Glutamate dehydrogenase (GDH (also GLDH))

Glutamate dehydrogenase is a mitochondrial enzyme that catalyzes the reversible oxidative deamination of L-glutamate to α-ketoglutarate and ammonia, using NAD^+^ or NADP^+^ as cofactors. This reaction connects amino acid catabolism with the tricarboxylic acid cycle, making glutamate dehydrogenase a central player in both carbon and nitrogen metabolism across prokaryotes, plants, and animals[4][6][8]. In humans, it is encoded primarily by two genes—*GLUD1* and *GLUD2*. The enzyme typically forms a homohexameric structure composed of six identical subunits[9]. Glutamate dehydrogenase activity is tightly regulated allosterically. It can be inhibited by GTP, ATP, palmitoyl-CoA, Zn^2+^ ions, and EGCG; it is activated by ADP and certain amino acids such as leucine. Mutations affecting its regulatory regions can lead to diseases such as hyperinsulinism/hyperammonemia syndrome due to loss of sensitivity to inhibition by GTP[7]. In mammals—including humans—the equilibrium strongly favors glutamate oxidation rather than synthesis under physiological conditions because of low affinity for ammonia. The enzyme’s function varies among organisms. In bacteria it assimilates ammonia into amino acids; in plants it can operate bidirectionally depending on environmental conditions; in animals it mainly supports energy production from amino acids. Structural studies reveal significant conformational changes during catalysis that are essential for substrate binding and enzymatic activity[5][6]. No specific therapeutic drugs targeting glutamate dehydrogenase are currently listed in major databases based on these search results. However, its central metabolic role makes it an important target for research into metabolic disorders involving nitrogen balance or mitochondrial dysfunction. Notable safety concerns include potential toxicity from dysregulated ammonia production if GDH function becomes abnormal—a risk factor particularly relevant to inherited mutations causing hyperactivity of this enzyme[4][7].

Other names

GDHGLDHGlutamate dehydrogenase 1 (GLUD1)Glutamate dehydrogenase 2 (GLUD2)