AuthorGaffney, Dominique O
Jennings, Erin Q
Anderson, Colin C
Marentette, John O
Schou Oxvig, Anne-Mette
Streeter, Matthew D
Spiegel, David A
Roede, James R
Galligan, James J
AffiliationUniv Arizona, Dept Pharmacol & Toxicol, Coll Pharm
MetadataShow full item record
CitationGaffney, D. O., Jennings, E. Q., Anderson, C. C., Marentette, J. O., Shi, T., Oxvig, A. M. S., ... & Roede, J. R. (2020). Non-enzymatic lysine lactoylation of glycolytic enzymes. Cell chemical biology, 27(2), 206-213. doi:10.1016/j.chembiol.2019.11.005
JournalCELL CHEMICAL BIOLOGY
Rights© 2019 Elsevier Ltd.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractPost-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.
Note12 month embargo; published online: 22 November 2019
VersionFinal accepted manuscript
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