Date published: 2025-10-11

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GLULD1 Activators

GLULD1, or Glutamate Dehydrogenase 1, is an enzyme encoded by the GLUD1 gene in humans. It plays a pivotal role in cellular metabolism by catalyzing the reversible oxidative deamination of glutamate to α-ketoglutarate and ammonia, linking amino acid metabolism to the citric acid cycle. This mitochondrial enzyme is crucial for the detoxification of ammonia in the liver and for providing the brain with glutamate, which is a key neurotransmitter and an important substrate for energy production.The activity of GLULD1 is tightly regulated by a balance of activators, which include ADP and GDP as activators, and GTP and ATP, reflecting the enzyme's role in energy metabolism and its responsiveness to the cellular energy state. This regulation ensures that GLULD1 activity is aligned with the cellular energy charge and nitrogen metabolism.

Mutations in the GLUD1 gene can lead to disorders such as hyperinsulinism-hyperammonemia syndrome, showcasing the enzyme's importance in metabolic homeostasis. GLULD1 is also implicated in the modulation of insulin secretion by the pancreas, further underscoring its role in energy metabolism.The enzyme's expression and activity are subject to change in various physiological conditions, such as diet and fasting, and in response to metabolic demands. Understanding GLULD1's function and regulation is essential for comprehending how cells manage energy and nitrogen resources, particularly in high-demand tissues like the liver and brain.

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