Jump to content

Microsomal epoxide hydrolase: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Willchem (talk | contribs)
49 edits
Willchem (talk | contribs)
49 edits
edited photo
Line 9: Line 9:
| caption = A cartoon depiction of microsomal epoxide hydrolase from ''[[Aspergillus niger]]''
| caption = A cartoon depiction of microsomal epoxide hydrolase from ''[[Aspergillus niger]]''
}}
}}

In [[enzymology]], a '''microsomal epoxide hydrolase''' ({{EC number|3.3.2.9}}) is an [[enzyme]] that [[catalysis|catalyzes]] the [[hydrolysis]] reaction between an [[epoxide]] and [[water]] to form a [[diol]].<ref>{{cite book | vauthors = Durst F | chapter = Biochemistry and physiology of plant cytochrome P-450. | title = Microbial and Plant Cytochrome P-450: Biochemical Characteristics, Genetic Engineering and Practical Implications. Frontiers in biotransformation. | date = 1991 | volume = 4 | pages = 191–232 |doi=10.1002/nadc.19920400121 }}</ref>
In [[enzymology]], a '''microsomal epoxide hydrolase''' ({{EC number|3.3.2.9}}) is an [[enzyme]] that [[catalysis|catalyzes]] the [[hydrolysis]] reaction between an [[epoxide]] and [[water]] to form a [[diol]].<ref>{{cite book | vauthors = Durst F | chapter = Biochemistry and physiology of plant cytochrome P-450. | title = Microbial and Plant Cytochrome P-450: Biochemical Characteristics, Genetic Engineering and Practical Implications. Frontiers in biotransformation. | date = 1991 | volume = 4 | pages = 191–232 |doi=10.1002/nadc.19920400121 }}</ref>
[[File:Epoxide Hydrolysis.png|center|Hydrolysis of an epoxide ring|237x237px]]
[[File:Epoxide Hydrolysis.png|center|Hydrolysis of an epoxide ring|237x237px]]





Line 23: Line 25:


== Mechanism ==
== Mechanism ==
α/β-hydrolase fold enzymes utilize a [[Catalytic triad|catalytic triad]] in the active site. This catalytic triad is comprised of [[glutamine]], [[histidine]] and [[Aspartic acid|aspartic acid]].<ref>{{Cite journal|last=ARAND|first=Michael|last2=MÜLLER|first2=Frank|last3=MECKY|first3=Astrid|last4=HINZ|first4=Willy|last5=URBAN|first5=Phillipe|last6=POMPON|first6=Denis|last7=KELLNER|first7=Roland|last8=OESCH|first8=Franz|date=1999-01-01|title=Catalytic triad of microsomal epoxide hydrolase: replacement of Glu404 with Asp leads to a strongly increased turnover rate|url=http://dx.doi.org/10.1042/0264-6021:3370037|journal=Biochemical Journal|volume=337|issue=1|pages=37|doi=10.1042/0264-6021:3370037|issn=0264-6021}}</ref> The proposed mechanism for the mEH-catalyzed reaction first involves a [[nucleophilic attack]] on the [[Oxirene|oxirane]] ring on the substrate from the aspartic acid residue near the [[active site]], which forms an [[ester]] [[intermediate]].<ref>{{Cite journal|last=Lacourciere|first=Gerard M.|last2=Armstrong|first2=Richard N.|date=1993-11|title=The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate|url=http://dx.doi.org/10.1021/ja00075a115|journal=Journal of the American Chemical Society|volume=115|issue=22|pages=10466–10467|doi=10.1021/ja00075a115|issn=0002-7863}}</ref> The substrate is positioned in an orientation poised for nucleophilic attack by hydrogen bonding from two nearby [[tyrosine]] residues <ref name="Lewis_2005">{{cite journal | vauthors = Lewis DF, Lake BG, Bird MG | title = Molecular modelling of human microsomal epoxide hydrolase (EH) by homology with a fungal (Aspergillus niger) EH crystal structure of 1.8 A resolution: structure-activity relationships in epoxides inhibiting EH activity | journal = Toxicology in Vitro | volume = 19 | issue = 4 | pages = 517–22 | date = June 2005 | pmid = 15826809 | doi = 10.1016/j.tiv.2004.07.001 }}</ref><ref>{{cite journal | vauthors = Saenz-Méndez P, Katz A, Pérez-Kempner ML, Ventura ON, Vázquez M | title = Structural insights into human microsomal epoxide hydrolase by combined homology modeling, molecular dynamics simulations, and molecular docking calculations | journal = Proteins | volume = 85 | issue = 4 | pages = 720–730 | date = April 2017 | pmid = 28120429 | doi = 10.1002/prot.25251 }}</ref> The second step in this mechanism is [[hydrolysis]] of the ester that occurs by an activated water molecule.<ref name="McCall_2018">{{cite journal | vauthors = McCall PM, Srivastava S, Perry SL, Kovar DR, Gardel ML, Tirrell MV | title = Partitioning and Enhanced Self-Assembly of Actin in Polypeptide Coacervates | journal = Biophysical Journal | volume = 114 | issue = 7 | pages = 1636–1645 | date = April 2018 | pmid = 29642033 | pmc = 5954293 | doi = 10.1016/j.bpj.2018.02.020 | bibcode = 2018BpJ...114.1636M }}</ref> The activation of water is facilitated by proton abstraction via the charge relay system in the catalytic triad.<ref>{{cite journal | vauthors = Oesch F, Herrero ME, Hengstler JG, Lohmann M, Arand M | title = Metabolic detoxification: implications for thresholds | journal = Toxicologic Pathology | volume = 28 | issue = 3 | pages = 382–7 | date = May 2000 | pmid = 10862554 | doi = 10.1177/019262330002800305 }}</ref> After hydrolysis, the substrate is then released from its bond to [[aspartic acid]] and the free diol is formed.<ref>{{cite journal | vauthors = Reetz MT, Bocola M, Wang LW, Sanchis J, Cronin A, Arand M, Zou J, Archelas A, Bottalla AL, Naworyta A, Mowbray SL | title = Directed evolution of an enantioselective epoxide hydrolase: uncovering the source of enantioselectivity at each evolutionary stage | journal = Journal of the American Chemical Society | volume = 131 | issue = 21 | pages = 7334–43 | date = June 2009 | pmid = 19469578 | doi = 10.1021/ja809673d }}</ref>
α/β-hydrolase fold enzymes utilize a [[Catalytic triad|catalytic triad]] in the active site. This catalytic triad is comprised of [[glutamine]], [[histidine]] and [[Aspartic acid|aspartic acid]].<ref name=":0">{{Cite journal|last=ARAND|first=Michael|last2=MÜLLER|first2=Frank|last3=MECKY|first3=Astrid|last4=HINZ|first4=Willy|last5=URBAN|first5=Phillipe|last6=POMPON|first6=Denis|last7=KELLNER|first7=Roland|last8=OESCH|first8=Franz|date=1999-01-01|title=Catalytic triad of microsomal epoxide hydrolase: replacement of Glu404 with Asp leads to a strongly increased turnover rate|url=http://dx.doi.org/10.1042/0264-6021:3370037|journal=Biochemical Journal|volume=337|issue=1|pages=37|doi=10.1042/0264-6021:3370037|issn=0264-6021}}</ref> The proposed mechanism for the mEH-catalyzed reaction first involves a [[nucleophilic attack]] on the [[Oxirene|oxirane]] ring on the substrate from the aspartic acid residue near the [[active site]], which forms an [[ester]] [[intermediate]].<ref name=":1">{{Cite journal|last=Lacourciere|first=Gerard M.|last2=Armstrong|first2=Richard N.|date=1993-11|title=The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate|url=http://dx.doi.org/10.1021/ja00075a115|journal=Journal of the American Chemical Society|volume=115|issue=22|pages=10466–10467|doi=10.1021/ja00075a115|issn=0002-7863}}</ref> The substrate is positioned in an orientation poised for nucleophilic attack by hydrogen bonding from two nearby [[tyrosine]] residues <ref name="Lewis_2005">{{cite journal | vauthors = Lewis DF, Lake BG, Bird MG | title = Molecular modelling of human microsomal epoxide hydrolase (EH) by homology with a fungal (Aspergillus niger) EH crystal structure of 1.8 A resolution: structure-activity relationships in epoxides inhibiting EH activity | journal = Toxicology in Vitro | volume = 19 | issue = 4 | pages = 517–22 | date = June 2005 | pmid = 15826809 | doi = 10.1016/j.tiv.2004.07.001 }}</ref><ref name=":2">{{cite journal | vauthors = Saenz-Méndez P, Katz A, Pérez-Kempner ML, Ventura ON, Vázquez M | title = Structural insights into human microsomal epoxide hydrolase by combined homology modeling, molecular dynamics simulations, and molecular docking calculations | journal = Proteins | volume = 85 | issue = 4 | pages = 720–730 | date = April 2017 | pmid = 28120429 | doi = 10.1002/prot.25251 }}</ref> The second step in this mechanism is [[hydrolysis]] of the ester that occurs by an activated water molecule.<ref name="McCall_2018">{{cite journal | vauthors = McCall PM, Srivastava S, Perry SL, Kovar DR, Gardel ML, Tirrell MV | title = Partitioning and Enhanced Self-Assembly of Actin in Polypeptide Coacervates | journal = Biophysical Journal | volume = 114 | issue = 7 | pages = 1636–1645 | date = April 2018 | pmid = 29642033 | pmc = 5954293 | doi = 10.1016/j.bpj.2018.02.020 | bibcode = 2018BpJ...114.1636M }}</ref> The activation of water is facilitated by proton abstraction via the charge relay system in the catalytic triad.<ref>{{cite journal | vauthors = Oesch F, Herrero ME, Hengstler JG, Lohmann M, Arand M | title = Metabolic detoxification: implications for thresholds | journal = Toxicologic Pathology | volume = 28 | issue = 3 | pages = 382–7 | date = May 2000 | pmid = 10862554 | doi = 10.1177/019262330002800305 }}</ref> After hydrolysis, the substrate is then released from its bond to [[aspartic acid]] and the free diol is formed.<ref>{{cite journal | vauthors = Reetz MT, Bocola M, Wang LW, Sanchis J, Cronin A, Arand M, Zou J, Archelas A, Bottalla AL, Naworyta A, Mowbray SL | title = Directed evolution of an enantioselective epoxide hydrolase: uncovering the source of enantioselectivity at each evolutionary stage | journal = Journal of the American Chemical Society | volume = 131 | issue = 21 | pages = 7334–43 | date = June 2009 | pmid = 19469578 | doi = 10.1021/ja809673d }}</ref>


[[File:MEH-Mechanism.pdf|center|Chemical mechanism for microsomal epoxide hydrolase|alt=|444x444px]]
[[File:MEH-Mechanism.pdf|center|thumb|The mechanism of microsomal epoxide hydrolase<ref name=":0" /><ref name=":1" /><ref name="Lewis_2005" /><ref name=":2" />|350x350px]]


The active site of this enzyme lies within a [[Hydrophobe|hydrophobic]] pocket, which leads to the enzyme's preferential reactivity with molecules with hydrophobic [[Side chain|side-chains.]]<ref>{{cite journal | vauthors = Václavíková R, Hughes DJ, Souček P | title = Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease | journal = Gene | volume = 571 | issue = 1 | pages = 1–8 | date = October 2015 | pmid = 26216302 | pmc = 4544754 | doi = 10.1016/j.gene.2015.07.071 }}</ref><ref name="Lewis_2005" /> The mEH enzyme typically binds to small organic epoxides, such as styrene epoxide and cis-stillbene-oxide. mEH does not catalyze the hydrolysis of bulkier molecules, as their large side-chains may disrupt the charge relay system responsible for water activation.<ref name="Lewis_2005" />
The active site of this enzyme lies within a [[Hydrophobe|hydrophobic]] pocket, which leads to the enzyme's preferential reactivity with molecules with hydrophobic [[Side chain|side-chains.]]<ref>{{cite journal | vauthors = Václavíková R, Hughes DJ, Souček P | title = Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease | journal = Gene | volume = 571 | issue = 1 | pages = 1–8 | date = October 2015 | pmid = 26216302 | pmc = 4544754 | doi = 10.1016/j.gene.2015.07.071 }}</ref><ref name="Lewis_2005" /> The mEH enzyme typically binds to small organic epoxides, such as styrene epoxide and cis-stillbene-oxide. mEH does not catalyze the hydrolysis of bulkier molecules, as their large side-chains may disrupt the charge relay system responsible for water activation.<ref name="Lewis_2005" />

Revision as of 03:05, 15 March 2019

Microsomal epoxide hydrolase
A cartoon depiction of microsomal epoxide hydrolase from Aspergillus niger
Identifiers
EC no.3.3.2.9
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Search
PMCarticles
PubMedarticles
NCBIproteins

In enzymology, a microsomal epoxide hydrolase (EC 3.3.2.9) is an enzyme that catalyzes the hydrolysis reaction between an epoxide and water to form a diol.[1]

Hydrolysis of an epoxide ring
Hydrolysis of an epoxide ring


The human homolog of microsomal epoxide hydrolase is EPHX1. EPHX1 is located on chromosome 1.[2] This class of enzymes plays a role in the uptake of bile salts within the large intestine. It functions as a Na+ dependent transporter. This enzyme participates in metabolism of xenobiotics by cytochrome p450. mEH has been identified as playing a large role in the detoxification and bioactivation of a wide variety of substrates, such as polycyclic aromatic hydrocarbons (PAH), which are known for their carcinogenic properties.[3]

Nomenclature

This enzyme belongs to the family of hydrolases, specifically those acting on ether bonds (ether hydrolases). The systematic name of this enzyme class is cis-stilbene-oxide hydrolase. Other names in common use include epoxide hydratase (ambiguous), microsomal epoxide hydratase (ambiguous), epoxide hydrase, microsomal epoxide hydrase, arene-oxide hydratase (ambiguous), benzo[a]pyrene-4,5-oxide hydratase, benzo(a)pyrene-4,5-epoxide hydratase, aryl epoxide hydrase (ambiguous), cis-epoxide hydrolase, and mEH.

Structure

mEH belongs to the superfamily α/β-hydrolase fold enzymes.[4] The three dimensional structure of mEH has been elucidated from Aspergillus niger.[5] The enzyme is a single polypeptide chain composed of 455 amino acids. mEH has a molecular weight of 52.96 kilodaltons. It is known that the N-terminal region of the enzyme is responsible for anchoring the protein to the cellular membrane.[6] The C-terminal region of the enzyme contains catalytic residues.[5] Although no crystal structure has been solved for the mammalian mEH system (EPHX1), the overall homology between fungal and mammalian mEH is relatively high.[7][8][9] This high homology has helped to elucidate the overall structure and subsequent catalytic mechanism of EPHX1 in humans from existing crystal structures of fungal mEH.

Mechanism

α/β-hydrolase fold enzymes utilize a catalytic triad in the active site. This catalytic triad is comprised of glutamine, histidine and aspartic acid.[10] The proposed mechanism for the mEH-catalyzed reaction first involves a nucleophilic attack on the oxirane ring on the substrate from the aspartic acid residue near the active site, which forms an ester intermediate.[11] The substrate is positioned in an orientation poised for nucleophilic attack by hydrogen bonding from two nearby tyrosine residues [12][13] The second step in this mechanism is hydrolysis of the ester that occurs by an activated water molecule.[14] The activation of water is facilitated by proton abstraction via the charge relay system in the catalytic triad.[15] After hydrolysis, the substrate is then released from its bond to aspartic acid and the free diol is formed.[16]

The mechanism of microsomal epoxide hydrolase[10][11][12][13]

The active site of this enzyme lies within a hydrophobic pocket, which leads to the enzyme's preferential reactivity with molecules with hydrophobic side-chains.[17][12] The mEH enzyme typically binds to small organic epoxides, such as styrene epoxide and cis-stillbene-oxide. mEH does not catalyze the hydrolysis of bulkier molecules, as their large side-chains may disrupt the charge relay system responsible for water activation.[12]

mEH active site with small molecule 2-propoylpentanamide bound

Biological Function

In humans, mEH has been found in the ovary, lung, kidney, lymphocytes, epithelial cells, and liver.[18] Microsomal epoxide hydrolase serves as a protective enzyme against potentially harmful small molecules derived from the external environment.[19] This hydrolysis of genotoxic epoxides causes subsequent effects in several signal transduction pathways, rendering this enzyme important to metabolism.[20][21]

Disease relevance

Microsomal epoxide hydrolase plays a large role in the regulation of human health. Studies have shown that mutations EPHX1 in humans may be the cause of hypercholanemia,[22] preeclampsia,[23][24] and may contribute to fetal hydantoin syndrome.[25] It is also suggested that maternal polymorphisms in EPHX1 in pregnant women were related to facial malformations of children born from women taking phenytoin during their first trimester of pregnancy.[26] While mEH participates in the protection of human health via detoxification of various environmental substances, it also has been found to facilitate the activation of carcinogens.[3]

mEH detoxifies reactive epoxides that are commonly caused from cigarette smoke, and as such it has been hypothesized that mutations in EPHX1 in humans may have an effect on an individual's susceptibility to COPD, emphysema and lung cancer. Some sources have demonstrated that individuals affected by COPD have a higher rate of containing an under-active variant of the EPHX1 gene, yet also demonstrated that the overactive variant of the gene was also found in higher frequencies in individuals affected by disease a well.[27][28] It has also been suggested that the EPHX1 variants do not contribute to susceptibility of disease, but do contribute to disease severity.[29] The role that mEH plays in lung cancer and COPD is still not fully elucidated, as the data on the topic in the literature is not fully clear.[30] There is some evidence that mEH variants may contribute to the occurrence of childhood asthma in combination with variants on the GSTP1 gene.[31]

References

  1. ^ Durst F (1991). "Biochemistry and physiology of plant cytochrome P-450.". Microbial and Plant Cytochrome P-450: Biochemical Characteristics, Genetic Engineering and Practical Implications. Frontiers in biotransformation. Vol. 4. pp. 191–232. doi:10.1002/nadc.19920400121.
  2. ^ Jackson MR, Craft JA, Burchell B (September 1987). "Nucleotide and deduced amino acid sequence of human liver microsomal epoxide hydrolase". Nucleic Acids Research. 15 (17): 7188. doi:10.1093/nar/15.17.7188. PMC 306212. PMID 3502697.
  3. ^ a b Kiyohara C, Yoshimasu K, Takayama K, Nakanishi Y (January 2006). "EPHX1 polymorphisms and the risk of lung cancer: a HuGE review". Epidemiology (Cambridge, Mass.). 17 (1): 89–99. doi:10.1097/01.ede.0000187627.70026.23. PMID 16357600.
  4. ^ Ollis DL, Cheah E, Cygler M, Dijkstra B, Frolow F, Franken SM, Harel M, Remington SJ, Silman I, Schrag J, Sussman JL (April 1992). "The α/β hydrolase fold. Protein Engineering, Design and Selection". 5 (3): 197–211. doi:10.1093/protein/5.3.197. {{cite journal}}: Cite journal requires |journal= (help)
  5. ^ a b PDB: 3G0I​; Zou J, Hallberg BM, Bergfors T, Oesch F, Arand M, Mowbray SL, Jones TA (February 2000). "Structure of Aspergillus niger epoxide hydrolase at 1.8 A resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases". Structure (London, England : 1993). 8 (2): 111–22. doi:10.1016/S0969-2126(00)00087-3. PMID 10673439.
  6. ^ Craft JA, Baird S, Lamont M, Burchell B (August 1990). "Membrane topology of epoxide hydrolase". Biochimica et Biophysica Acta. 1046 (1): 32–9. doi:10.1016/0005-2760(90)90091-B. PMID 2397243.
  7. ^ Arand, Michael; Oesch, Franz (2002-02-14). Mammalian Xenobiotic Epoxide Hydrolases. John Wiley & Sons, Ltd. pp. 459–483. doi:10.1002/0470846305.ch12. ISBN 9780470846308. {{cite book}}: |work= ignored (help); Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  8. ^ Arand M, Hemmer H, Dürk H, Baratti J, Archelas A, Furstoss R, Oesch F (November 1999). "Cloning and molecular characterization of a soluble epoxide hydrolase from Aspergillus niger that is related to mammalian microsomal epoxide hydrolase". The Biochemical Journal. 344 Pt 1 (1): 273–80. doi:10.1042/0264-6021:3440273. PMID 10548561.
  9. ^ Arand M, Müller F, Mecky A, Hinz W, Urban P, Pompon D, Kellner R, Oesch F (January 1999). "Catalytic triad of microsomal epoxide hydrolase: replacement of Glu404 with Asp leads to a strongly increased turnover rate". The Biochemical Journal. 337 ( Pt 1) (1): 37–43. doi:10.1042/0264-6021:3370037. PMID 9854022.
  10. ^ a b ARAND, Michael; MÜLLER, Frank; MECKY, Astrid; HINZ, Willy; URBAN, Phillipe; POMPON, Denis; KELLNER, Roland; OESCH, Franz (1999-01-01). "Catalytic triad of microsomal epoxide hydrolase: replacement of Glu404 with Asp leads to a strongly increased turnover rate". Biochemical Journal. 337 (1): 37. doi:10.1042/0264-6021:3370037. ISSN 0264-6021.
  11. ^ a b Lacourciere, Gerard M.; Armstrong, Richard N. (1993-11). "The catalytic mechanism of microsomal epoxide hydrolase involves an ester intermediate". Journal of the American Chemical Society. 115 (22): 10466–10467. doi:10.1021/ja00075a115. ISSN 0002-7863. {{cite journal}}: Check date values in: |date= (help)
  12. ^ a b c d Lewis DF, Lake BG, Bird MG (June 2005). "Molecular modelling of human microsomal epoxide hydrolase (EH) by homology with a fungal (Aspergillus niger) EH crystal structure of 1.8 A resolution: structure-activity relationships in epoxides inhibiting EH activity". Toxicology in Vitro. 19 (4): 517–22. doi:10.1016/j.tiv.2004.07.001. PMID 15826809.
  13. ^ a b Saenz-Méndez P, Katz A, Pérez-Kempner ML, Ventura ON, Vázquez M (April 2017). "Structural insights into human microsomal epoxide hydrolase by combined homology modeling, molecular dynamics simulations, and molecular docking calculations". Proteins. 85 (4): 720–730. doi:10.1002/prot.25251. PMID 28120429.
  14. ^ McCall PM, Srivastava S, Perry SL, Kovar DR, Gardel ML, Tirrell MV (April 2018). "Partitioning and Enhanced Self-Assembly of Actin in Polypeptide Coacervates". Biophysical Journal. 114 (7): 1636–1645. Bibcode:2018BpJ...114.1636M. doi:10.1016/j.bpj.2018.02.020. PMC 5954293. PMID 29642033.
  15. ^ Oesch F, Herrero ME, Hengstler JG, Lohmann M, Arand M (May 2000). "Metabolic detoxification: implications for thresholds". Toxicologic Pathology. 28 (3): 382–7. doi:10.1177/019262330002800305. PMID 10862554.
  16. ^ Reetz MT, Bocola M, Wang LW, Sanchis J, Cronin A, Arand M, Zou J, Archelas A, Bottalla AL, Naworyta A, Mowbray SL (June 2009). "Directed evolution of an enantioselective epoxide hydrolase: uncovering the source of enantioselectivity at each evolutionary stage". Journal of the American Chemical Society. 131 (21): 7334–43. doi:10.1021/ja809673d. PMID 19469578.
  17. ^ Václavíková R, Hughes DJ, Souček P (October 2015). "Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease". Gene. 571 (1): 1–8. doi:10.1016/j.gene.2015.07.071. PMC 4544754. PMID 26216302.
  18. ^ Bachmann, Kenneth (2009). "Chapter 8: Drug Metabolism". Pharmacology. Elsevier. pp. 131–173. doi:10.1016/b978-0-12-369521-5.00008-7. ISBN 978-0-12-369521-5. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  19. ^ Oesch F (May 1973). "Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds". Xenobiotica; The Fate of Foreign Compounds in Biological Systems. 3 (5): 305–40. doi:10.3109/00498257309151525. PMID 4584115.
  20. ^ Samuelsson B, Dahlén SE, Lindgren JA, Rouzer CA, Serhan CN (September 1987). "Leukotrienes and lipoxins: structures, biosynthesis, and biological effects". Science. 237 (4819): 1171–6. doi:10.1126/science.2820055. PMID 2820055.
  21. ^ Moghaddam MF, Grant DF, Cheek JM, Greene JF, Williamson KC, Hammock BD (May 1997). "Bioactivation of leukotoxins to their toxic diols by epoxide hydrolase". Nature Medicine. 3 (5): 562–6. doi:10.1038/nm0597-562. PMID 9142128.
  22. ^ Zhu QS, Xing W, Qian B, von Dippe P, Shneider BL, Fox VL, Levy D (July 2003). "Inhibition of human m-epoxide hydrolase gene expression in a case of hypercholanemia". Biochimica et Biophysica Acta. 1638 (3): 208–16. doi:10.1016/s0925-4439(03)00085-1. PMID 12878321.
  23. ^ Zusterzeel PL, Rütten H, Roelofs HM, Peters WH, Steegers EA (February 2001). "Protein carbonyls in decidua and placenta of pre-eclamptic women as markers for oxidative stress". Placenta. 22 (2–3): 213–9. doi:10.1053/plac.2000.0606. PMID 11170826.
  24. ^ Laasanen J, Romppanen EL, Hiltunen M, Helisalmi S, Mannermaa A, Punnonen K, Heinonen S (September 2002). "Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are jointly associated with preeclampsia". European Journal of Human Genetics. 10 (9): 569–73. doi:10.1038/sj.ejhg.5200849. PMID 12173035.
  25. ^ Buehler BA, Delimont D, van Waes M, Finnell RH (May 1990). "Prenatal prediction of risk of the fetal hydantoin syndrome". The New England Journal of Medicine. 322 (22): 1567–72. doi:10.1097/00132582-199010000-00007. PMID 2336087.
  26. ^ Azzato EM, Chen RA, Wacholder S, Chanock SJ, Klebanoff MA, Caporaso NE (January 2010). "Maternal EPHX1 polymorphisms and risk of phenytoin-induced congenital malformations". Pharmacogenetics and Genomics. 20 (1): 58–63. doi:10.1097/fpc.0b013e328334b6a3. PMID 19952982.
  27. ^ Smith CA, Harrison DJ (August 1997). "Association between polymorphism in gene for microsomal epoxide hydrolase and susceptibility to emphysema". Lancet. 350 (9078): 630–3. doi:10.1016/s0140-6736(96)08061-0. PMID 9288046.
  28. ^ Brøgger J, Steen VM, Eiken HG, Gulsvik A, Bakke P (April 2006). "Genetic association between COPD and polymorphisms in TNF, ADRB2 and EPHX1". The European Respiratory Journal. 27 (4): 682–8. doi:10.1183/09031936.06.00057005. PMID 16585076.
  29. ^ Kiyohara C, Yoshimasu K, Takayama K, Nakanishi Y (January 2006). "EPHX1 polymorphisms and the risk of lung cancer: a HuGE review". Epidemiology. 17 (1): 89–99. doi:10.1097/01.ede.0000187627.70026.23. PMID 16357600.
  30. ^ Postma, Dirkje S.; Silverman, Edwin K. (2009). "Chapter 4 - Genetics of Asthma and COPD". Genetics of Asthma and COPD. Elsevier. pp. 37–51. doi:10.1016/b978-0-12-374001-4.00004-3. ISBN 9780123740014. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  31. ^ Salam, M. T; Lin, P.-C.; Avol, E. L; Gauderman, W J.; Gilliland, F. D (2007-12-01). "Microsomal epoxide hydrolase, glutathione S-transferase P1, traffic and childhood asthma". Thorax. 62 (12): 1050–1057. doi:10.1136/thx.2007.080127. ISSN 0040-6376.

Further reading

Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Microsomal_epoxide_hydrolase&oldid=887830216"