Glutamate dehydrogenase

Definition

Glutamate dehydrogenase is an enzyme that catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate and ammonia. This reaction is crucial for integrating nitrogen metabolism and plays a key role in the citric acid cycle, linking amino acid metabolism to energy production and biosynthesis.

5 Must Know Facts For Your Next Test

1. Glutamate dehydrogenase can use either NAD+ or NADP+ as a cofactor during the reaction, which indicates its versatility in different metabolic contexts.
2. The activity of glutamate dehydrogenase is regulated by various metabolites, including ATP, ADP, and GTP, which helps to maintain the balance between energy production and consumption.
3. This enzyme plays a critical role in the urea cycle by providing ammonia for urea synthesis while also contributing to nitrogen metabolism.
4. Glutamate dehydrogenase is found in various tissues, particularly in the liver and brain, highlighting its importance in both energy metabolism and neurotransmitter function.
5. Mutations or dysregulation of glutamate dehydrogenase have been associated with metabolic disorders, including hyperinsulinism and certain neurological conditions.

Review Questions

• How does glutamate dehydrogenase contribute to the integration of amino acid metabolism with the citric acid cycle?
  • Glutamate dehydrogenase connects amino acid metabolism to the citric acid cycle by converting glutamate into alpha-ketoglutarate. This process not only provides a substrate for energy production through the citric acid cycle but also facilitates nitrogen removal from amino acids. The interconversion between glutamate and alpha-ketoglutarate allows for a seamless integration of nitrogenous compounds into central metabolic pathways.
• Discuss the regulatory mechanisms that control the activity of glutamate dehydrogenase and their significance in metabolic homeostasis.
  • The activity of glutamate dehydrogenase is tightly regulated by several metabolites such as ATP, ADP, GTP, and leucine. High levels of ATP inhibit its activity, while ADP stimulates it, reflecting the cell's energy status. This regulation ensures that the conversion of glutamate to alpha-ketoglutarate aligns with cellular energy needs and amino acid availability, maintaining metabolic homeostasis during fluctuations in nutrient supply.
• Evaluate the potential clinical implications of altered glutamate dehydrogenase activity in human health and disease.
  • Altered activity of glutamate dehydrogenase can lead to significant clinical consequences, such as hyperinsulinism due to increased ammonia production or disturbances in neurotransmitter balance affecting neurological function. Understanding these implications allows for better diagnosis and treatment strategies for metabolic disorders. Furthermore, investigating genetic mutations affecting this enzyme could provide insights into conditions like certain types of epilepsy or neurodegenerative diseases.

Related terms

Alpha-ketoglutarate: A key intermediate in the citric acid cycle, alpha-ketoglutarate is formed from the oxidative deamination of glutamate and is involved in various metabolic processes, including amino acid synthesis.

Oxidative deamination: A biochemical process where an amino group is removed from an amino acid, resulting in the formation of a corresponding keto acid and ammonia, critical for nitrogen removal in the body.

Citric acid cycle: Also known as the Krebs cycle, this series of chemical reactions takes place in the mitochondria and is essential for aerobic respiration, converting acetyl-CoA into energy-rich molecules.