title: Toxic accumulation of alpha-ketobutyrate caused by inhibition of the branched-chain amino acid biosynthetic enzyme acetolactate synthase in Salmonella typhimurium.
abstract: Biochemical and genetic analyses of the bacterium Salmonella typhimurium suggest that accumulation of alpha-ketobutyrate partially mediates the herbicidal activity of acetolactate synthase inhibitors. Growth inhibition of wild-type bacteria by the herbicide sulfometuron methyl was prevented by supplementing the medium with isoleucine, an allosteric inhibitor of threonine deaminase-catalyzed synthesis of alpha-ketobutyrate. In contrast, isoleucine did not rescue the growth of a mutant containing a threonine deaminase unresponsive to isoleucine. Moreover, the hypersensitivity of seven Tn10 insertion mutants to growth inhibition by sulfometuron methyl and alpha-ketobutyrate correlated with their inability to convert alpha-ketobutyrate to less noxious metabolites. We propose that alpha-ketobutyrate accumulation is an important component of sulfonylurea and imidazolinone herbicide action.
mesh_terms: D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors*; D002087:Butyrates / Q000378:metabolism*; D004251:DNA Transposable Elements; D007532:Isoleucine / Q000494:pharmacology; D007700:Kinetics; D009154:Mutation; D007652:Oxo-Acid-Lyases / Q000037:antagonists & inhibitors*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014633:Valine / Q000494:pharmacology
chemical_list: D002087:Butyrates; D004251:DNA Transposable Elements; D013453:Sulfonylurea Compounds; D007532:Isoleucine; C005087:alpha-ketobutyric acid; D000095:Acetolactate Synthase; D007652:Oxo-Acid-Lyases; D014633:Valine; C042031:sulfometuron methyl