Suicide inhibition of acetohydroxyacid synthase by hydroxypyruvate

Ronald G. Duggleby
2005 Journal of Enzyme Inhibition and Medicinal Chemistry  
Acetohydroxyacid synthase (Ec 2.2.1.6) catalyses the thiamine diphosphate-dependent reaction between two molecules of pyruvate yielding 2-acetolactacte and CO 2 . 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
more » ... ermediate can expel a hydroxide ion forming an enol that rearranges to a bound acetyl group.
doi:10.1080/14756360400020553 pmid:15895677 fatcat:xekwvqqhfbek5hrkt4bxscoqda