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		<summary type="html">&lt;p&gt;Add 2 books for verifiability (20260417sim)) #IABot (v2.0.9.5) (&lt;a href=&quot;/index.php?title=User:GreenC_bot&amp;amp;action=edit&amp;amp;redlink=1&quot; class=&quot;new&quot; title=&quot;User:GreenC bot（页面不存在）&quot;&gt;GreenC bot&lt;/a&gt;&lt;/p&gt;
&lt;p&gt;&lt;b&gt;新页面&lt;/b&gt;&lt;/p&gt;&lt;div&gt;{{Infobox_gene}}&lt;br /&gt;
&amp;#039;&amp;#039;&amp;#039;细胞色素P450 2E1&amp;#039;&amp;#039;&amp;#039; （缩写为 &amp;#039;&amp;#039;&amp;#039;CYP2E1&amp;#039;&amp;#039;&amp;#039;，{{EC number|1.14.13.n7}} 化学式为：C&amp;lt;sub&amp;gt;2636&amp;lt;/sub&amp;gt;H&amp;lt;sub&amp;gt;4053&amp;lt;/sub&amp;gt;O&amp;lt;sub&amp;gt;709&amp;lt;/sub&amp;gt;N&amp;lt;sub&amp;gt;691&amp;lt;/sub&amp;gt;S&amp;lt;sub&amp;gt;20&amp;lt;/sub&amp;gt;Fe&amp;lt;ref&amp;gt;{{Cite web |title=細胞色素P450 2E1 {{!}} Expasy - ProtParam(注，计算结果包含了血红素辅基) |url=https://web.expasy.org/cgi-bin/protparam/protparam_bis.cgi?P05181@1-493@ |access-date=2026-01-03 |website=web.expasy.org}}&amp;lt;/ref&amp;gt;）。它是[[细胞色素P450]]混合功能氧化酶系统的一员，该系统参与体内[[外源物质]]的代谢。这类酶可细分为多个子类别，包括CYP1、CYP2和CYP3，作为一个群体，它们主要负责哺乳动物体内外来化合物的分解。&amp;lt;ref name=&amp;quot;Lewis_2003&amp;quot;&amp;gt;{{cite journal | vauthors = Lewis DF, Lake BG, Bird MG, Loizou GD, Dickins M, Goldfarb PS | title = Homology modelling of human CYP2E1 based on the CYP2C5 crystal structure: investigation of enzyme-substrate and enzyme-inhibitor interactions | journal = Toxicology in Vitro | volume = 17 | issue = 1 | pages = 93–105 | date = Feb 2003 | pmid = 12537967 | doi=10.1016/s0887-2333(02)00098-x | bibcode = 2003ToxVi..17...93L }}&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
虽然CYP2E1本身进行的这类反应相对较少（约占已知P450介导的药物氧化反应的4%），但它和相关酶[[CYP1A2]]及[[CYP3A4]]负责分解进入体内的许多有毒环境化学物质和致癌物，此外还承担基本的代谢反应，如脂肪酸氧化。&amp;lt;ref name=&amp;quot;Rendic_1997&amp;quot;&amp;gt;{{cite journal | vauthors = Rendic S, Di Carlo FJ | title = Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors | journal = Drug Metabolism Reviews | volume = 29 | issue = 1–2 | pages = 413–580 | pmid = 9187528 | year = 1997 | doi=10.3109/03602539709037591}}&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
CYP2E1蛋白定位于内质网，并可被乙醇、糖尿病状态和饥饿所诱导。该酶代谢多种内源性底物，如乙醇、丙酮和乙醛，以及外源性底物，包括苯、四氯化碳、乙二醇和亚硝胺（香烟烟雾中的前诱变剂）。由于其底物众多，该酶可能参与多种不同的过程，如糖异生、肝硬化、糖尿病和癌症。&amp;lt;ref name=&amp;quot;refseq&amp;quot;&amp;gt;{{NCBI RefSeq|title=CYP2E1 cytochrome P450 family 2 subfamily E member 1 [ Homo sapiens (human) ]|url=https://www.ncbi.nlm.nih.gov/gene/1551}}&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
== 功能 ==&lt;br /&gt;
CYP2E1是一种[[膜蛋白]]，在肝脏中高水平表达，占总肝脏细胞色素P450 mRNA的近50%&amp;lt;ref name=&amp;quot;Bièche_2007&amp;quot;&amp;gt;{{cite journal | vauthors = Bièche I, Narjoz C, Asselah T, Vacher S, Marcellin P, Lidereau R, Beaune P, de Waziers I | title = Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues | journal = Pharmacogenetics and Genomics | volume = 17 | issue = 9 | pages = 731–42 | date = Sep 2007 | pmid = 17700362 | doi = 10.1097/FPC.0b013e32810f2e58 | s2cid = 23317899 }}&amp;lt;/ref&amp;gt;和肝脏细胞色素P450蛋白的7%。&amp;lt;ref name=&amp;quot;Shimada_1994&amp;quot;&amp;gt;{{cite journal | vauthors = Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP | title = Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 270 | issue = 1 | pages = 414–23 | date = Jul 1994 | doi = 10.1016/S0022-3565(25)22379-5 | pmid = 8035341 }}&amp;lt;/ref&amp;gt;因此，肝脏是大多数药物通过CYP2E1直接失活或通过促进[[排泄]]从体内清除的主要场所。&lt;br /&gt;
&lt;br /&gt;
CYP2E1酶主要代谢小型极性分子，包括有毒实验室化学品，如[[二甲基甲酰胺]]、[[苯胺]]和[[卤代烃]]&amp;#039;&amp;#039;（见下表）&amp;#039;&amp;#039;。虽然这些氧化反应通常对身体有益，但某些[[致癌物]]和[[毒素]]会被CYP2E1[[生物活化]]，这意味着该酶与某些类别药物引起的[[肝毒性]]的发生有关&amp;#039;&amp;#039;（见下文疾病相关性部分）。&amp;#039;&amp;#039;&lt;br /&gt;
&lt;br /&gt;
CYP2E1还在几个重要的代谢反应中发挥作用，包括在人体内将乙醇转化为[[乙醛]]和进一步转化为[[乙酸]]，&amp;lt;ref name=&amp;quot;pmid1778977&amp;quot;&amp;gt;{{cite journal | vauthors = Hayashi S, Watanabe J, Kawajiri K | title = Genetic polymorphisms in the 5&amp;#039;-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene | journal = Journal of Biochemistry | volume = 110 | issue = 4 | pages = 559–65 | date = Oct 1991 | pmid = 1778977 | doi =  10.1093/oxfordjournals.jbchem.a123619}}&amp;lt;/ref&amp;gt;在此过程中它与[[乙醇脱氢酶]]和[[乙醛脱氢酶]]协同工作。在[[乙酰辅酶A]]转化为葡萄糖的序列中，CYP2E1将[[丙酮]]通过[[羟基丙酮]]转化为[[丙二醇]]和[[甲基乙二醛]]，它们是[[丙酮酸]]、[[乙酸]]和[[乳酸]]的前体。&amp;lt;ref name=&amp;quot;Glew2010&amp;quot;&amp;gt;{{cite web|url=http://www.bioline.org.br/request?np10002|author=Glew, Robert H|title=You Can Get There From Here: Acetone, Anionic Ketones and Even-Carbon Fatty Acids can Provide Substrates for Gluconeogenesis|access-date=March 8, 2014|archive-url=https://web.archive.org/web/20130926031021/http://www.bioline.org.br/request?np10002|archive-date=September 26, 2013|url-status=dead}}&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;{{cite journal | vauthors = Miller ON, Bazzano G | title = Propanediol metabolism and its relation to lactic acid metabolism | journal = Annals of the New York Academy of Sciences | volume = 119 | issue = 3 | pages = 957–73 | date = Jul 1965 | pmid = 4285478 | doi = 10.1111/j.1749-6632.1965.tb47455.x | bibcode = 1965NYASA.119..957M | s2cid = 37769342 }}&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;{{cite journal | vauthors = Ruddick JA | year = 1972 | title = Toxicology, metabolism, and biochemistry of 1,2-propanediol | journal = Toxicol Appl Pharmacol | volume = 21 | issue = 1 | pages = 102–111 | doi = 10.1016/0041-008X(72)90032-4 | pmid = 4553872 | bibcode = 1972ToxAP..21..102R }}&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
CYP2E1还负责代谢内源性脂肪酸，例如对[[花生四烯酸]]等脂肪酸进行ω-1羟基化，使其参与重要的信号通路，这可能将其与糖尿病和肥胖联系起来。&amp;lt;ref name=&amp;quot;Porubsky_2008&amp;quot;&amp;gt;{{cite journal | vauthors = Porubsky PR, Meneely KM, Scott EE | title = Structures of human cytochrome P-450 2E1. Insights into the binding of inhibitors and both small molecular weight and fatty acid substrates | url = https://archive.org/details/sim_journal-of-biological-chemistry_2008-11-28_283_48/page/33698 | journal = The Journal of Biological Chemistry | volume = 283 | issue = 48 | pages = 33698–707 | date = Nov 2008 | pmid = 18818195 | pmc = 2586265 | doi = 10.1074/jbc.M805999200 | doi-access = free }}&amp;lt;/ref&amp;gt;因此，它作为单加氧酶将[[花生四烯酸]]代谢为19-羟基二十碳四烯酸（19-HETE）（参见[[20-羟基二十碳四烯酸]]）。然而，它也通过[[环氧化酶]]活性将[[二十二碳六烯酸]]代谢为[[环氧化物]]，主要是19&amp;#039;&amp;#039;R&amp;#039;&amp;#039;,20&amp;#039;&amp;#039;S&amp;#039;&amp;#039;-环氧二十碳五烯酸和19&amp;#039;&amp;#039;S&amp;#039;&amp;#039;,20&amp;#039;&amp;#039;R&amp;#039;&amp;#039;-环氧二十碳五烯酸异构体（称为19,20-EDP），并将[[二十碳五烯酸]]代谢为环氧化物，主要是17&amp;#039;&amp;#039;R&amp;#039;&amp;#039;,18&amp;#039;&amp;#039;S&amp;#039;&amp;#039;-环氧二十碳四烯酸和17&amp;#039;&amp;#039;S&amp;#039;&amp;#039;,18&amp;#039;&amp;#039;R&amp;#039;&amp;#039;-环氧二十碳四烯酸异构体（称为17,18-EEQ）。&amp;lt;ref&amp;gt;{{cite journal | vauthors = Westphal C, Konkel A, Schunck WH | title = CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease? | journal = Prostaglandins &amp;amp; Other Lipid Mediators | volume = 96 | issue = 1–4 | pages = 99–108 | date = Nov 2011 | pmid = 21945326 | doi = 10.1016/j.prostaglandins.2011.09.001 | doi-access = free }}&amp;lt;/ref&amp;gt;19-HETE是20-HETE的抑制剂，20-HETE是一种具有广泛活性的信号分子，例如，它能收缩[[小动脉]]、升高血压、促进[[炎症]]反应并刺激多种肿瘤细胞的生长；然而，19-HETE在体内抑制[[20-HETE]]的能力和重要性尚未得到证实。EDP（[[环氧二十二碳五烯酸]]）和EEQ（[[环氧二十碳四烯酸]]）代谢物具有广泛活性。在各种动物模型以及动物和人体组织的体外研究中，它们能降低高血压和痛觉；抑制炎症；抑制[[血管生成]]、内皮细胞迁移和内皮细胞增殖；并抑制人乳腺癌和前列腺癌细胞系的生长和转移。&amp;lt;ref name=&amp;quot;ReferenceA&amp;quot;&amp;gt;{{cite journal | vauthors = Fleming I | title = The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease | journal = Pharmacological Reviews | volume = 66 | issue = 4 | pages = 1106–40 | date = Oct 2014 | pmid = 25244930 | doi = 10.1124/pr.113.007781 | s2cid = 39465144 | doi-access =  }}&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;{{cite journal | vauthors = Zhang G, Kodani S, Hammock BD | title = Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer | journal = Progress in Lipid Research | volume = 53 | pages = 108–23 | date = Jan 2014 | pmid = 24345640 | pmc = 3914417 | doi = 10.1016/j.plipres.2013.11.003 }}&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;{{cite journal | vauthors = He J, Wang C, Zhu Y, Ai D | title = Soluble epoxide hydrolase: A potential target for metabolic diseases | journal = Journal of Diabetes | volume = 8 | issue = 3 | pages = 305–13 | date = Dec 2015 | pmid = 26621325 | doi = 10.1111/1753-0407.12358 | doi-access = free }}&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;pmid25240260&amp;quot;&amp;gt;{{cite journal | vauthors = Wagner K, Vito S, Inceoglu B, Hammock BD | title = The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling | journal = Prostaglandins &amp;amp; Other Lipid Mediators | volume = 113–115 | pages = 2–12 | date = Oct 2014 | pmid = 25240260 | pmc = 4254344 | doi = 10.1016/j.prostaglandins.2014.09.001 }}&amp;lt;/ref&amp;gt;有人认为，EDP和EEQ代谢物在人体内的功能与其在动物模型中的作用相同，并且作为[[omega-3脂肪酸]]（二十二碳六烯酸和二十碳五烯酸）的产物，EDP和EEQ代谢物有助于实现膳食omega-3脂肪酸的许多有益效果。&amp;lt;ref name=&amp;quot;ReferenceA&amp;quot;/&amp;gt;&amp;lt;ref name=&amp;quot;pmid25240260&amp;quot;/&amp;gt;&amp;lt;ref&amp;gt;{{cite journal | vauthors = Fischer R, Konkel A, Mehling H, Blossey K, Gapelyuk A, Wessel N, von Schacky C, Dechend R, Muller DN, Rothe M, Luft FC, Weylandt K, Schunck WH | title = Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway | journal = Journal of Lipid Research | volume = 55 | issue = 6 | pages = 1150–1164 | date = Mar 2014 | pmid = 24634501 | pmc = 4031946 | doi = 10.1194/jlr.M047357  |doi-access=free }}&amp;lt;/ref&amp;gt;EDP和EEQ代谢物是短命的，在形成后几秒或几分钟内就会被[[环氧水解酶]]（特别是[[可溶性环氧水解酶]]）失活，因此仅在局部起作用。CYP2E1不被认为是形成上述环氧化物的主要贡献者，&amp;lt;ref name=&amp;quot;pmid25240260&amp;quot;/&amp;gt;但可能在特定组织中局部发挥作用。&lt;br /&gt;
&lt;br /&gt;
=== 底物 ===&lt;br /&gt;
以下是选定的CYP2E1 [[酶底物|底物]]列表。如果列出了某类药物，该类别中可能存在例外情况。&lt;br /&gt;
{| class=&amp;quot;wikitable sortable&amp;quot;&lt;br /&gt;
|+&amp;#039;&amp;#039;&amp;#039;CYP2E1的选定底物&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
|-&lt;br /&gt;
! 底物&lt;br /&gt;
|- style=&amp;quot;vertical-align: top;&amp;quot;&lt;br /&gt;
&lt;br /&gt;
|&lt;br /&gt;
&lt;br /&gt;
· [[麻醉药]]：&lt;br /&gt;
  ** [[氟烷]]&amp;lt;ref name=&amp;quot;FASS&amp;quot;&amp;gt;[http://www.fass.se/LIF/produktfakta/fakta_lakare_artikel.jsp?articleID=18352 Swedish environmental classification of pharmaceuticals] {{Webarchive|url=https://web.archive.org/web/20020611044953/http://www.fass.se/LIF/produktfakta/fakta_lakare_artikel.jsp?articleID=18352 |date=2002-06-11 }} Facts for prescribers (Fakta för förskrivare)&amp;lt;/ref&amp;gt;&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;&lt;br /&gt;
  ** [[恩氟烷]]&amp;lt;ref name=&amp;quot;FASS&amp;quot; /&amp;gt;&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;&lt;br /&gt;
  ** [[异氟烷]]&amp;lt;ref name=&amp;quot;Flockhart&amp;quot;&amp;gt;{{cite web |author=Flockhart DA |title=Drug Interactions: Cytochrome P&amp;lt;sub&amp;gt;450&amp;lt;/sub&amp;gt; Drug Interaction Table |publisher=[[Indiana University School of Medicine]] |year=2007 |url=http://medicine.iupui.edu/flockhart/table.htm |access-date=2011-07-10 |archive-date=2007-10-10 |archive-url=https://web.archive.org/web/20071010053126/http://medicine.iupui.edu/flockhart/table.htm |url-status=dead }} Retrieved on July 2011&amp;lt;/ref&amp;gt;&lt;br /&gt;
  ** [[甲氧氟烷]]&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;&lt;br /&gt;
  ** [[七氟烷]]&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;&lt;br /&gt;
· [[扑热息痛]]&amp;lt;ref name=&amp;quot;FASS&amp;quot; /&amp;gt;（[[对乙酰氨基酚]]）- 用作[[镇痛药]]、[[解热药]] - 由CYP2E1进行[[毒性激活]]&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;&lt;br /&gt;
· [[乙醇]]&amp;lt;ref name=&amp;quot;FASS&amp;quot; /&amp;gt;&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;（[[精神活性物质]]）&lt;br /&gt;
· 工业潜在有毒物质&lt;br /&gt;
  ** [[苯胺]]&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;&lt;br /&gt;
  ** [[苯]]&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;&lt;br /&gt;
  ** [[二甲基甲酰胺]]&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;&lt;br /&gt;
· [[茶碱]]&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;（[[兴奋剂]]，[[咖啡因]]的活性[[代谢物]]）&lt;br /&gt;
· [[氯唑沙宗]]&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;（[[肌肉松弛剂]]）&lt;br /&gt;
· [[佐匹克隆]]&amp;lt;ref name = &amp;quot;Assessment&amp;quot;&amp;gt;{{cite web|title=Assessment of Zopiclone|url=https://www.who.int/medicines/areas/quality_safety/4.6ZopicloneCritReview.pdf|website=World Health Organization. Essential Medicines and Health Products|publisher=World Health Organization|year=2006|access-date=5 December 2015|page=9 (Section 5. Pharmacokinetics)|archive-date=27 September 2007|archive-url=https://web.archive.org/web/20070927120921/https://www.who.int/medicines/areas/quality_safety/4.6ZopicloneCritReview.pdf|url-status=live}}&amp;lt;/ref&amp;gt;和[[艾司佐匹克隆]]（[[镇静剂]]/[[安眠药]]）&lt;br /&gt;
· [[维拉帕米]]（次要/中度敏感底物&amp;lt;ref name=&amp;quot;UpToDate&amp;quot;&amp;gt;{{cite web | title=Verapamil: Drug information. Lexicomp | website=UpToDate | url=https://www.uptodate.com/contents/verapamil-drug-information | access-date=2019-01-13 | archive-date=2019-01-13 | archive-url=https://web.archive.org/web/20190113232158/https://www.uptodate.com/contents/verapamil-drug-information | url-status=live }}&amp;lt;/ref&amp;gt;）&lt;br /&gt;
  |-&lt;br /&gt;
  |}&lt;br /&gt;
&lt;br /&gt;
== 结构 ==&lt;br /&gt;
CYP2E1展现出与其他人类膜结合[[细胞色素P450]]酶常见的结构基序，由12个主要α-螺旋和4个β-折叠组成，两者之间散布着短的中间螺旋。&amp;lt;ref name=&amp;quot;Porubsky_2008&amp;quot;/&amp;gt;与该类别的其他[[酶]]一样，CYP2E1的[[活性位点]]包含一个由[[血红素]]中心结合的[[铁]]原子，该中心介导了底物[[氧化还原|氧化]]所需的[[电子传递]]步骤。CYP2E1的活性位点是观察到的所有人类P450酶中最小的，其容量小部分归因于在第115位引入了异亮氨酸。该残基的侧链突出于血红素中心之上，与在该位置具有较小体积[[氨基酸|残基]]的相关酶相比，限制了活性位点的容积。&amp;lt;ref name=&amp;quot;Porubsky_2008&amp;quot;/&amp;gt;同样突出到活性位点中的T&amp;lt;sup&amp;gt;303&amp;lt;/sup&amp;gt;对于底物在反应性铁中心上方的定位特别重要，因此被许多细胞色素P450酶高度保守。&amp;lt;ref name=&amp;quot;Porubsky_2008&amp;quot;/&amp;gt;其羟基的位置非常适合向底物上的潜在受体提供[[氢键]]，其甲基基团也被认为与脂肪酸在活性位点内的定位有关。&amp;lt;ref&amp;gt;{{cite journal | vauthors = Fukuda T, Imai Y, Komori M, Nakamura M, Kusunose E, Satouchi K, Kusunose M | title = Replacement of Thr-303 of P450 2E1 with serine modifies the regioselectivity of its fatty acid hydroxylase activity | journal = Journal of Biochemistry | volume = 113 | issue = 1 | pages = 7–12 | date = Jan 1993 | doi = 10.1093/oxfordjournals.jbchem.a124006 | pmid = 8454577 }}&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;{{cite journal | vauthors = Fukuda T, Imai Y, Komori M, Nakamura M, Kusunose E, Satouchi K, Kusunose M | title = Different mechanisms of regioselection of fatty acid hydroxylation by laurate (omega-1)-hydroxylating P450s, P450 2C2 and P450 2E1 | journal = Journal of Biochemistry | volume = 115 | issue = 2 | pages = 338–44 | date = Feb 1994 | doi = 10.1093/oxfordjournals.jbchem.a124339 | pmid = 8206883 }}&amp;lt;/ref&amp;gt;活性位点附近的一些残基，包括L&amp;lt;sup&amp;gt;368&amp;lt;/sup&amp;gt;，有助于形成一个狭窄的疏水通道，该通道可能对于确定酶对小分子的特异性以及脂肪酸的ω-1羟基化也很重要。&amp;lt;ref name=&amp;quot;Porubsky_2008&amp;quot;/&amp;gt; [[File:CYP2E1 Active site.png|centre|thumb|302x302px|CYP2E1活性位点中的选定残基。使用结合抑制剂4-甲基吡唑的3E4E结构创建。]]&lt;br /&gt;
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== 调控 ==&lt;br /&gt;
&lt;br /&gt;
=== 遗传调控 ===&lt;br /&gt;
在人类中，CYP2E1酶由&amp;#039;&amp;#039;CYP2E1&amp;#039;&amp;#039; [[基因]]编码。&amp;lt;ref name=&amp;quot;pmid8307581&amp;quot;&amp;gt;{{cite journal | vauthors = Kölble K | title = Regional mapping of short tandem repeats on human chromosome 10: cytochrome P450 gene CYP2E, D10S196, D10S220, and D10S225 | journal = Genomics | volume = 18 | issue = 3 | pages = 702–4 | date = Dec 1993 | pmid = 8307581 | doi = 10.1016/S0888-7543(05)80378-7 }}&amp;lt;/ref&amp;gt;该酶已在胎肝中被发现，被认为是主要的乙醇代谢酶，并可能与乙醇介导的[[致畸作用]]有关。&amp;lt;ref&amp;gt;{{cite journal | vauthors = Raucy JL, Schultz ED, Wester MR, Arora S, Johnston DE, Omdahl JL, Carpenter SP | title = Human lymphocyte cytochrome P450 2E1, a putative marker for alcohol-mediated changes in hepatic chlorzoxazone activity | journal = Drug Metabolism and Disposition | volume = 25 | issue = 12 | pages = 1429–35 | date = Dec 1997 | pmid = 9394034 }}&amp;lt;/ref&amp;gt;在大鼠中，出生后一天内，肝脏CYP2E1基因在转录水平被激活。&lt;br /&gt;
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CYP2E1的表达易于诱导，并且可在其多种底物存在时发生，包括[[乙醇]]、&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;[[异烟肼]]、&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;[[烟草]]、&amp;lt;ref&amp;gt;{{cite journal | vauthors = Desai HD, Seabolt J, Jann MW | title = Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective | journal = CNS Drugs | volume = 15 | issue = 6 | pages = 469–94 | year = 2001 | pmid = 11524025 | doi = 10.2165/00023210-200115060-00005 | s2cid = 13197188 }}&amp;lt;/ref&amp;gt;[[异丙醇]]、&amp;lt;ref name=&amp;quot;Rendic_1997&amp;quot;/&amp;gt;[[苯]]、&amp;lt;ref name=&amp;quot;Rendic_1997&amp;quot;/&amp;gt;[[甲苯]]、&amp;lt;ref name=&amp;quot;Rendic_1997&amp;quot;/&amp;gt;和[[丙酮]]。&amp;lt;ref name=&amp;quot;Rendic_1997&amp;quot;/&amp;gt;具体就乙醇而言，似乎存在两个诱导阶段：在低水平乙醇时，通过翻译后机制增加蛋白质稳定性；在高水平乙醇时，则额外进行转录诱导。&amp;lt;ref name=&amp;quot;pmid10397283&amp;quot;&amp;gt;{{cite journal | vauthors = Lieber CS | title = Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968-1998)--a review | journal = Alcoholism: Clinical and Experimental Research | volume = 23 | issue = 6 | pages = 991–1007 | date = Jun 1999 | pmid = 10397283 | doi = 10.1111/j.1530-0277.1999.tb04217.x }}&amp;lt;/ref&amp;gt;&lt;br /&gt;
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=== 化学调控 ===&lt;br /&gt;
CYP2E1被多种小分子抑制，其中许多以[[竞争性抑制|竞争性]]方式起作用。两种这样的抑制剂，[[吲唑]]和[[4-甲基吡唑]]，与活性位点的铁原子配位，并于2008年与重组人CYP2E1共结晶，首次得到了该酶的真实晶体结构。&amp;lt;ref name=&amp;quot;Porubsky_2008&amp;quot;/&amp;gt;其他抑制剂包括[[二乙基二硫代氨基甲酸酯]]&amp;lt;ref name=&amp;quot;FASS&amp;quot; /&amp;gt;（用于[[癌症]]治疗）和[[双硫仑]]&amp;lt;ref name=&amp;quot;Flockhart&amp;quot; /&amp;gt;（用于[[酒精中毒]]治疗）。&lt;br /&gt;
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== 疾病相关性 ==&lt;br /&gt;
CYP2E1在肝脏中高表达，负责清除体内的毒素。&amp;lt;ref name=&amp;quot;Bièche_2007&amp;quot;/&amp;gt;&amp;lt;ref name=&amp;quot;Shimada_1994&amp;quot;/&amp;gt;在此过程中，CYP2E1对多种常见麻醉剂进行[[生物活化]]，包括[[扑热息痛|扑热息痛（对乙酰氨基酚）]]、[[氟烷]]、[[恩氟烷]]和异氟烷。&amp;lt;ref name=&amp;quot;Rendic_1997&amp;quot; /&amp;gt;这些分子被CYP2E1氧化后可能产生有害物质，例如氟烷产生的[[三氟乙酸|三氟乙酰氯]]&amp;lt;ref&amp;gt;{{cite journal | vauthors = Ray DC, Drummond GB | title = Halothane hepatitis | url = https://archive.org/details/sim_british-journal-of-anaesthesia_1991-07_67_1/page/84 | journal = British Journal of Anaesthesia | volume = 67 | issue = 1 | pages = 84–99 | date = Jul 1991 | pmid = 1859766 | doi=10.1093/bja/67.1.84| doi-access = free }}&amp;lt;/ref&amp;gt;或扑热息痛（对乙酰氨基酚）产生的[[NAPQI]]，这是它们在患者中观察到肝毒性的主要原因。&lt;br /&gt;
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CYP2E1和其他细胞色素P450酶在催化不协调时，可能会在其活性位点无意中产生活性氧（ROS），导致潜在的[[脂质过氧化]]以及蛋白质和DNA氧化。&amp;lt;ref name=&amp;quot;Porubsky_2008&amp;quot;/&amp;gt;与其他P450酶相比，CYP2E1特别容易出现这种现象，这表明其表达水平可能对许多疾病状态下观察到的负面生理效应至关重要。&amp;lt;ref name=&amp;quot;Porubsky_2008&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
CYP2E1的表达水平与多种饮食和生理因素相关，例如乙醇摄入、&amp;lt;ref&amp;gt;{{cite journal | vauthors = Nanji AA, Zhao S, Sadrzadeh SM, Dannenberg AJ, Tahan SR, Waxman DJ | title = Markedly enhanced cytochrome P450 2E1 induction and lipid peroxidation is associated with severe liver injury in fish oil-ethanol-fed rats | journal = Alcoholism: Clinical and Experimental Research | volume = 18 | issue = 5 | pages = 1280–5 | date = Oct 1994 | pmid = 7847620 | doi=10.1111/j.1530-0277.1994.tb00119.x}}&amp;lt;/ref&amp;gt;糖尿病、&amp;lt;ref&amp;gt;{{cite journal | vauthors = Koide CL, Collier AC, Berry MJ, Panee J | title = The effect of bamboo extract on hepatic biotransforming enzymes--findings from an obese-diabetic mouse model | journal = Journal of Ethnopharmacology | volume = 133 | issue = 1 | pages = 37–45 | date = Jan 2011 | pmid = 20832461 | pmc = 3471658 | doi = 10.1016/j.jep.2010.08.062 }}&amp;lt;/ref&amp;gt;禁食&amp;lt;ref&amp;gt;{{cite journal | vauthors = Johansson I, Ekström G, Scholte B, Puzycki D, Jörnvall H, Ingelman-Sundberg M | title = Ethanol-, fasting-, and acetone-inducible cytochromes P-450 in rat liver: regulation and characteristics of enzymes belonging to the IIB and IIE gene subfamilies | journal = Biochemistry | volume = 27 | issue = 6 | pages = 1925–34 | date = Mar 1988 | pmid = 3378038 | doi=10.1021/bi00406a019}}&amp;lt;/ref&amp;gt;和肥胖。&amp;lt;ref&amp;gt;{{cite journal | vauthors = Raucy JL, Lasker JM, Kraner JC, Salazar DE, Lieber CS, Corcoran GB | title = Induction of cytochrome P450IIE1 in the obese overfed rat | journal = Molecular Pharmacology | volume = 39 | issue = 3 | pages = 275–80 | date = Mar 1991 | doi = 10.1016/S0026-895X(25)10989-9 | pmid = 2005876 }}&amp;lt;/ref&amp;gt;细胞内酶的水平似乎可能由分子伴侣[[Hsp90|HSP90]]控制，HSP90与CYP2E1结合后，允许其转运至[[蛋白酶体]]进行降解。乙醇和其他底物可能破坏这种结合，从而导致在其存在下观察到更高的表达水平。&amp;lt;ref&amp;gt;{{cite journal | vauthors = Kitam VO, Maksymchuk OV, Chashchyn MO | title = The possible mechanisms of CYP2E1 interactions with HSP90 and the influence of ethanol on them | language = en | journal = BMC Structural Biology | volume = 12 | issue = 1 | pages = 33 | date = 2012-12-17 | pmid = 23241420 | pmc = 3544703 | doi = 10.1186/1472-6807-12-33 | doi-access = free }}&amp;lt;/ref&amp;gt;因此，伴随这些健康状况而增加的CYP2E1表达，可能通过增加体内ROS的产生速率而促进其[[发病机制]]。&amp;lt;ref name=&amp;quot;Porubsky_2008&amp;quot;/&amp;gt;&lt;br /&gt;
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根据Y Hu等人1995年发表的一项研究，在大鼠中的研究表明，仅禁食就可使CYP2E1水平升高8至9倍，而在禁食并连续3天摄入大量乙醇的大鼠中，酶水平增加了20倍，总催化能力增加了16倍。饥饿似乎上调肝细胞中CYP2E1 mRNA的产生，而酒精似乎在翻译后稳定酶本身，从而保护其免受正常细胞蛋白水解过程的降解，两者产生了独立的协同效应。&lt;br /&gt;
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==应用==&lt;br /&gt;
通过基因工程改造，使树木过表达兔CYP2E1酶。这些[[转基因]]树木已被用于去除地下水中的污染物，这一过程称为[[植物修复]]。&amp;lt;ref name=&amp;quot;pmid17940038&amp;quot;&amp;gt;{{cite journal | vauthors = 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 | title = Enhanced phytoremediation of volatile environmental pollutants with transgenic trees | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 43 | pages = 16816–21 | date = Oct 2007 | pmid = 17940038 | pmc = 2040402 | doi = 10.1073/pnas.0703276104 | bibcode = 2007PNAS..10416816D | doi-access = free }}&amp;lt;/ref&amp;gt;&lt;br /&gt;
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== 参见 ==&lt;br /&gt;
&lt;br /&gt;
· [[细胞色素]]&lt;br /&gt;
· [[代谢]]&lt;br /&gt;
· [[细胞色素P450调节剂列表]]&lt;br /&gt;
&lt;br /&gt;
== 参考文献 ==&lt;br /&gt;
{{Reflist|33em}}&lt;br /&gt;
&lt;br /&gt;
== 进一步阅读 ==&lt;br /&gt;
{{Refbegin|33em}}&lt;br /&gt;
&lt;br /&gt;
· {{cite journal | vauthors = Smith G, Stubbins MJ, Harries LW, Wolf CR | title = Molecular genetics of the human cytochrome P450 monooxygenase superfamily | journal = Xenobiotica | volume = 28 | issue = 12 | pages = 1129–65 | date = Dec 1998 | pmid = 9890157 | doi = 10.1080/004982598238868 }}&lt;br /&gt;
· {{cite journal | vauthors = Kessova I, Cederbaum AI | title = CYP2E1: biochemistry, toxicology, regulation and function in ethanol-induced liver injury | journal = Current Molecular Medicine | volume = 3 | issue = 6 | pages = 509–18 | date = Sep 2003 | pmid = 14527082 | doi = 10.2174/1566524033479609 }}&lt;br /&gt;
· {{cite journal | vauthors = Webb A, Lind PA, Kalmijn J, Feiler HS, Smith TL, Schuckit MA, Wilhelmsen K | title = The investigation into CYP2E1 in relation to the level of response to alcohol through a combination of linkage and association analysis | journal = Alcoholism: Clinical and Experimental Research | volume = 35 | issue = 1 | pages = 10–8 | date = Jan 2011 | pmid = 20958328 | doi = 10.1111/j.1530-0277.2010.01317.x | pmc=3005010}}&lt;br /&gt;
  {{Refend}}&lt;br /&gt;
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==外部链接==&lt;br /&gt;
&lt;br /&gt;
· {{UCSC gene info|CYP2E1}}&lt;br /&gt;
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{{Cytochrome P450}}&lt;br /&gt;
{{Dioxygenases}}&lt;br /&gt;
{{Enzymes}}&lt;br /&gt;
{{Portal bar|Biology|border=no}}&lt;br /&gt;
{{Authority control}}&lt;br /&gt;
&lt;br /&gt;
[[Category:Cytochrome P450|2]]&lt;br /&gt;
[[Category:EC 1.14.13]]&lt;/div&gt;</summary>
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