Glutamate dehydrogenase 2, mitochondrial (GLUD2)

Glutamate dehydrogenase 2, mitochondrial (GLUD2), is a mitochondrial enzyme encoded by the X-linked GLUD2 gene, specific to humans and great apes. It catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate and ammonia, playing a critical role in glutamate recycling during neurotransmission in the brain and in testis. GLUD2 arose via retroposition of the GLUD1 gene and has unique regulatory features: it is largely regulated by ADP and L-leucine, and is insensitive or less sensitive to GTP inhibition relative to GLUD1. Distinct biochemical and regulatory properties enable GLUD2 to support metabolic requirements during early brain development, particularly related to lipid biosynthesis and neuronal growth, rather than direct neurotransmitter cycling. Disease-associated gain-of-function variants in GLUD2, such as Ala445, increase enzyme activity and can promote earlier onset of neurodegenerative diseases, such as Parkinson’s disease, likely through excessive glutamate dehydrogenation and increased vulnerability of dopaminergic neurons. GLUD2 is mainly expressed in neural and testicular tissues and, due to its role in nitrogen and energy metabolism, is implicated in metabolic and neurodegenerative disorders[1][2][3][4][5][6].

Other names

GLUD2GDH2GLUDP1DHE4glutamate dehydrogenase 2, mitochondrialtesticular secretory protein Li 14glutamate dehydrogenase pseudogene 1

Allosteric regulation by ADP and L-leucine (activation) - Inhibition by GTP (wild type; some mutants are resistant) - Sensitivity to inhibition by estrogens (certain polymorphisms)[3][1].