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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. The produced ammonia is, however, usually bled off to the urea cycle.
The enzyme represents a key link between catabolic and metabolic pathways, and is therefore ubiquitous in eukaryotes.
[edit] Cofactors
Its cofactor for the glutamate to α-Ketoglutarate reaction, which produces ammonium as a byproduct, is NAD+(or NADP+).
[edit] 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.
[edit] Regulation of glutamate dehydrogenase
In Humans the activity of glutamate dehydrogenase is controlled through ADP-ribosylation, a covalent modification carried out by the gene sirt4. This regulation is relaxed in response to caloric restriction and low blood glucose. Under these circumstances 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-ribosylation 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.
[edit] Regulation
Allosteric inhibitors:
Activators:
[edit] See also
[edit] External links
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Mitochondrial enzymes and transporters |
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| Outer membrane |
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| Intermembrane space |
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| Inner membrane |
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| Matrix |
citric acid cycle ( Citrate synthase, Aconitase, Isocitrate dehydrogenase, Oxoglutarate dehydrogenase, Succinyl coenzyme A synthetase, Fumarase, Malate dehydrogenase)
anaplerotic reactions (Aspartate transaminase, Glutamate dehydrogenase, Pyruvate dehydrogenase complex)
urea cycle (Carbamoyl phosphate synthetase I, Ornithine transcarbamylase, N-Acetylglutamate synthase)
alcohol metabolism ( ALDH2)
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| Mitochondrial DNA |
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