Abstract

The tumor metabolome is characterized by high glycolytic and glutaminolytic capacities, high phosphometabolite levels and a high channelling of glucose carbons to synthetic processes. This allows tumor cells to proliferate under strong variations in oxygen and glucose supply (http://www.metabolic-database.com). One key regulator of the tumor metabolome is the glycolytic isoenzyme pyruvate kinase type M2 (M2-PK) that is generally over-expressed in all tumor cells. M2-PK can occur in a highly active tetrameric form and in a nearly inactive dimeric form. In tumor cells the dimeric form of M2-PK always predominates and has therefore been termed tumor M2-PK. The dimerization of M2-PK is caused by direct interaction of M2-PK with certain oncoproteins. When M2-PK is in its dimeric state energy is produced by glutaminolysis. The metabolic Achilles' heel of the tumor metabolome is its sensitivity to a reduction of NAD levels caused by activation of poly(ADP-ribose) polymerase after DNA damage.