The tumor metabolome.
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.
Mazurek
Sybille
S
Institute for Biochemistry and Endocrinology, Veterinary Faculty, Justus-Liebig-University of Giessen, Frankfurter Strasse 100, 35392 Giessen, Germany.
Eigenbrodt
Erich
E
D015894:Genome, Human; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D011770:Pyruvate Kinase / Q000378:metabolism
D007527:Isoenzymes; D005973:Glutamine; D011770:Pyruvate Kinase; D005947:Glucose