Physiological Role of Glutamate Dehydrogenase in Cancer Cells

increased growth rates and final densities of several human metastatic cancer cells. To assess whether glutamate dehydrogenase (GDH) in cancer cells may catalyze the reverse reaction of fixation, its covalent regulation and kinetic parameters were determined under near-physiological conditions. Increased total protein and phosphorylation were attained in -supplemented metastatic cells, but total cell GDH activity was unchanged. Higher values for the GDH reverse reaction vs. forward reaction in both isolated hepatoma (HepM) and liver mitochondria [rat liver mitochondria (RLM)] favored an -fixing role. GDH sigmoidal kinetics with , ADP, and leucine fitted to Hill equation showed values of 2 to 3. However, the values for were over 20 mM, questioning the physiological relevance of the GDH reverse reaction, because intracellular in tumors is 1 to 5 mM. In contrast, data fitting to the Monod-Wyman-Changeux (MWC) model revealed lower values for , of 6 to 12 mM. analysis made with MWC equation, and using physiological concentrations of substrates and modulators, predicted GDH N-fixing activity in cancer cells. Therefore, together with its thermodynamic feasibility, GDH may reach rates for its reverse, -fixing reaction that are compatible with an anabolic role for supporting growth of cancer cells.