Cytochrome P450 2E1 (abbreviated CYP2E1, EC1.14.13.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 CYP2E1gene. 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)
This important enzyme has allowed for the North Americans of Europe to have demonstrably higher alcohol tolerance than their First Nations counterpart. The result of evolution has allowed for a decreased likelihood of developing alcoholism due to their increased exposure to alcohol. Evolution has allowed higher levels of alcohol dehydrogenase in their bodies. CYP2EI regulates how fast people get drunk. People with the gene (10-20% of the Canadian population) are likely to get drunk after only a few drinks – this low tolerance appears to protect them from becoming alcoholics.
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.
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^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 Biochemistry110 (4): 559–65. PMID1778977.
^Caetano and Clark, 1998; Fenna and Mix,1971; Luczak et al,2001;Mail et al., 2002; Yin et al., 1988
Smith G, Stubbins MJ, Harries LW, Wolf CR (Dec 1998). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica; The Fate of Foreign Compounds in Biological Systems28 (12): 1129–65. doi:10.1080/004982598238868. PMID9890157.
Kessova I, Cederbaum AI (Sep 2003). "CYP2E1: biochemistry, toxicology, regulation and function in ethanol-induced liver injury". Current Molecular Medicine3 (6): 509–18. doi:10.2174/1566524033479609. PMID14527082.
Webb A, Lind PA, Kalmijn J, Feiler HS, Smith TL, Schuckit MA et al. (Jan 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 Research35 (1): 10–18. doi:10.1111/j.1530-0277.2010.01317.x. PMID20958328.