GLUD1

This gene encodes glutamate dehydrogenase, which is a mitochondrial matrix enzyme that catalyzes the oxidative deamination of glutamate to alpha-ketoglutarate and ammonia. This enzyme has an important role in regulating amino acid-induced insulin secretion. It is allosterically activated by ADP and inhibited by GTP and ATP. Activating mutations in this gene are a common cause of congenital hyperinsulinism. Alternative splicing of this gene results in multiple transcript variants. The related glutamate dehydrogenase 2 gene on the human X-chromosome originated from this gene via retrotransposition and encodes a soluble form of glutamate dehydrogenase. Related pseudogenes have been identified on chromosomes 10, 18 and X. [provided by RefSeq, Jan 2016]

Glutamate Dehydrogenase 1

Mitochondrial glutamate dehydrogenase that catalyzes the conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle (PubMed:11032875, PubMed:16959573, PubMed:11254391, PubMed:16023112).

Plays a role in insulin homeostasis (PubMed:9571255, PubMed:11297618).

May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity).

Glutamate biosynthetic process Source: BHF-UCL
Glutamate catabolic process Source: UniProtKB
Glutamine metabolic process Source: UniProtKB
Positive regulation of insulin secretion Source: BHF-UCL
Substantia nigra development Source: UniProtKB
Tricarboxylic acid metabolic process Source: UniProtKB

Endoplasmic reticulum; Mitochondrion. Mostly translocates into the mitochondria, only a small amount of the protein localizes to the endoplasmic reticulum.

Familial hyperinsulinemic hypoglycemia 6 (HHF6):
Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. In HHF6 elevated oxidation rate of glutamate to alpha-ketoglutarate stimulates insulin secretion in the pancreatic beta cells, while they impair detoxification of ammonium in the liver.

ADP-ribosylated by SIRT4, leading to inactivate glutamate dehydrogenase activity (PubMed:16959573). Stoichiometry shows that ADP-ribosylation occurs in one subunit per catalytically active homohexamer (PubMed:16023112).