Heterologous expression of human microsomal epoxide hydrolase in saccharomyces cerevisiae: Study of the valpromide-carbamazepine epoxide interaction
A cDNA of human microsomal epoxide hydrolase (hmEH) was constitutively and inducibly expressed in Saccharomyces cerevisiae.The heterologous enzyme was located mainly in the microsomal fraction of yeast cells. Yeast microsomes containing hmEH exerted styrene oxide hydrolase activity ( K m = 300 μM; V...
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| Veröffentlicht in: | Biochemical pharmacology 1991-09, Vol.42 (7), p.1367-1372 |
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| creator | Eugster, Hans-Pietro Sengstag, Christian Hinnen, Albert Meyer, Urs A. Wügler, Friedrich E. |
| description | A cDNA of human microsomal epoxide hydrolase (hmEH) was constitutively and inducibly expressed in
Saccharomyces cerevisiae.The heterologous enzyme was located mainly in the microsomal fraction of yeast cells. Yeast microsomes containing hmEH exerted styrene oxide hydrolase activity (
K
m
= 300
μM;
V
max = 22 nmol/mg min) as well as carbamazepine epoxide hydrolase activity. The hmEH catalysed exclusively the formation of carbamazepine-10,11-transdihydrodiol, since no carbamazepine-10, 11-cisdihydrodiol was detected. Inhibition studies using these microsomes revealed unequivocally hmEH as the target for inhibition by the antiepileptic drug valproroide. A
K
i
value of 27 μM was determined for the inhibitor valpromide with styrene oxide as substrate. For carbamazepine epoxide, a
K
i
value of 8.6 μM was obtained, which is well in line with data published for hmEH determined with human liver microsomes. Our results demonstrate the potential of heterologous gene expression in
S.cerevisiae and its application to the
in vitro study of pharmacological and toxicological problems. |
| doi_str_mv | 10.1016/0006-2952(91)90447-D |
| format | Article |
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Saccharomyces cerevisiae.The heterologous enzyme was located mainly in the microsomal fraction of yeast cells. Yeast microsomes containing hmEH exerted styrene oxide hydrolase activity (
K
m
= 300
μM;
V
max = 22 nmol/mg min) as well as carbamazepine epoxide hydrolase activity. The hmEH catalysed exclusively the formation of carbamazepine-10,11-transdihydrodiol, since no carbamazepine-10, 11-cisdihydrodiol was detected. Inhibition studies using these microsomes revealed unequivocally hmEH as the target for inhibition by the antiepileptic drug valproroide. A
K
i
value of 27 μM was determined for the inhibitor valpromide with styrene oxide as substrate. For carbamazepine epoxide, a
K
i
value of 8.6 μM was obtained, which is well in line with data published for hmEH determined with human liver microsomes. Our results demonstrate the potential of heterologous gene expression in
S.cerevisiae and its application to the
in vitro study of pharmacological and toxicological problems.</description><identifier>ISSN: 0006-2952</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/0006-2952(91)90447-D</identifier><identifier>PMID: 1930259</identifier><identifier>CODEN: BCPCA6</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Analytical, structural and metabolic biochemistry ; Base Sequence ; Biological and medical sciences ; Carbamazepine - analogs & derivatives ; Carbamazepine - metabolism ; Drug Interactions ; Enzymes and enzyme inhibitors ; Epoxide Hydrolases - antagonists & inhibitors ; Epoxide Hydrolases - genetics ; Epoxy Compounds - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Enzymologic ; Humans ; Hydrolases ; Kinetics ; Microsomes - drug effects ; Microsomes - enzymology ; Molecular Sequence Data ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae - genetics ; Styrenes - metabolism ; Valproic Acid - analogs & derivatives ; Valproic Acid - pharmacology</subject><ispartof>Biochemical pharmacology, 1991-09, Vol.42 (7), p.1367-1372</ispartof><rights>1991</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0006-2952(91)90447-D$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5025236$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1930259$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eugster, Hans-Pietro</creatorcontrib><creatorcontrib>Sengstag, Christian</creatorcontrib><creatorcontrib>Hinnen, Albert</creatorcontrib><creatorcontrib>Meyer, Urs A.</creatorcontrib><creatorcontrib>Wügler, Friedrich E.</creatorcontrib><title>Heterologous expression of human microsomal epoxide hydrolase in saccharomyces cerevisiae: Study of the valpromide-carbamazepine epoxide interaction</title><title>Biochemical pharmacology</title><addtitle>Biochem Pharmacol</addtitle><description>A cDNA of human microsomal epoxide hydrolase (hmEH) was constitutively and inducibly expressed in
Saccharomyces cerevisiae.The heterologous enzyme was located mainly in the microsomal fraction of yeast cells. Yeast microsomes containing hmEH exerted styrene oxide hydrolase activity (
K
m
= 300
μM;
V
max = 22 nmol/mg min) as well as carbamazepine epoxide hydrolase activity. The hmEH catalysed exclusively the formation of carbamazepine-10,11-transdihydrodiol, since no carbamazepine-10, 11-cisdihydrodiol was detected. Inhibition studies using these microsomes revealed unequivocally hmEH as the target for inhibition by the antiepileptic drug valproroide. A
K
i
value of 27 μM was determined for the inhibitor valpromide with styrene oxide as substrate. For carbamazepine epoxide, a
K
i
value of 8.6 μM was obtained, which is well in line with data published for hmEH determined with human liver microsomes. Our results demonstrate the potential of heterologous gene expression in
S.cerevisiae and its application to the
in vitro study of pharmacological and toxicological problems.</description><subject>Analytical, structural and metabolic biochemistry</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Carbamazepine - analogs & derivatives</subject><subject>Carbamazepine - metabolism</subject><subject>Drug Interactions</subject><subject>Enzymes and enzyme inhibitors</subject><subject>Epoxide Hydrolases - antagonists & inhibitors</subject><subject>Epoxide Hydrolases - genetics</subject><subject>Epoxy Compounds - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Humans</subject><subject>Hydrolases</subject><subject>Kinetics</subject><subject>Microsomes - drug effects</subject><subject>Microsomes - enzymology</subject><subject>Molecular Sequence Data</subject><subject>Saccharomyces cerevisiae</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Styrenes - metabolism</subject><subject>Valproic Acid - analogs & derivatives</subject><subject>Valproic Acid - pharmacology</subject><issn>0006-2952</issn><issn>1873-2968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kcFu1DAQhi0EKtvCG4DkA0LlEPDYiRP3gIRaoEiVOABna-LMskZJHOxk1eU5eGAcutrTyDPf_DOen7EXIN6CAP1OCKELaSp5aeCNEWVZFzeP2AaaWuW0bh6zzQl5ys5T-rU-Gw1n7AyMErIyG_b3lmaKoQ8_w5I43U-RUvJh5GHLd8uAIx-8iyGFAXtOU7j3HfHdocstmIj7kSd0bocxDAdHiTuKtPfJI13xb_PSHVaheUd8j_2UodxeOIwtDviHJj_SSdSPeRF0cx7-jD3ZYp_o-TFesB-fPn6_vi3uvn7-cv3hriAlYS4MCVXrFlRZuaqupKy7spRoTNkpozupq1aTaA3URrTgGgOCGgmtQmVaaoS6YK8fdPNmvxdKsx18ctT3OFI-hwUN0JSizODLI7i0A3V2in7AeLDHM-b6q2Mdk8N-G3F0Pp2wKkNS6Yy9f8Aof2rvKdrkPI2OOh_JzbYL3oKwq7t29cqu1lkD9r-79kb9A2AkmNg</recordid><startdate>19910912</startdate><enddate>19910912</enddate><creator>Eugster, Hans-Pietro</creator><creator>Sengstag, Christian</creator><creator>Hinnen, Albert</creator><creator>Meyer, Urs A.</creator><creator>Wügler, Friedrich E.</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TM</scope><scope>M7N</scope></search><sort><creationdate>19910912</creationdate><title>Heterologous expression of human microsomal epoxide hydrolase in saccharomyces cerevisiae: Study of the valpromide-carbamazepine epoxide interaction</title><author>Eugster, Hans-Pietro ; Sengstag, Christian ; Hinnen, Albert ; Meyer, Urs A. ; Wügler, Friedrich E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e321t-9e0376b1345c575227d442a994d396d265b6e0b91790b1c8910e821b3a39be803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Analytical, structural and metabolic biochemistry</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Carbamazepine - analogs & derivatives</topic><topic>Carbamazepine - metabolism</topic><topic>Drug Interactions</topic><topic>Enzymes and enzyme inhibitors</topic><topic>Epoxide Hydrolases - antagonists & inhibitors</topic><topic>Epoxide Hydrolases - genetics</topic><topic>Epoxy Compounds - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Humans</topic><topic>Hydrolases</topic><topic>Kinetics</topic><topic>Microsomes - drug effects</topic><topic>Microsomes - enzymology</topic><topic>Molecular Sequence Data</topic><topic>Saccharomyces cerevisiae</topic><topic>Saccharomyces cerevisiae - genetics</topic><topic>Styrenes - metabolism</topic><topic>Valproic Acid - analogs & derivatives</topic><topic>Valproic Acid - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eugster, Hans-Pietro</creatorcontrib><creatorcontrib>Sengstag, Christian</creatorcontrib><creatorcontrib>Hinnen, Albert</creatorcontrib><creatorcontrib>Meyer, Urs A.</creatorcontrib><creatorcontrib>Wügler, Friedrich E.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Nucleic Acids Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eugster, Hans-Pietro</au><au>Sengstag, Christian</au><au>Hinnen, Albert</au><au>Meyer, Urs A.</au><au>Wügler, Friedrich E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heterologous expression of human microsomal epoxide hydrolase in saccharomyces cerevisiae: Study of the valpromide-carbamazepine epoxide interaction</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>1991-09-12</date><risdate>1991</risdate><volume>42</volume><issue>7</issue><spage>1367</spage><epage>1372</epage><pages>1367-1372</pages><issn>0006-2952</issn><eissn>1873-2968</eissn><coden>BCPCA6</coden><abstract>A cDNA of human microsomal epoxide hydrolase (hmEH) was constitutively and inducibly expressed in
Saccharomyces cerevisiae.The heterologous enzyme was located mainly in the microsomal fraction of yeast cells. Yeast microsomes containing hmEH exerted styrene oxide hydrolase activity (
K
m
= 300
μM;
V
max = 22 nmol/mg min) as well as carbamazepine epoxide hydrolase activity. The hmEH catalysed exclusively the formation of carbamazepine-10,11-transdihydrodiol, since no carbamazepine-10, 11-cisdihydrodiol was detected. Inhibition studies using these microsomes revealed unequivocally hmEH as the target for inhibition by the antiepileptic drug valproroide. A
K
i
value of 27 μM was determined for the inhibitor valpromide with styrene oxide as substrate. For carbamazepine epoxide, a
K
i
value of 8.6 μM was obtained, which is well in line with data published for hmEH determined with human liver microsomes. Our results demonstrate the potential of heterologous gene expression in
S.cerevisiae and its application to the
in vitro study of pharmacological and toxicological problems.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>1930259</pmid><doi>10.1016/0006-2952(91)90447-D</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Biochemical pharmacology, 1991-09, Vol.42 (7), p.1367-1372 |
| issn | 0006-2952 1873-2968 |
| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Analytical, structural and metabolic biochemistry Base Sequence Biological and medical sciences Carbamazepine - analogs & derivatives Carbamazepine - metabolism Drug Interactions Enzymes and enzyme inhibitors Epoxide Hydrolases - antagonists & inhibitors Epoxide Hydrolases - genetics Epoxy Compounds - metabolism Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Enzymologic Humans Hydrolases Kinetics Microsomes - drug effects Microsomes - enzymology Molecular Sequence Data Saccharomyces cerevisiae Saccharomyces cerevisiae - genetics Styrenes - metabolism Valproic Acid - analogs & derivatives Valproic Acid - pharmacology |
| title | Heterologous expression of human microsomal epoxide hydrolase in saccharomyces cerevisiae: Study of the valpromide-carbamazepine epoxide interaction |
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