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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].

References

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  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]
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  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]
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  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]
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