The mechanism of action of bacimethrin, a naturally occurring thiamin antimetabolite.
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.
Reddick
J J
JJ
Department of Chemistry and Chemical Biology, Cornell University, Baker Laboratory, Ithaca, NY 14853, USA.
Saha
S
S
Lee
J
J
Melnick
J S
JS
Perkins
J
J
Begley
T P
TP
D000963:Antimetabolites / Q000494:pharmacology*; D004798:Enzymes / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D007655:Ketoglutarate Dehydrogenase Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D005810:Multigene Family; D007652:Oxo-Acid-Lyases / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D013379:Substrate Specificity; D013831:Thiamine / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013835:Thiamine Pyrophosphate / Q000031:analogs & derivatives / Q000378:metabolism; D014174:Transketolase / Q000037:antagonists & inhibitors / Q000378:metabolism
C442364:2'-methoxythiamine pyrophosphate; D000963:Antimetabolites; D004798:Enzymes; D011743:Pyrimidines; C054356:bacimethrin; D007655:Ketoglutarate Dehydrogenase Complex; D014174:Transketolase; D017853:Phosphotransferases (Alcohol Group Acceptor); C059599:hydroxymethylpyrimidine kinase; C060510:2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase; D007652:Oxo-Acid-Lyases; D013835:Thiamine Pyrophosphate; D013831:Thiamine