Glutamate dehydrogenase (GDH) is an enzyme that plays a central role in amino acid metabolism. It catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate and ammonia, linking amino acid metabolism with the tricarboxylic acid (TCA) cycle.
Role of GDH in Metabolism
• GDH converts glutamate, a key amino acid, into α-ketoglutarate, which is an essential intermediate in the TCA cycle.
• By doing so, GDH contributes to energy production and anaplerosis (replenishment of TCA cycle intermediates).
•GDH activity can support cell survival when cancer cells rely not only on glycolysis (the Warburg effect) but also on glutaminolysis—using glutamine as a key nutrient for energy and biosynthesis.
GDH Expression in Cancer
• Many cancers exhibit metabolic reprogramming to support rapid growth and proliferation. Some tumors have been found to upregulate GDH expression, allowing them to better use glutamine and glutamate as alternative energy sources.
• Elevated GDH expression can facilitate increased flux of glutamate into the TCA cycle, thereby supporting bioenergetic and biosynthetic demands of cancer cells.
• The increase in GDH activity may also help cancer cells adapt to nutrient-depleted or hypoxic microenvironments by offering metabolic flexibility.
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