Glutamate dehydrogenase and transaminases (GDH/Aminotransferases)

Glutamate dehydrogenase (GDH) and transaminases (aminotransferases) represent a group of enzymes essential for the integration of nitrogen and carbon metabolism. GDH, specifically the GLUD1 and GLUD2 isoforms, catalyzes the oxidative deamination of L-glutamate to alpha-ketoglutarate, a key step in the tricarboxylic acid (TCA) cycle and ammonia production (UniProt P00367). Transaminases, including alanine transaminase (ALT) and aspartate transaminase (AST), facilitate the transfer of amino groups between amino acids and keto acids, supporting gluconeogenesis and the urea cycle (StatPearls, 2023). These enzymes are critical for regulating insulin secretion in pancreatic beta cells, where GDH activity acts as a metabolic sensor (PubMed: 11518697). Pathologically, gain-of-function mutations in GDH lead to hyperinsulinism-hyperammonemia syndrome, while elevated serum transaminases are hallmark biomarkers of liver injury and myocardial infarction (PubMed: 25611108). Pharmacological targeting of GDH is being explored in oncology, as many cancer cells exhibit 'glutamine addiction' and rely on GDH for survival (PubMed: 22457105). Inhibitors such as epigallocatechin gallate (EGCG) and various transaminase inhibitors like aminooxyacetic acid are used in research to modulate these metabolic pathways. However, therapeutic use is challenged by the systemic importance of these enzymes in maintaining nitrogen balance and liver health.

Other names

Glutamate dehydrogenaseAminotransferasesGLUD1GLUD2Alanine transaminaseAspartate transaminaseALTASTGlutamic-pyruvic transaminaseGlutamic-oxaloacetic transaminase

Inhibition of enzymatic activity to modulate nitrogen flux, reduce ammonia production, or suppress dysregulated insulin secretion.