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Glutamate plays an especially important role in clinical neurology because elevated concentrations of extracellular glutamate, released as a result of neural injury, are toxic to neurons. Free glutamic acid cannot cross the blood-brain barrier in the needed quantities but is instead converted into L-glutamine. The brain uses L-glutamine for fuel and protein synthesis. Glutamate is involved in cognitive functions like learning and memory in the brain. The neurotransmitter L-glutamate functions as an excitatory neurotransmitter and is a precursor for the synthesis of gamma-aminobutyric acid or γ-aminobutyric acid (GABA) in GABAergic neurons. GABAergic neurons transmit or secret γ-aminobutyric acid. L-Glutamate is also considered to be nature's "Brain food." L-glutamate helps to improve the mental capacities in humans and to speed up the healing of ulcers. In addition, L-glutamate has been reported to help control alcoholism, schizophrenia and the craving for sugar. However, excessive amounts of L-glutamate may cause neuronal damage and are associated with diseases such as amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease. Glutamate activates both ionotropic and metabotropic glutamate receptors. Ionotropic and metabotropic receptors are both ligand gated transmembrane proteins. Ionotropic receptors change shape when they are bound by a ligand. This change in shape creates a channel that allows ions to flow through. On the other hand, metabotropic receptors do not have channels and activate a G-protein that in turn activates a secondary messenger that may then activate a "secondary effector" whose effects depend on the particular secondary messenger system.
Glutamate can cause neuronal damage and eventual cell death, particularly when N-Methyl-D-aspartic acid or N-Methyl-D-aspartate (NMDA) receptors are activated. High dosages of glutamic acid may induce symptoms such as headaches and neurological problems. The pathological process called excitotoxicity damages and kills nerve cells. This is caused via excessive stimulation by neurotransmitters such as glutamate and similar substances. Unfortunately, glutamate is of transient nature in biological systems and is therefore extremely difficult to study in action. However, quantitative amino acid analysis can be used to determine the presence of L-glutamate in different tissue types, plasma and other bodily fluids including dietary supplements and foods.
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