title: Suicide inhibition of acetohydroxyacid synthase by hydroxypyruvate.
abstract: Acetohydroxyacid synthase (Ec 2.2.1.6) catalyses the thiamine diphosphate-dependent reaction between two molecules of pyruvate yielding 2-acetolactacte and CO2. The enzyme will also utilise hydroxypyruvate with a k(cat) value that is 12% of that observed with pyruvate. When hydroxypyruvate is the substrate, the enzyme undergoes progressive inactivation with kinetics that are characteristic of suicide inhibition. It is proposed that the dihydroxyethyl-thiamine diphosphate intermediate can expel a hydroxide ion forming an enol that rearranges to a bound acetyl group.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Queensland, Brisbane, Qld 4072, Australia. ronald.duggleby@uq.edu.au
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Duggleby
mesh_terms: D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002384:Catalysis; D004926:Escherichia coli / Q000201:enzymology; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D007700:Kinetics; D011773:Pyruvates / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013379:Substrate Specificity; D013835:Thiamine Pyrophosphate / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D011773:Pyruvates; D011994:Recombinant Proteins; C093420:dihydroxyethylthiamine pyrophosphate; D005182:Flavin-Adenine Dinucleotide; C012375:hydroxypyruvic acid; D000095:Acetolactate Synthase; D013835:Thiamine Pyrophosphate