Abstract
The mechanism of bacimethrin (2) toxicity has been determined. This compound is converted to 2'-methoxy-thiamin pyrophosphate (10) by the thiamin biosynthetic enzymes. Of the seven thiamin pyrophosphate utilizing enzymes in Escherichia coli, 2'-methoxy-thiamin pyrophosphate inhibits alpha-ketoglutarate dehydrogenase, transketolase, and deoxy-D-xylulose-5-phosphate synthase. Bacimethrin does not cause repression of the genes coding for the thiamin biosynthetic enzymes.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antimetabolites / pharmacology*
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Enzymes / metabolism
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression Regulation, Enzymologic
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Ketoglutarate Dehydrogenase Complex / antagonists & inhibitors
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Ketoglutarate Dehydrogenase Complex / metabolism
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Multigene Family
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Oxo-Acid-Lyases / genetics
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Oxo-Acid-Lyases / metabolism
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Pyrimidines / pharmacology*
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Substrate Specificity
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Thiamine / antagonists & inhibitors*
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Thiamine / metabolism*
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Thiamine Pyrophosphate / analogs & derivatives
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Thiamine Pyrophosphate / metabolism
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Transketolase / antagonists & inhibitors
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Transketolase / metabolism
Substances
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2'-methoxythiamine pyrophosphate
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Antimetabolites
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Enzymes
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Pyrimidines
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bacimethrin
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Ketoglutarate Dehydrogenase Complex
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Transketolase
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Phosphotransferases (Alcohol Group Acceptor)
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hydroxymethylpyrimidine kinase
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2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase
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Oxo-Acid-Lyases
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Thiamine Pyrophosphate
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Thiamine