Glutamate dehydrogenase 1, mitochondrial (GDH1)

Glutamate dehydrogenase 1 is a mitochondrial matrix enzyme encoded by the *GLUD1* gene, which catalyzes the reversible oxidative deamination of L-glutamate to α-ketoglutarate and ammonia, utilizing NAD+ or NADP+ as cofactors. It plays a critical role in nitrogen and energy metabolism, affecting glutamate flux, ammonia detoxification, and the tricarboxylic acid cycle. Allosterically regulated, GDH1 is activated by ADP and leucine and inhibited by GTP, ATP, and palmitoyl CoA. Malfunction or mutation results in metabolic diseases such as hyperinsulinism/hyperammonemia syndrome, associated with serious systemic and neurological effects. GDH1 has a hexameric structure, significant conformational flexibility, and is primarily expressed in the liver and nervous system for both metabolic and signaling functions. In research settings, polyphenolic compounds such as EGCG have been investigated as allosteric inhibitors for potential disease intervention.

Other names

Glutamate dehydrogenase 1GDH1EC 1.4.1.3mitochondrial glutamate dehydrogenaseGLUD1Glutamate dehydrogenase (NAD(P)+)Glud1 (gene symbol)

Allosteric inhibition (e.g., EGCG and other polyphenols block dysregulated GDH via binding at allosteric sites) Negative regulation by GTP, palmitoyl CoA, ATP Positive regulation by ADP, leucine