Glutamate dehydrogenase 1 (GLUD1) (GLUD1)

Glutamate dehydrogenase 1 (GLUD1) is a mitochondrial enzyme that plays a pivotal role in cellular metabolism by catalyzing the reversible oxidative deamination of L-glutamate to alpha-ketoglutarate and ammonia, using NAD+ or NADP+ as cofactors [UniProt]. It serves as a critical bridge between amino acid catabolism and the tricarboxylic acid (TCA) cycle, thereby regulating energy production and nitrogen balance [PubMed]. In humans, GLUD1 is subject to complex allosteric regulation, being activated by ADP and inhibited by GTP and NADH, which allows the enzyme to sense and respond to the energy status of the cell [NCBI]. Dysregulation of this enzyme, particularly through gain-of-function mutations, is the primary cause of Hyperinsulinism-hyperammonemia syndrome (HI/HA), characterized by inappropriate insulin secretion and elevated blood ammonia [StatPearls]. Furthermore, GLUD1 is frequently upregulated in various cancers to facilitate glutaminolysis, providing essential metabolic intermediates for rapid tumor proliferation [PubMed]. Consequently, GLUD1 is an emerging therapeutic target for metabolic disorders and oncology, with allosteric inhibitors like epigallocatechin gallate (EGCG) being studied for their potential to disrupt these pathological pathways [PubChem]. Bovine liver glutamate dehydrogenase is historically significant as the primary biochemical model for studying these regulatory mechanisms due to its high sequence homology and structural similarity to the human enzyme [PubMed].

Other names

Bovine liver glutamate dehydrogenaseGDHGLUDGlutamate dehydrogenase (NAD(P)+)GDH1

Allosteric modulation of the enzyme's catalytic activity by binding to regulatory sites (such as the antenna or pivot regions), which stabilizes the enzyme in either an active or inactive conformation to control the flux of glutamate into the TCA cycle [PubMed].