The switch in glucose metabolism from oxidative phosphorylation to aerobic glycolysis by cancer cells is a key component of the Warburg effect.  A contributor to the etiology of the Warburg effect is pyruvate kinase isoform M2 (PKM2), which catalyzes the final reaction in aerobic glycolysis.  PKM2 preferentially exists as a dimer, which exhibits low affinity for its substrate, phosphoenolpyruvate (PEP).  PKM2 is highly expressed in tumor cells, which results in the accumulation of glycolytic intermediates upstream of pyruvate kinase. The intermediates are channeled into pathways that synthesize nucleic acids, phospholipids, and amino acids, resulting in increased tumor proliferation. We found that PKM2 is a protein target of HNE and ONE adduction and identified the sites of adduction by mass spectrometry. We also determined the consequences of electrophile adduction at the structural and functional level.  Adduction of PKM2 and/or electrophile-mediated crosslinking of PKM2 monomers could have significant effects on PKM2 activity.

Analysis of electrophile adduction of pyruvate kinase M2 by 4-hydroxynonenal and 4-oxononenal

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.