Glutamate dehydrogenase

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glutamate dehydrogenase 1
Identifiers
Symbol	GLUD1
Alt. Symbols	GLUD
Entrez	2746
HUGO	4335
OMIM	138130
RefSeq	NM_005271
UniProt	P00367
Other data
EC number	1.4.1.3
Locus	Chr. 10 q21.1-24.3

glutamate dehydrogenase 2
Identifiers
Symbol	GLUD2
Alt. Symbols	GLUDP1
Entrez	2747
HUGO	4336
OMIM	300144
RefSeq	NM_012084
UniProt	P49448
Other data
Locus	Chr. X q25

Glutamate dehydrogenase is an enzyme, present in mitochondria of eukaryotes, as are some of the other enzymes required for urea synthesis, that converts glutamate to α-Ketoglutarate, and vice versa.

Glutamate

Ketoglutarate

The enzyme represents a key link between catabolic and metabolic pathways, and is therefore ubiquitous in both higher and lower organisms.

Cofactors

Its cofactor for the glutamate to α-Ketoglutarate reaction, which produces ammonium as a bi-product, is NAD⁺.

Its cofactor for the reverse reaction, α-Ketoglutarate to glutamate, is NADP⁺. This reverse reaction uses ammonium to incorporate nitrogen and α-Ketoglutarate into glutamate.

Role in flow of nitrogen

Ammonia incorporation in animals occurs through the actions of glutamate dehydrogenase and glutamine synthetase. Glutamate plays the central role in mammalian nitrogen flow, serving as both a nitrogen donor and nitrogen acceptor.

Regulation of glutamate dehydrogenase

In Humans the activity of glutamate dehydrogenase is controlled through ADP-ribosilation, a covalent modification carried out by the gene sirt4. This regulation is relaxed in response to caloric restriction and low blood glucose. Under these curcumstances glutamate dehydrogenase activity is raised to increase the amount of α-Ketoglutarate that is produced. The product α-Ketoglutarate can be used to provide energy by being used in the citric acid cycle to ultimately produce ATP.

The control of GDH through ADP-ribosilation is particularly important in insulin producing β cells. Beta cells secrete insulin in response to an increase in the ATP:ADP ratio, and as amino acids are broken down by GDH into α-ketoglutarate, this ratio rises and more insulin is secreted. SIRT4 is necessary to regulate the metabolism of amino acids as a method of controlling insulin secretion and to regulate blood glucose levels.

Regulation

Allosteric inhibitors:

• Adenosine triphosphate (ATP)
• Guanosine triphosphate (GTP)

Activators:

• Adenosine diphosphate (ADP)
• Guanosine diphosphate (GDP)

See also

• Anaplerotic reactions

External links

• MeSH Glutamate+dehydrogenase

Template:1.4-enzyme-stub

v • d • e CH-NH2 oxidoreductases (EC 1.4) - primarily amino acid oxidoreductases
1.4.1 - NAD/NADP acceptor	Glutamate dehydrogenase (GLUD1)
1.4.3 - oxygen acceptor	D-amino acid oxidase - Amine oxidase - Lysyl oxidase - Monoamine oxidase
1.4.4 - disulfide acceptor	Glycine decarboxylase complex
1.4.99 - other acceptors	D-amino acid dehydrogenase - Amine dehydrogenase

v • d • e Mitochondrial enzymes and transporters
Outer membrane	Long fatty acyl CoA synthetase - Kynureninase - Monoamine oxidase
Intermembrane space	Adenylate kinase - Creatine kinase
Inner membrane	Coenzyme Q - cytochrome c reductase -Cytochrome c - Dihydroorotate dehydrogenase -Glutamate aspartate transporter - Glycerol-3-phosphate dehydrogenase - NADH dehydrogenase - Succinate dehydrogenase
Matrix	Aconitase - Aspartate transaminase - ALDH2 - Carbamoyl phosphate synthase - Citrate synthase - Fumarase - Glutamate dehydrogenase - Isocitrate dehydrogenase - Malate dehydrogenase - Ornithine transcarbamoylase - Oxoglutarate dehydrogenase - Pyruvate dehydrogenase complex - Succinyl coenzyme A synthetase
Mitochondrial DNA	Complex I (7 units) - Complex III (1 unit) - Complex IV (3 units) - ATP synthase (2 units)

v • d • e Metabolism: Citric acid cycle enzymes
Cycle	Citrate synthase - Aconitase - Isocitrate dehydrogenase - Oxoglutarate dehydrogenase - Succinyl CoA synthetase Succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD) - Fumarase - Malate dehydrogenase
Anaplerotic	to acetyl-CoA: Pyruvate dehydrogenase complex (regulated by Pyruvate dehydrogenase kinase and Pyruvate dehydrogenase phosphatase) to ketoglutaric acid: Glutamate dehydrogenase to succinyl-CoA: Methylmalonyl-CoA mutase to oxaloacetate: Pyruvate carboxylase - Aspartate transaminase

bg:Глутаматдехидрогеназа

de:Glutamatdehydrogenase nl:Glutamaat-dehydrogenase