inhibited both 2- and 3-hydroxycarbamazepine formation whereas 4-methylpyrazole (CYP2E1) markedly decreased 2-hydroxycarbamazepine formation [33].
  • No differences were found in the prevalences of the GSTM1 and GSTT1 null genotypes between alcoholics and the controls and no association was found between the rare CYP2E1 c2 allele and liver cirrhosis and pancreatitis [34].

Other interactions of CYP2E1

  • Western blotting confirmed abundant expression of these CYP4 proteins in human kidney and revealed that other AA-oxidizing P450s, including CYP2C8, CYP2C9, and CYP2E1, were not expressed [35].
  • DTIC N-demethylation in a panel of 10 human liver microsome preparations was correlated with the catalytic activities for CYP1A2 (ethoxyresorufin O-deethylation and caffeine N3-demethylation) in the absence of alpha-naphthoflavone and with the catalytic activities for CYP2E1 (chlorzoxazone 6-hydroxylations) in the presence of alpha-naphthoflavone [36].
  • DTIC metabolism was catalyzed by recombinant human CYP1A1, CYP1A2, and CYP2E1 [36].
  • RESULTS: Comparisons of presupplementation and postsupplementation ratios indicated that St John's wort significantly induced the activity of CYP2E1 and CYP3A4 (P <.0001) [37].
  • These forms were present also in the reduction samples, with CYP2E1 and CYP1B1 being detected in all samples [38].

Analytical, diagnostic and therapeutic context of CYP2E1

  • Case-control studies that have investigated the association between alcoholism and alcohol-induced liver damage and the ADH2, ADH3, CYP2E1, and ADLH2 polymorphisms have reported controversial or inconclusive results [39].
  • The increase in collagen production by coculture with E47 cells was prevented by antioxidants, by CYP2E1 inhibitors, and by transfected antisense CYP2E1 [2].
  • In this study, we used quantitative RT-PCR to evaluate expression of CYP2A6 and CYP2E1 in primary human BECs from 12 non-smokers and eight smokers [40].
  • Utilizing mAb 1-12-3, the human liver microsomal samples displayed an immunoblotting profile matching that obtained from a microsomal preparation from a AHH-1 TK+/- cell line expressing solely human CYP1A1 and differing from the profile obtained using a polyclonal antibody directed against CYP2E1 and cells expressing CYP2E1 [41].
  • Genomic DNA samples were assayed for restriction fragment length polymorphisms in the CYP2E1 and GSTP1 loci by PCR amplification followed by digestion with RsaI and Alw26I, respectively [42].


  1. Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas. Sarmanová, J., Benesová, K., Gut, I., Nedelcheva-Kristensen, V., Tynková, L., Soucek, P. Hum. Mol. Genet. (2001) [Pubmed]
  2. Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1-derived reactive oxygen species. Nieto, N., Friedman, S.L., Cederbaum, A.I. Hepatology (2002) [Pubmed]
  3. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Huang, Y.S., Chern, H.D., Su, W.J., Wu, J.C., Chang, S.C., Chiang, C.H., Chang, F.Y., Lee, S.D. Hepatology (2003) [Pubmed]
  4. CYP2E1 overexpression in HepG2 cells induces glutathione synthesis by transcriptional activation of gamma-glutamylcysteine synthetase. Marí, M., Cederbaum, A.I. J. Biol. Chem. (2000) [Pubmed]
  5. Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis. Eliasson, E., Kenna, J.G. Mol. Pharmacol. (1996) [Pubmed]
  6. Biomonitoring of exposure to urban air pollutants: analysis of sister chromatid exchanges and DNA lesions in peripheral lymphocytes of traffic policemen. Carere, A., Andreoli, C., Galati, R., Leopardi, P., Marcon, F., Rosati, M.V., Rossi, S., Tomei, F., Verdina, A., Zijno, A., Crebelli, R. Mutat. Res. (2002) [Pubmed]
  7. Esophageal cancer risk by ALDH2 and ADH2 polymorphisms and alcohol consumption: exploration of gene-environment and gene-gene interactions. Yang, C.X., Matsuo, K., Ito, H., Hirose, K., Wakai, K., Saito, T., Shinoda, M., Hatooka, S., Mizutani, K., Tajima, K. Asian Pac. J. Cancer Prev. (2005) [Pubmed]
  8. Plasma membrane hydroxyethyl radical adducts cause antibody-dependent cytotoxicity in rat hepatocytes exposed to alcohol. Clot, P., Parola, M., Bellomo, G., Dianzani, U., Carini, R., Tabone, M., Aricò, S., Ingelman-Sundberg, M., Albano, E. Gastroenterology (1997) [Pubmed]
  9. Low doses of nicotine and ethanol induce CYP2E1 and chlorzoxazone metabolism in rat liver. Howard, L.A., Micu, A.L., Sellers, E.M., Tyndale, R.F. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  10. Association studies of polymorphisms of CYP2E1 gene in alcoholics with cirrhosis, antisocial personality, and normal controls. Parsian, A., Cloninger, C.R., Zhang, Z.H. Alcohol. Clin. Exp. Res. (1998) [Pubmed]
  11. Oxidative stress, toxicology, and pharmacology of CYP2E1. Caro, A.A., Cederbaum, A.I. Annu. Rev. Pharmacol. Toxicol. (2004) [Pubmed]
  12. The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin. Sarich, T., Kalhorn, T., Magee, S., al-Sayegh, F., Adams, S., Slattery, J., Goldstein, J., Nelson, S., Wright, J. Clin. Pharmacol. Ther. (1997) [Pubmed]
  13. Cytochromes P450 2A6, 2E1, and 3A and production of protein-aldehyde adducts in the liver of patients with alcoholic and non-alcoholic liver diseases. Niemelä, O., Parkkila, S., Juvonen, R.O., Viitala, K., Gelboin, H.V., Pasanen, M. J. Hepatol. (2000) [Pubmed]
  14. Susceptibility to esophageal cancer and genetic polymorphisms in glutathione S-transferases T1, P1, and M1 and cytochrome P450 2E1. Lin, D.X., Tang, Y.M., Peng, Q., Lu, S.X., Ambrosone, C.B., Kadlubar, F.F. Cancer Epidemiol. Biomarkers Prev. (1998) [Pubmed]
  15. Influence of polymorphisms of the human glutathione transferases and cytochrome P450 2E1 enzyme on the metabolism and toxicity of ethylene oxide and acrylonitrile. Thier, R., Balkenhol, H., Lewalter, J., Selinski, S., Dommermuth, A., Bolt, H.M. Mutat. Res. (2001) [Pubmed]
  16. Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis. Chalasani, N., Gorski, J.C., Asghar, M.S., Asghar, A., Foresman, B., Hall, S.D., Crabb, D.W. Hepatology (2003) [Pubmed]
  17. Human lung carcinogen-DNA adduct levels mediated by genetic polymorphisms in vivo. Kato, S., Bowman, E.D., Harrington, A.M., Blomeke, B., Shields, P.G. J. Natl. Cancer Inst. (1995) [Pubmed]
  18. Induction of catalase, alpha, and microsomal glutathione S-transferase in CYP2E1 overexpressing HepG2 cells and protection against short-term oxidative stress. Marí, M., Cederbaum, A.I. Hepatology (2001) [Pubmed]
  19. Development of human cytochrome P450-expressing cell lines: application in mutagenicity testing of ochratoxin A. de Groene, E.M., Hassing, I.G., Blom, M.J., Seinen, W., Fink-Gremmels, J., Horbach, G.J. Cancer Res. (1996) [Pubmed]
  20. Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Manyike, P.T., Kharasch, E.D., Kalhorn, T.F., Slattery, J.T. Clin. Pharmacol. Ther. (2000) [Pubmed]
  21. Oxidation of 1,2-epoxy-3-butene to 1,2:3,4-diepoxybutane by cDNA-expressed human cytochromes P450 2E1 and 3A4 and human, mouse and rat liver microsomes. Seaton, M.J., Follansbee, M.H., Bond, J.A. Carcinogenesis (1995) [Pubmed]
  22. Cytochrome P450 2E1 responsiveness in the promoter of glutamate-cysteine ligase catalytic subunit. Nieto, N., Marí, M., Cederbaum, A.I. Hepatology (2003) [Pubmed]
  23. The FANCG Fanconi anemia protein interacts with CYP2E1: possible role in protection against oxidative DNA damage. Futaki, M., Igarashi, T., Watanabe, S., Kajigaya, S., Tatsuguchi, A., Wang, J., Liu, J.M. Carcinogenesis (2002) [Pubmed]
  24. Inhibition of rat and human cytochrome P4502E1 catalytic activity and reactive oxygen radical formation by nitric oxide. Gergel, D., Misík, V., Riesz, P., Cederbaum, A.I. Arch. Biochem. Biophys. (1997) [Pubmed]
  25. Lung cancer risk in relation to the CYP2E1 Rsa I genetic polymorphism among African-Americans and Caucasians in Los Angeles County. London, S.J., Daly, A.K., Cooper, J., Carpenter, C.L., Navidi, W.C., Ding, L., Idle, J.R. Pharmacogenetics (1996) [Pubmed]
  26. Catalysis of the cysteine conjugation and protein binding of acetaminophen by microsomes from a human lymphoblast line transfected with the cDNAs of various forms of human cytochrome P450. Zhou, L., Erickson, R.R., Hardwick, J.P., Park, S.S., Wrighton, S.A., Holtzman, J.L. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  27. Highly sensitive high-performance liquid chromatographic assay for coumarin 7-hydroxylation and 7-ethoxycoumarin O-deethylation by human liver cytochrome P450 enzymes. Yamazaki, H., Tanaka, M., Shimada, T. J. Chromatogr. B Biomed. Sci. Appl. (1999) [Pubmed]
  28. Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoforms. Tassaneeyakul, W., Birkett, D.J., McManus, M.E., Tassaneeyakul, W., Veronese, M.E., Andersson, T., Tukey, R.H., Miners, J.O. Biochem. Pharmacol. (1994) [Pubmed]
  29. Pulmonary bioactivation of trichloroethylene to chloral hydrate: relative contributions of CYP2E1, CYP2F, and CYP2B1. Forkert, P.G., Baldwin, R.M., Millen, B., Lash, L.H., Putt, D.A., Shultz, M.A., Collins, K.S. Drug Metab. Dispos. (2005) [Pubmed]
  30. Effects of dietary broccoli on human in vivo drug metabolizing enzymes: evaluation of caffeine, oestrone and chlorzoxazone metabolism. Kall, M.A., Vang, O., Clausen, J. Carcinogenesis (1996) [Pubmed]
  31. CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter-individual variation in expression and relevance to nitrosamine metabolism. Godoy, W., Albano, R.M., Moraes, E.G., Pinho, P.R., Nunes, R.A., Saito, E.H., Higa, C., Filho, I.M., Kruel, C.D., Schirmer, C.C., Gurski, R., Lang, M.A., Pinto, L.F. Carcinogenesis (2002) [Pubmed]
  32. Regulation of cytochrome P-4501A and cytochrome P-4502E induction in the rat during the production of interferon alpha/beta. Cribb, A.E., Delaporte, E., Kim, S.G., Novak, R.F., Renton, K.W. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  33. Pathways of carbamazepine bioactivation in vitro I. Characterization of human cytochromes P450 responsible for the formation of 2- and 3-hydroxylated metabolites. Pearce, R.E., Vakkalagadda, G.R., Leeder, J.S. Drug Metab. Dispos. (2002) [Pubmed]
  34. Polymorphisms in glutathione S-transferases GSTM1, GSTT1 and GSTP1 and cytochromes P450 CYP2E1 and CYP1A1 and susceptibility to cirrhosis or pancreatitis in alcoholics. Burim, R.V., Canalle, R., Martinelli, A.d.e. .L., Takahashi, C.S. Mutagenesis (2004) [Pubmed]
  35. Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11. Lasker, J.M., Chen, W.B., Wolf, I., Bloswick, B.P., Wilson, P.D., Powell, P.K. J. Biol. Chem. (2000) [Pubmed]
  36. Metabolic activation of dacarbazine by human cytochromes P450: the role of CYP1A1, CYP1A2, and CYP2E1. Reid, J.M., Kuffel, M.J., Miller, J.K., Rios, R., Ames, M.M. Clin. Cancer Res. (1999) [Pubmed]
  37. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Gurley, B.J., Gardner, S.F., Hubbard, M.A., Williams, D.K., Gentry, W.B., Cui, Y., Ang, C.Y. Clin. Pharmacol. Ther. (2002) [Pubmed]
  38. Characterization of cytochrome P450 enzymes in human breast tissue from reduction mammaplasties. Hellmold, H., Rylander, T., Magnusson, M., Reihnér, E., Warner, M., Gustafsson, J.A. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  39. Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease? Zintzaras, E., Stefanidis, I., Santos, M., Vidal, F. Hepatology (2006) [Pubmed]
  40. Measurement of cytochrome P450 2A6 and 2E1 gene expression in primary human bronchial epithelial cells. Crawford, E.L., Weaver, D.A., DeMuth, J.P., Jackson, C.M., Khuder, S.A., Frampton, M.W., Utell, M.J., Thilly, W.G., Willey, J.C. Carcinogenesis (1998) [Pubmed]
  41. Detection of CYP1A1 protein in human liver and induction by TCDD in precision-cut liver slices incubated in dynamic organ culture. Drahushuk, A.T., McGarrigle, B.P., Larsen, K.E., Stegeman, J.J., Olson, J.R. Carcinogenesis (1998) [Pubmed]
  42. Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China. Tan, W., Song, N., Wang, G.Q., Liu, Q., Tang, H.J., Kadlubar, F.F., Lin, D.X. Cancer Epidemiol. Biomarkers Prev. (2000) [Pubmed]
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