甲基乙二醛
酶
赖氨酸
乳糖谷胱甘肽裂解酶
糖酵解
生物化学
谷胱甘肽
化学
焊剂(冶金)
代谢物
生物
氨基酸
有机化学
作者
Dominique O. Gaffney,Erin Q. Jennings,Colin C. Anderson,John Marentette,Taoda Shi,Anne Mette Schou Oxvig,Matthew D. Streeter,Mogens Johannsen,David A. Spiegel,Eli Chapman,James R. Roede,James J. Galligan
标识
DOI:10.1016/j.chembiol.2019.11.005
摘要
Post-translational modifications (PTMs) regulate enzyme structure and function to expand the functional proteome. Many of these PTMs are derived from cellular metabolites and serve as feedback and feedforward mechanisms of regulation. We have identified a PTM that is derived from the glycolytic by-product, methylglyoxal. This reactive metabolite is rapidly conjugated to glutathione via glyoxalase 1, generating lactoylglutathione (LGSH). LGSH is hydrolyzed by glyoxalase 2 (GLO2), cycling glutathione and generating D-lactate. We have identified the non-enzymatic acyl transfer of the lactate moiety from LGSH to protein Lys residues, generating a "LactoylLys" modification on proteins. GLO2 knockout cells have elevated LGSH and a consequent marked increase in LactoylLys. Using an alkyne-tagged methylglyoxal analog, we show that these modifications are enriched on glycolytic enzymes and regulate glycolysis. Collectively, these data suggest a previously unexplored feedback mechanism that may serve to regulate glycolytic flux under hyperglycemic or Warburg-like conditions.
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