Source:http://linkedlifedata.com/resource/pubmed/id/12460667
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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
2002-12-3
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pubmed:abstractText |
We synthesized novel ubiquinone analogs by hybridizing the natural ubiquinone ring (2,3-dimethoxy-5-methyl-1,4-benzoquinone) and hydrophobic phenoxybenzamide unit, and named them hybrid ubiquinones (HUs). The HUs worked as electron transfer substrates with bovine heart mitochondrial succinate-ubiquinone oxidoreductase (complex II) and ubiquinol-cytochrome c oxidoreductase (complex III), but not with NADH-ubiquinone oxidoreductase (complex I). With complex I, they acted as inhibitors in a noncompetitive manner against exogenous short-chain ubiquinones irrespective of the presence of the natural ubiquinone ring. Elongation of the distance between the ubiquinone ring and the phenoxybenzamide unit did not recover the electron accepting activity. The structure/activity study showed that high structural specificity of the phenoxybenzamide moiety is required to act as a potent inhibitor of complex I. These findings indicate that binding of the HUs to complex I is mainly decided by some specific interaction of the phenoxybenzamide moiety with the enzyme. It is of interest that an analogous bulky and hydrophobic substructure can be commonly found in recently registered synthetic pesticides the action site of which is mitochondrial complex I.
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pubmed:language |
eng
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Electron Transport Complex I,
http://linkedlifedata.com/resource/pubmed/chemical/Electron Transport Complex II,
http://linkedlifedata.com/resource/pubmed/chemical/Electron Transport Complex III,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/NADH, NADPH Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/Pesticides,
http://linkedlifedata.com/resource/pubmed/chemical/Succinate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquinone
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pubmed:status |
MEDLINE
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pubmed:author | |
pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
106-12
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pubmed:dateRevised |
2006-11-15
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pubmed:articleTitle |
Hybrid ubiquinone: novel inhibitor of mitochondrial complex I.
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pubmed:affiliation |
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kita-shirakawa, Sakyo-ku, 606-8502, Kyoto, Japan.
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