Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A
General acyl-CoA dehydrogenase (GAD) is a flavin-dependent (FAD) enzyme that catalyzes the oxidation of a fatty acyl-CoA to the corresponding alpha , beta -enolyl-CoA. When GAD is exposed to (methylenecyclopropyl)-acetyl-CoA (MCPA-CoA) a metabolite of hypoglycin A that is the causative agent of Jama...
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| Veröffentlicht in: | Journal of the American Chemical Society 1991-09, Vol.113 (19), p.7388-7397 |
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| container_title | Journal of the American Chemical Society |
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| creator | Lai, Ming Tain Liu, Li Da Liu, Hung Wen |
| description | General acyl-CoA dehydrogenase (GAD) is a flavin-dependent (FAD) enzyme that catalyzes the oxidation of a fatty acyl-CoA to the corresponding alpha , beta -enolyl-CoA. When GAD is exposed to (methylenecyclopropyl)-acetyl-CoA (MCPA-CoA) a metabolite of hypoglycin A that is the causative agent of Jamaican vomiting sickness, time-dependent inhibition occurs with concomitant bleaching of the active-site FAD. The inactivation mechanism is generally believed to be initiated by C sub( alpha ) anion formation followed by ring fragmentation and the covalent modification of FAD. However, formation of a cyclopropyl radical intermediate through one-electron oxidation followed by ring opening and then radical recombination to yield a modified FAD is an appealing alternative. The mechanistic insights deduced from this study support our early notion that inactivation of GAD by MCPA-CoA is likely to proceed through a radical mechanism. |
| doi_str_mv | 10.1021/ja00019a040 |
| format | Article |
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When GAD is exposed to (methylenecyclopropyl)-acetyl-CoA (MCPA-CoA) a metabolite of hypoglycin A that is the causative agent of Jamaican vomiting sickness, time-dependent inhibition occurs with concomitant bleaching of the active-site FAD. The inactivation mechanism is generally believed to be initiated by C sub( alpha ) anion formation followed by ring fragmentation and the covalent modification of FAD. However, formation of a cyclopropyl radical intermediate through one-electron oxidation followed by ring opening and then radical recombination to yield a modified FAD is an appealing alternative. The mechanistic insights deduced from this study support our early notion that inactivation of GAD by MCPA-CoA is likely to proceed through a radical mechanism.</description><identifier>ISSN: 0002-7863</identifier><identifier>EISSN: 1520-5126</identifier><identifier>DOI: 10.1021/ja00019a040</identifier><identifier>CODEN: JACSAT</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>acyl-CoA dehydrogenase ; Atomic and molecular physics ; Exact sciences and technology ; hypoglycin A ; inhibition ; mechanisms ; metabolites ; Molecular properties and interactions with photons ; Nuclear resonance and relaxation ; Physics</subject><ispartof>Journal of the American Chemical Society, 1991-09, Vol.113 (19), p.7388-7397</ispartof><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a361t-38f9c789b07e359826b54f02c11444f7e6d7810c4423871bb47cb18329e2ef4d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ja00019a040$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ja00019a040$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4440673$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Lai, Ming Tain</creatorcontrib><creatorcontrib>Liu, Li Da</creatorcontrib><creatorcontrib>Liu, Hung Wen</creatorcontrib><title>Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A</title><title>Journal of the American Chemical Society</title><addtitle>J. Am. Chem. Soc</addtitle><description>General acyl-CoA dehydrogenase (GAD) is a flavin-dependent (FAD) enzyme that catalyzes the oxidation of a fatty acyl-CoA to the corresponding alpha , beta -enolyl-CoA. When GAD is exposed to (methylenecyclopropyl)-acetyl-CoA (MCPA-CoA) a metabolite of hypoglycin A that is the causative agent of Jamaican vomiting sickness, time-dependent inhibition occurs with concomitant bleaching of the active-site FAD. The inactivation mechanism is generally believed to be initiated by C sub( alpha ) anion formation followed by ring fragmentation and the covalent modification of FAD. However, formation of a cyclopropyl radical intermediate through one-electron oxidation followed by ring opening and then radical recombination to yield a modified FAD is an appealing alternative. The mechanistic insights deduced from this study support our early notion that inactivation of GAD by MCPA-CoA is likely to proceed through a radical mechanism.</description><subject>acyl-CoA dehydrogenase</subject><subject>Atomic and molecular physics</subject><subject>Exact sciences and technology</subject><subject>hypoglycin A</subject><subject>inhibition</subject><subject>mechanisms</subject><subject>metabolites</subject><subject>Molecular properties and interactions with photons</subject><subject>Nuclear resonance and relaxation</subject><subject>Physics</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><recordid>eNptkEFPGzEQha0KpKaBE3_Ah6o9VFtsr3e9e0zTQpFAoCZcuFiz3tnE6WYdbKdi_32NghAHTqN5873R0yPkjLPvnAl-vgHGGK-BSfaBTHghWFZwUR6RSdJFpqoy_0g-hbBJqxQVn5DVDZo1DDZEa2iI-3akbqBxjdQOYKL9B9EmwXV0hQN66CmYsc_mbkZbXI-td0mHgLQZKdAtRmhcbyM-O9bjzq360diBzk7IcQd9wNOXOSX3F7-W89_Z9e3l1Xx2nUFe8pjlVVcbVdUNU5gXdSXKppAdE4ZzKWWnsGxVxZmRUuSV4k0jlWl4lYsaBXayzafky-HvzrvHPYaotzYY7HsY0O2D5mUy1mWRwG8H0HgXgsdO77zdgh81Z_q5TP2mzER_fnkLwUDfeRiMDa-WlI2VKk9YdsBSn_j0egb_V6ezKvTybqEvFg8_xY8_SsvEfz3wYILeuL0fUjfvBvgPCzmOyA</recordid><startdate>19910901</startdate><enddate>19910901</enddate><creator>Lai, Ming Tain</creator><creator>Liu, Li Da</creator><creator>Liu, Hung Wen</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M81</scope><scope>P64</scope></search><sort><creationdate>19910901</creationdate><title>Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A</title><author>Lai, Ming Tain ; Liu, Li Da ; Liu, Hung Wen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a361t-38f9c789b07e359826b54f02c11444f7e6d7810c4423871bb47cb18329e2ef4d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>acyl-CoA dehydrogenase</topic><topic>Atomic and molecular physics</topic><topic>Exact sciences and technology</topic><topic>hypoglycin A</topic><topic>inhibition</topic><topic>mechanisms</topic><topic>metabolites</topic><topic>Molecular properties and interactions with photons</topic><topic>Nuclear resonance and relaxation</topic><topic>Physics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lai, Ming Tain</creatorcontrib><creatorcontrib>Liu, Li Da</creatorcontrib><creatorcontrib>Liu, Hung Wen</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 3</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lai, Ming Tain</au><au>Liu, Li Da</au><au>Liu, Hung Wen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>1991-09-01</date><risdate>1991</risdate><volume>113</volume><issue>19</issue><spage>7388</spage><epage>7397</epage><pages>7388-7397</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><coden>JACSAT</coden><abstract>General acyl-CoA dehydrogenase (GAD) is a flavin-dependent (FAD) enzyme that catalyzes the oxidation of a fatty acyl-CoA to the corresponding alpha , beta -enolyl-CoA. When GAD is exposed to (methylenecyclopropyl)-acetyl-CoA (MCPA-CoA) a metabolite of hypoglycin A that is the causative agent of Jamaican vomiting sickness, time-dependent inhibition occurs with concomitant bleaching of the active-site FAD. The inactivation mechanism is generally believed to be initiated by C sub( alpha ) anion formation followed by ring fragmentation and the covalent modification of FAD. However, formation of a cyclopropyl radical intermediate through one-electron oxidation followed by ring opening and then radical recombination to yield a modified FAD is an appealing alternative. The mechanistic insights deduced from this study support our early notion that inactivation of GAD by MCPA-CoA is likely to proceed through a radical mechanism.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><doi>10.1021/ja00019a040</doi><tpages>10</tpages></addata></record> |
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| source | American Chemical Society Journals |
| subjects | acyl-CoA dehydrogenase Atomic and molecular physics Exact sciences and technology hypoglycin A inhibition mechanisms metabolites Molecular properties and interactions with photons Nuclear resonance and relaxation Physics |
| title | Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A |
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