CYP2E1

Last updated
CYP2E1
Protein CYP2E1 PDB 3E4E.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CYP2E1 , CPE1, CYP2E, P450-J, P450C2E, cytochrome P450 family 2 subfamily E member 1
External IDs OMIM: 124040; MGI: 88607; HomoloGene: 68089; GeneCards: CYP2E1; OMA:CYP2E1 - orthologs
EC number 1.14.13.n7
Orthologs
SpeciesHumanMouse
Entrez

1571

13106

Ensembl

ENSG00000130649

ENSMUSG00000025479

UniProt

P05181

Q05421

RefSeq (mRNA)

NM_000773

NM_021282

RefSeq (protein)

NP_000764

NP_067257

Location (UCSC) Chr 10: 133.52 – 133.56 Mb Chr 7: 140.34 – 140.35 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Cytochrome P450 2E1 (abbreviated CYP2E1, EC 1.14.13.n7) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals. [5]

Contents

While CYP2E1 itself carries out a relatively low number of these reactions (~4% of known P450-mediated drug oxidations), it and related enzymes CYP1A2 and CYP3A4 are responsible for the breakdown of many toxic environmental chemicals and carcinogens that enter the body, in addition to basic metabolic reactions such as fatty acid oxidations. [6]

CYP2E1 protein localizes to the endoplasmic reticulum and is induced by ethanol, the diabetic state, and starvation. The enzyme metabolizes both endogenous substrates, such as ethanol, acetone, and acetal, as well as exogenous substrates including benzene, carbon tetrachloride, ethylene glycol, and nitrosamines which are premutagens found in cigarette smoke. Due to its many substrates, this enzyme may be involved in such varied processes as gluconeogenesis, hepatic cirrhosis, diabetes, and cancer. [7]

Function

CYP2E1 is a membrane protein expressed in high levels in the liver, where it composes nearly 50% of the total hepatic cytochrome P450 mRNA [8] and 7% of the hepatic cytochrome P450 protein. [9] The liver is therefore where most drugs undergo deactivation by CYP2E1, either directly or by facilitated excretion from the body.

CYP2E1 enzyme metabolizes mostly small, polar molecules, including toxic laboratory chemicals such as dimethylformamide, aniline, and halogenated hydrocarbons (see table below). While these oxidations are often of benefit to the body, certain carcinogens and toxins are bioactivated by CYP2E1, implicating the enzyme in the onset of hepatotoxicity caused by certain classes of drugs (see disease relevance section below).

CYP2E1 also plays a role in several important metabolic reactions, including the conversion of ethanol to acetaldehyde and to acetate in humans, [10] where it works alongside alcohol dehydrogenase and aldehyde dehydrogenase. In the conversion sequence of acetyl-CoA to glucose, CYP2E1 transforms acetone via hydroxyacetone (acetol) into propylene glycol and methylglyoxal, the precursors of pyruvate, acetate and lactate. [11] [12] [13]

CYP2E1 also carries out the metabolism of endogenous fatty acids such as the ω-1 hydroxylation of fatty acids such as arachidonic acid, involving it in important signaling pathways that may link it to diabetes and obesity. [14] Thus, it acts as a monooxygenase to metabolize arachidonic acid to 19-hydroxyeicosatetraenoic acid (19-HETE) (see 20-Hydroxyeicosatetraenoic acid). However, it also acts as an epoxygenase activity to metabolize docosahexaenoic acid to epoxides, primarily 19R,20S-epoxyeicosapentaenoic acid and 19S,20R-epoxyeicosapentaenoic acid isomers (termed 19,20-EDP) and eicosapentaenoic acid to epoxides, primarily 17R,18S-eicosatetraenoic acid and 17S,18R-eicosatetraenoic acid isomers (termed 17,18-EEQ). [15] 19-HETE is an inhibitor of 20-HETE, a broadly active signaling molecule, e.g. it constricts arterioles, elevates blood pressure, promotes inflammation responses, and stimulates the growth of various types of tumor cells; however the in vivo ability and significance of 19-HETE in inhibiting 20-HETE has not been demonstrated. The EDP (epoxydocosapentaenoic acid) and EEQ (epoxyeicosatetraenoic acid) metabolites have a broad range of activities. In various animal models and in vitro studies on animal and human tissues, they decrease hypertension and pain perception; suppress inflammation; inhibit angiogenesis, endothelial cell migration and endothelial cell proliferation; and inhibit the growth and metastasis of human breast and prostate cancer cell lines. [16] [17] [18] [19] It is suggested that the EDP and EEQ metabolites function in humans as they do in animal models and that, as products of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid, the EDP and EEQ metabolites contribute to many of the beneficial effects attributed to dietary omega-3 fatty acids. [16] [19] [20] EDP and EEQ metabolites are short-lived, being inactivated within seconds or minutes of formation by epoxide hydrolases, particularly soluble epoxide hydrolase, and therefore act locally. CYP2E1 is not regarded as being a major contributor to forming the cited epoxides [19] but could act locally in certain tissues to do so.

Substrates

Following is a table of selected substrates of CYP2E1. Where classes of agents are listed, there may be exceptions within the class.

Selected substrates of CYP2E1
Substrates

Structure

CYP2E1 exhibits structural motifs common to other human membrane-bound cytochrome P450 enzymes, and is composed of 12 major α-helices and 4 β-sheets with short intervening helices interspersed between the two. [14] Like other enzymes of this class, the active site of CYP2E1 contains an iron atom bound by a heme center which mediates the electron transfer steps necessary to carry out oxidation of its substrates. The active site of CYP2E1 is the smallest observed in human P450 enzymes, with its small capacity attributed in part to the introduction of an isoleucine at position 115. The side-chain of this residue protrudes out above the heme center, restricting active site volume compared to related enzymes that have less bulky residues at this position. [14] T303, which also protrudes into the active site, is particularly important for substrate positioning above the reactive iron center and is hence highly conserved by many cytochrome P450 enzymes. [14] Its hydroxyl group is well-positioned to donate a hydrogen bond to potential acceptors on the substrate, and its methyl group has also been implicated in the positioning of fatty acids within the active site. [25] , [26] A number of residues proximal to the active site including L368 help make up a constricted, hydrophobic access channel which may also be important for determining the enzyme's specificity towards small molecules and ω-1 hydroxylation of fatty acids. [14]

Selected residues in the active site of CYP2E1. Created using 3E4E (bound to inhibitor 4-methyl pyrazole). CYP2E1 Active site.png
Selected residues in the active site of CYP2E1. Created using 3E4E (bound to inhibitor 4-methyl pyrazole).

Regulation

Genetic regulation

In humans, the CYP2E1 enzyme is encoded by the CYP2E1 gene. [27] The enzyme has been identified in fetal liver, where it is posited to be the predominant ethanol-metabolizing enzyme, and may be connected to ethanol-mediated teratogenesis. [28] In rats, within one day of birth the hepatic CYP2E1 gene is activated transcriptionally.

CYP2E1 expression is easily inducible, and can occur in the presence of a number of its substrates, including ethanol, [22] isoniazid, [22] tobacco, [29] isopropanol, [6] benzene, [6] toluene, [6] and acetone. [6] For ethanol specifically, it seems that there exist two stages of induction, a post-translational mechanism for increased protein stability at low levels of ethanol and an additional transcriptional induction at high levels of ethanol. [30]

Chemical regulation

CYP2E1 is inhibited by a variety of small molecules, many of which act competitively. Two such inhibitors, indazole and 4-methylpyrazole, coordinate with the active site's iron atom and were crystallized with recombinant human CYP2E1 in 2008 to give the first true crystal structures of the enzyme. [14] Other inhibitors include diethyldithiocarbamate [21] (in cancer), and disulfiram [22] (in alcoholism).

Disease relevance

CYP2E1 is expressed in high levels in the liver, where it works to clear toxins from the body. [8] [9] In doing so, CYP2E1 bioactivates a variety of common anesthetics, including paracetamol (acetaminophen), halothane, enflurane, and isoflurane. [6] The oxidation of these molecules by CYP2E1 can produce harmful substances such as trifluoroacetic acid chloride from halothane [31] or NAPQI from paracetamol (acetaminophen) and is a major reason for their observed hepatotoxicity in patients.

CYP2E1 and other cytochrome P450 enzymes can inadvertently produce reactive oxygen species (ROS) in their active site when catalysis is not coordinated correctly, resulting in potential lipid peroxidation as well as protein and DNA oxidation. [14] CYP2E1 is particularly susceptible to this phenomenon compared to other P450 enzymes, suggesting that its expression levels may be important for negative physiological effects observed in a number of disease states. [14]

CYP2E1 expression levels have been correlated with a variety of dietary and physiological factors, such as ethanol consumption, [32] diabetes, [33] fasting, [34] and obesity. [35] It appears that cellular levels of the enzyme may be controlled by the molecular chaperone HSP90, which upon association with CYP2E1 allows for transport to the proteasome and subsequent degradation. Ethanol and other substrates may disrupt this association, leading to the higher expression levels observed in their presence. [36] The increased expression of CYP2E1 accompanying these health conditions may therefore contribute to their pathogenesis by increasing the rate of production of ROS in the body. [14]

According to a 1995 publication by Y Hu et al., a study in rats revealed a 8- to 9-fold elevation of CYP2E1 with fasting alone, compared to a 20-fold increase in enzyme level accompanied by a 16-fold increase in total catalytic capacity in rats who were both fasted and given large quantities of ethanol for 3 consecutive days. Starvation appears to upregulate CYP2E1 mRNA production in liver cells while alcohol seems to stabilize the enzyme itself post-translation and thus protect it from degradation by normal cellular proteolytic processes, giving the two an independent synergistic effect.

Applications

Trees have been genetically engineered to overexpress rabbit CYP2E1 enzyme. These transgenic trees have been used to remove pollutants from groundwater, a process known as phytoremediation. [37]

See also

Related Research Articles

<span class="mw-page-title-main">CYP1A2</span> Enzyme in the human body

Cytochrome P450 1A2, a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.

The epoxyeicosatrienoic acids or EETs are signaling molecules formed within various types of cells by the metabolism of arachidonic acid by a specific subset of cytochrome P450 enzymes termed cytochrome P450 epoxygenases. These nonclassic eicosanoids are generally short-lived, being rapidly converted from epoxides to less active or inactive dihydroxy-eicosatrienoic acids (diHETrEs) by a widely distributed cellular enzyme, soluble epoxide hydrolase (sEH), also termed epoxide hydrolase 2. The EETs consequently function as transiently acting, short-range hormones; that is, they work locally to regulate the function of the cells that produce them or of nearby cells. The EETs have been most studied in animal models where they show the ability to lower blood pressure possibly by a) stimulating arterial vasorelaxation and b) inhibiting the kidney's retention of salts and water to decrease intravascular blood volume. In these models, EETs prevent arterial occlusive diseases such as heart attacks and brain strokes not only by their anti-hypertension action but possibly also by their anti-inflammatory effects on blood vessels, their inhibition of platelet activation and thereby blood clotting, and/or their promotion of pro-fibrinolytic removal of blood clots. With respect to their effects on the heart, the EETs are often termed cardio-protective. Beyond these cardiovascular actions that may prevent various cardiovascular diseases, studies have implicated the EETs in the pathological growth of certain types of cancer and in the physiological and possibly pathological perception of neuropathic pain. While studies to date imply that the EETs, EET-forming epoxygenases, and EET-inactivating sEH can be manipulated to control a wide range of human diseases, clinical studies have yet to prove this. Determination of the role of the EETS in human diseases is made particularly difficult because of the large number of EET-forming epoxygenases, large number of epoxygenase substrates other than arachidonic acid, and the large number of activities, some of which may be pathological or injurious, that the EETs possess.

<span class="mw-page-title-main">CYP2C9</span> Enzyme protein

Cytochrome P450 family 2 subfamily C member 9 is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the CYP2C9 gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme.

<span class="mw-page-title-main">CYP2C19</span> Mammalian protein found in humans

Cytochrome P450 2C19 is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some proton pump inhibitors and antiepileptic drugs. In humans, it is the CYP2C19 gene that encodes the CYP2C19 protein. CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.

<span class="mw-page-title-main">CYP2C8</span> Gene-coded protein involved in metabolism of xenobiotics

Cytochrome P4502C8 (CYP2C8) is a member of the cytochrome P450 mixed-function oxidase system involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-chain polyunsaturated fatty acids, e.g. arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and linoleic acid to their biologically active epoxides.

Omega oxidation (ω-oxidation) is a process of fatty acid metabolism in some species of animals. It is an alternative pathway to beta oxidation that, instead of involving the β carbon, involves the oxidation of the ω carbon. The process is normally a minor catabolic pathway for medium-chain fatty acids, but becomes more important when β oxidation is defective.

<span class="mw-page-title-main">CYP1A1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes.

Ethanol, an alcohol found in nature and in alcoholic drinks, is metabolized through a complex catabolic metabolic pathway. In humans, several enzymes are involved in processing ethanol first into acetaldehyde and further into acetic acid and acetyl-CoA. Once acetyl-CoA is formed, it becomes a substrate for the citric acid cycle ultimately producing cellular energy and releasing water and carbon dioxide. Due to differences in enzyme presence and availability, human adults and fetuses process ethanol through different pathways. Gene variation in these enzymes can lead to variation in catalytic efficiency between individuals. The liver is the major organ that metabolizes ethanol due to its high concentration of these enzymes.

<span class="mw-page-title-main">CYP2J2</span> Gene of the species Homo sapiens

Cytochrome P450 2J2 (CYP2J2) is a protein that in humans is encoded by the CYP2J2 gene. CYP2J2 is a member of the cytochrome P450 superfamily of enzymes. The enzymes are oxygenases which catalyze many reactions involved in the metabolism of drugs and other xenobiotics) as well as in the synthesis of cholesterol, steroids and other lipids.

<span class="mw-page-title-main">CYP2C18</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 2C18 is a protein that in humans is encoded by the CYP2C18 gene.

<span class="mw-page-title-main">CYP4A11</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 4A11 is a protein that in humans is codified by the CYP4A11 gene.

<span class="mw-page-title-main">CYP4F2</span> Enzyme protein in the species Homo sapiens

Cytochrome P450 4F2 is a protein that in humans is encoded by the CYP4F2 gene. This protein is an enzyme, a type of protein that catalyzes chemical reactions inside cells. This specific enzyme is part of the superfamily of cytochrome P450 (CYP) enzymes, and the encoding gene is part of a cluster of cytochrome P450 genes located on chromosome 19.

<span class="mw-page-title-main">CYP4F8</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 4F8 is a protein that in humans is encoded by the CYP4F8 gene.

<span class="mw-page-title-main">CYP4F12</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 4F12 is a protein that in humans is encoded by the CYP4F12 gene.

<span class="mw-page-title-main">CYP4F3</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 4F3, also leukotriene-B(4) omega-hydroxylase 2, is an enzyme that in humans is encoded by the CYP4F3 gene. CYP4F3 encodes two distinct enzymes, CYP4F3A and CYP4F3B, which originate from the alternative splicing of a single pre-mRNA precursor molecule; selection of either isoform is tissue-specific with CYP3F3A being expressed mostly in leukocytes and CYP4F3B mostly in the liver.

Epoxygenases are a set of membrane-bound, heme-containing cytochrome P450 enzymes that metabolize polyunsaturated fatty acids to epoxide products that have a range of biological activities. The most thoroughly studied substrate of the CYP epoxylgenases is arachidonic acid. This polyunsaturated fatty acid is metabolized by cyclooxygenases to various prostaglandin, thromboxane, and prostacyclin metabolites in what has been termed the first pathway of eicosanoid production; it is also metabolized by various lipoxygenases to hydroxyeicosatetraenoic acids and leukotrienes in what has been termed the second pathway of eicosanoid production. The metabolism of arachidonic acid to epoxyeicosatrienoic acids by the CYP epoxygenases has been termed the third pathway of eicosanoid metabolism. Like the first two pathways of eicosanoid production, this third pathway acts as a signaling pathway wherein a set of enzymes metabolize arachidonic acid to a set of products that act as secondary signals to work in activating their parent or nearby cells and thereby orchestrate functional responses. However, none of these three pathways is limited to metabolizing arachidonic acid to eicosanoids. Rather, they also metabolize other polyunsaturated fatty acids to products that are structurally analogous to the eicosanoids but often have different bioactivity profiles. This is particularly true for the CYP epoxygenases which in general act on a broader range of polyunsaturated fatty acids to form a broader range of metabolites than the first and second pathways of eicosanoid production. Furthermore, the latter pathways form metabolites many of which act on cells by binding with and thereby activating specific and well-characterized receptor proteins; no such receptors have been fully characterized for the epoxide metabolites. Finally, there are relatively few metabolite-forming lipoxygenases and cyclooxygenases in the first and second pathways and these oxygenase enzymes share similarity between humans and other mammalian animal models. The third pathway consists of a large number of metabolite-forming CYP epoxygenases and the human epoxygenases have important differences from those of animal models. Partly because of these differences, it has been difficult to define clear roles for the epoxygenase-epoxide pathways in human physiology and pathology.

<span class="mw-page-title-main">CYP4A22</span> Protein-coding gene in the species Homo sapiens

CYP4A22 also known as fatty acid omega-hydroxylase is a protein which in humans is encoded by the CYP4A22 gene.

<span class="mw-page-title-main">Epoxydocosapentaenoic acid</span> Group of chemical compounds

Epoxide docosapentaenoic acids are metabolites of the 22-carbon straight-chain omega-3 fatty acid, docosahexaenoic acid (DHA). Cell types that express certain cytochrome P450 (CYP) epoxygenases metabolize polyunsaturated fatty acids (PUFAs) by converting one of their double bonds to an epoxide. In the best known of these metabolic pathways, cellular CYP epoxygenases metabolize the 20-carbon straight-chain omega-6 fatty acid, arachidonic acid, to epoxyeicosatrienoic acids (EETs); another CYP epoxygenase pathway metabolizes the 20-carbon omega-3 fatty acid, eicosapentaenoic acid (EPA), to epoxyeicosatetraenoic acids (EEQs). CYP epoxygenases similarly convert various other PUFAs to epoxides. These epoxide metabolites have a variety of activities. However, essentially all of them are rapidly converted to their corresponding, but in general far less active, vicinal dihydroxy fatty acids by ubiquitous cellular soluble epoxide hydrolase. Consequently, these epoxides, including EDPs, operate as short-lived signaling agents that regulate the function of their parent or nearby cells. The particular feature of EDPs distinguishing them from EETs is that they derive from omega-3 fatty acids and are suggested to be responsible for some of the beneficial effects attributed to omega-3 fatty acids and omega-3-rich foods such as fish oil.

<span class="mw-page-title-main">Epoxyeicosatetraenoic acid</span> Chemical compound

Epoxyeicosatetraenoic acids are a set of biologically active epoxides that various cell types make by metabolizing the omega 3 fatty acid, eicosapentaenoic acid (EPA), with certain cytochrome P450 epoxygenases. These epoxygenases can metabolize EPA to as many as 10 epoxides that differ in the site and/or stereoisomer of the epoxide formed; however, the formed EEQs, while differing in potency, often have similar bioactivities and are commonly considered together.

In biochemistry, cytochrome P450 enzymes have been identified in all kingdoms of life: animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses. As of 2018, more than 300,000 distinct CYP proteins are known.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000130649 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025479 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Lewis DF, Lake BG, Bird MG, Loizou GD, Dickins M, Goldfarb PS (Feb 2003). "Homology modelling of human CYP2E1 based on the CYP2C5 crystal structure: investigation of enzyme-substrate and enzyme-inhibitor interactions". Toxicology in Vitro. 17 (1): 93–105. doi:10.1016/s0887-2333(02)00098-x. PMID   12537967.
  6. 1 2 3 4 5 6 Rendic S, Di Carlo FJ (1997). "Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors". Drug Metabolism Reviews. 29 (1–2): 413–580. doi:10.3109/03602539709037591. PMID   9187528.
  7. ↑ PD-icon.svg This article incorporates public domain material from "CYP2E1 cytochrome P450 family 2 subfamily E member 1 [ Homo sapiens (human) ]". Reference Sequence collection . National Center for Biotechnology Information.
  8. 1 2 Bièche I, Narjoz C, Asselah T, Vacher S, Marcellin P, Lidereau R, Beaune P, de Waziers I (Sep 2007). "Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues". Pharmacogenetics and Genomics. 17 (9): 731–42. doi:10.1097/FPC.0b013e32810f2e58. PMID   17700362. S2CID   23317899.
  9. 1 2 Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP (Jul 1994). "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". The Journal of Pharmacology and Experimental Therapeutics. 270 (1): 414–23. PMID   8035341.
  10. ↑ 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 Biochemistry. 110 (4): 559–65. doi:10.1093/oxfordjournals.jbchem.a123619. PMID   1778977.
  11. ↑ Glew, Robert H. "You Can Get There From Here: Acetone, Anionic Ketones and Even-Carbon Fatty Acids can Provide Substrates for Gluconeogenesis". Archived from the original on September 26, 2013. Retrieved March 8, 2014.
  12. ↑ Miller ON, Bazzano G (Jul 1965). "Propanediol metabolism and its relation to lactic acid metabolism". Annals of the New York Academy of Sciences. 119 (3): 957–73. Bibcode:1965NYASA.119..957M. doi:10.1111/j.1749-6632.1965.tb47455.x. PMID   4285478. S2CID   37769342.
  13. ↑ Ruddick JA (1972). "Toxicology, metabolism, and biochemistry of 1,2-propanediol". Toxicol Appl Pharmacol. 21 (1): 102–111. doi:10.1016/0041-008X(72)90032-4. PMID   4553872.
  14. 1 2 3 4 5 6 7 8 9 Porubsky PR, Meneely KM, Scott EE (Nov 2008). "Structures of human cytochrome P-450 2E1. Insights into the binding of inhibitors and both small molecular weight and fatty acid substrates". The Journal of Biological Chemistry. 283 (48): 33698–707. doi: 10.1074/jbc.M805999200 . PMC   2586265 . PMID   18818195.
  15. ↑ Westphal C, Konkel A, Schunck WH (Nov 2011). "CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?". Prostaglandins & Other Lipid Mediators. 96 (1–4): 99–108. doi:10.1016/j.prostaglandins.2011.09.001. PMID   21945326.
  16. 1 2 Fleming I (Oct 2014). "The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease". Pharmacological Reviews. 66 (4): 1106–40. doi:10.1124/pr.113.007781. PMID   25244930. S2CID   39465144.
  17. ↑ Zhang G, Kodani S, Hammock BD (Jan 2014). "Stabilized epoxygenated fatty acids regulate inflammation, pain, angiogenesis and cancer". Progress in Lipid Research. 53: 108–23. doi:10.1016/j.plipres.2013.11.003. PMC   3914417 . PMID   24345640.
  18. ↑ He J, Wang C, Zhu Y, Ai D (Dec 2015). "Soluble epoxide hydrolase: A potential target for metabolic diseases". Journal of Diabetes. 8 (3): 305–13. doi: 10.1111/1753-0407.12358 . PMID   26621325.
  19. 1 2 3 Wagner K, Vito S, Inceoglu B, Hammock BD (Oct 2014). "The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling". Prostaglandins & Other Lipid Mediators. 113–115: 2–12. doi:10.1016/j.prostaglandins.2014.09.001. PMC   4254344 . PMID   25240260.
  20. ↑ 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 (Mar 2014). "Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway". Journal of Lipid Research. 55 (6): 1150–1164. doi: 10.1194/jlr.M047357 . PMC   4031946 . PMID   24634501.
  21. 1 2 3 4 5 Swedish environmental classification of pharmaceuticals Facts for prescribers (Fakta för förskrivare)
  22. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. Retrieved on July 2011
  23. ↑ "Assessment of Zopiclone" (PDF). World Health Organization. Essential Medicines and Health Products. World Health Organization. 2006. p. 9 (Section 5. Pharmacokinetics). Retrieved 5 December 2015.
  24. ↑ "Verapamil: Drug information. Lexicomp". UpToDate. Retrieved 2019-01-13.
  25. ↑ Fukuda T, Imai Y, Komori M, Nakamura M, Kusunose E, Satouchi K, Kusunose M (Jan 1993). "Replacement of Thr-303 of P450 2E1 with serine modifies the regioselectivity of its fatty acid hydroxylase activity". Journal of Biochemistry. 113 (1): 7–12. doi:10.1093/oxfordjournals.jbchem.a124006. PMID   8454577.
  26. ↑ Fukuda T, Imai Y, Komori M, Nakamura M, Kusunose E, Satouchi K, Kusunose M (Feb 1994). "Different mechanisms of regioselection of fatty acid hydroxylation by laurate (omega-1)-hydroxylating P450s, P450 2C2 and P450 2E1". Journal of Biochemistry. 115 (2): 338–44. doi:10.1093/oxfordjournals.jbchem.a124339. PMID   8206883.
  27. ↑ Kölble K (Dec 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.
  28. ↑ Raucy JL, Schultz ED, Wester MR, Arora S, Johnston DE, Omdahl JL, Carpenter SP (Dec 1997). "Human lymphocyte cytochrome P450 2E1, a putative marker for alcohol-mediated changes in hepatic chlorzoxazone activity". Drug Metabolism and Disposition. 25 (12): 1429–35. PMID   9394034.
  29. ↑ Desai HD, Seabolt J, Jann MW (2001). "Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective". CNS Drugs. 15 (6): 469–94. doi:10.2165/00023210-200115060-00005. PMID   11524025. S2CID   13197188.
  30. ↑ Lieber CS (Jun 1999). "Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968-1998)--a review". Alcoholism: Clinical and Experimental Research. 23 (6): 991–1007. doi:10.1111/j.1530-0277.1999.tb04217.x. PMID   10397283.
  31. ↑ Ray DC, Drummond GB (Jul 1991). "Halothane hepatitis". British Journal of Anaesthesia. 67 (1): 84–99. doi: 10.1093/bja/67.1.84 . PMID   1859766.
  32. ↑ Nanji AA, Zhao S, Sadrzadeh SM, Dannenberg AJ, Tahan SR, Waxman DJ (Oct 1994). "Markedly enhanced cytochrome P450 2E1 induction and lipid peroxidation is associated with severe liver injury in fish oil-ethanol-fed rats". Alcoholism: Clinical and Experimental Research. 18 (5): 1280–5. doi:10.1111/j.1530-0277.1994.tb00119.x. PMID   7847620.
  33. ↑ Koide CL, Collier AC, Berry MJ, Panee J (Jan 2011). "The effect of bamboo extract on hepatic biotransforming enzymes--findings from an obese-diabetic mouse model". Journal of Ethnopharmacology. 133 (1): 37–45. doi:10.1016/j.jep.2010.08.062. PMC   3471658 . PMID   20832461.
  34. ↑ Johansson I, Ekström G, Scholte B, Puzycki D, Jörnvall H, Ingelman-Sundberg M (Mar 1988). "Ethanol-, fasting-, and acetone-inducible cytochromes P-450 in rat liver: regulation and characteristics of enzymes belonging to the IIB and IIE gene subfamilies". Biochemistry. 27 (6): 1925–34. doi:10.1021/bi00406a019. PMID   3378038.
  35. ↑ Raucy JL, Lasker JM, Kraner JC, Salazar DE, Lieber CS, Corcoran GB (Mar 1991). "Induction of cytochrome P450IIE1 in the obese overfed rat". Molecular Pharmacology. 39 (3): 275–80. PMID   2005876.
  36. ↑ Kitam VO, Maksymchuk OV, Chashchyn MO (2012-12-17). "The possible mechanisms of CYP2E1 interactions with HSP90 and the influence of ethanol on them". BMC Structural Biology. 12 (1): 33. doi: 10.1186/1472-6807-12-33 . PMC   3544703 . PMID   23241420.
  37. ↑ 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 (Oct 2007). "Enhanced phytoremediation of volatile environmental pollutants with transgenic trees". Proceedings of the National Academy of Sciences of the United States of America. 104 (43): 16816–21. Bibcode:2007PNAS..10416816D. doi: 10.1073/pnas.0703276104 . PMC   2040402 . PMID   17940038.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.