GLUD1 Human

GLUD1 catalyzes the oxidative deamination of L-glutamate to 2-oxoglutarate and ammonia, using NAD+ or NADP+ as a cofactor . This reaction is reversible and is central to the metabolism of glutamate, an important neurotransmitter in the brain . The enzyme is composed of six identical subunits and is regulated by various allosteric effectors, including ADP (activator) and GTP/ATP (inhibitors) .

GLUD1 is expressed at high levels in the liver, brain, pancreas, and kidney, but not in muscle . In the nervous tissue, it functions in both the synthesis and catabolism of glutamate and may play a role in ammonia detoxification . The regulation of GLUD1 is complex and involves multiple substrate and regulatory binding sites .

Mutations in the GLUD1 gene can lead to hyperinsulinism-hyperammonemia syndrome, a condition characterized by excessive insulin and ammonia levels in the blood . Additionally, GLUD1 has been implicated in various cancers, including breast cancer, where it plays a role in ammonia assimilation and tumor proliferation .

Recombinant human GLUD1 is often produced in E. coli and is used in various research applications, including studies on enzyme kinetics, regulation, and structure . The recombinant protein typically includes an N-terminal His-tag for purification purposes and is used in assays such as Western Blotting and imaging .

There are two paralogs of glutamate dehydrogenase in humans, GLUD1 and GLUD2, which arose from a recent retroposition event during primate evolution . These paralogs have different regulatory properties and are not fully characterized at the structural level .