Home > A. Molecular pathology > glutamate

glutamate

Monday 3 May 2004

Glutamate is a central junction for interchange of amino nitrogen, glutamate facilitates both amino acid synthesis and degradation.

- In the liver, glutamate is the terminus for release of ammonia from amino acids, and the intrahepatic concentration of glutamate modulates the rate of ammonia detoxification into urea.
- In pancreatic beta-cells, oxidation of glutamate mediates amino acid-stimulated insulin secretion.
- In the central nervous system, glutamate serves as an excitatory neurotransmittor.

  • L-glutamate is the major excitatory neurotransmitter in the brain and is responsible for normal brain function. High glutamate exposure triggers neuronal death, a process known as excitotoxicity. Excitotoxicity is associated with acute and chronic neurodegenerative diseases.
  • Excessive glutamate signaling can lead to excitotoxicity, a phenomenon whereby over-activation of glutamate receptors initiates neuronal death. Glutamate can be toxic to white-matter oligodendrocytes.

- Glutamate is also the precursor of the inhibitory neurotransmittor GABA, as well as glutamine, a potential mediator of hyperammonemic neurotoxicity.

Pathology (Disorders of glutamate metabolism)

- mutations of the glutamate dehydrogenase in a form of congenital hyperinsulinism associated with asymptomatic hyperammonemia

- disruptions of glutamate metabolism

  • pyridoxine-dependent seizures

- missense mutation in the gene encoding one of the two mitochondrial glutamate/H(+) symporters in autosomal recessive neonatal myoclonic epilepsy (15592994)

See also

- glutamate oxidation
- glutamate receptors
- glutamate excitotoxicity
- glutamate synapse

References

- Nicholls DG. Mitochondrial dysfunction and glutamate excitotoxicity studied in primary neuronal cultures. Curr Mol Med. 2004 Mar;4(2):149-77. PMID: 15032711

- Aarts MM, Tymianski M. Molecular mechanisms underlying specificity of excitotoxic signaling in neurons. Curr Mol Med. 2004 Mar;4(2):137-47. PMID: 15032710

- Tanaka K. Antibiotics rescue neurons from glutamate attack. Trends Mol Med. 2005 Jun;11(6):259-62. PMID: 15949765

- Kelly A, Li C, Gao Z, Stanley CA, Matschinsky FM. Glutaminolysis and insulin secretion: from bedside to bench and back. Diabetes. 2002 Dec;51 Suppl 3:S421-6. PMID: 12475785

- Nedergaard M, Takano T, Hansen AJ. Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci. 2002 Sep;3(9):748-55. PMID: 12209123

- Kelly A, Stanley CA. Disorders of glutamate metabolism. Ment Retard Dev Disabil Res Rev. 2001;7(4):287-95. PMID: 11754524

Portfolio

  • Glutamate and cerebral ammonia detoxification