Glutamate-glutamine cycle

Glutamate dehydrogenase (GDH) is an enzyme that plays a crucial role in the metabolism of amino acids. It is found in all living organisms, from bacteria to humans, and is involved in the catabolism and anabolism of glutamate, a key amino acid in cellular metabolism.

Function

Glutamate dehydrogenase catalyzes the reversible conversion of glutamate to alpha-ketoglutarate and ammonia while reducing NAD+ to NADH or NADP+ to NADPH. This reaction is a key step in the metabolism of nitrogen, allowing cells to assimilate ammonia into amino acids and other nitrogen-containing compounds.

Structure

GDH is a hexameric enzyme, meaning it is composed of six identical subunits. Each subunit contains a NAD+/NADH binding domain, a substrate binding domain, and an allosteric site. The allosteric site allows the enzyme to be regulated by various metabolites, including ADP, GTP, and leucine.

Clinical significance

Mutations in the gene encoding GDH can lead to a variety of medical conditions. For example, hyperinsulinism-hyperammonemia syndrome is caused by a gain-of-function mutation in the GDH gene, leading to excessive insulin production and elevated blood ammonia levels. On the other hand, a loss-of-function mutation in the GDH gene can cause glutamate dehydrogenase deficiency, a rare disorder characterized by developmental delay and seizures.

See also

• Amino acid metabolism
• Enzyme kinetics
• Metabolic pathway