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Glutamate

Explanations > Brain stuff > Brain chemistry > Neurotransmitters > Glutamate

Composition | Function | Dysfunction | See also

Glutamate, or glutamic acid is the most common neurotransmitter in all mammals.

Composition

Chemically, glutamate is an amino acid and is an essential molecule in general cell metabolism. Proteins are broken down by digestion into amino acids.

Glutamate binds to receptors including the NMDA (N-methyl, D-aspartate) receptor, (or NMDAR). This receptor has six binding sites, two within the ion channel. It passes both Na⁺ and Ca²⁺ ions, which will cause depolarization. Calcium also acts as a second messenger, binding and activating various enzymes.

The AMPA receptor is most common and controls a sodium channel and is stimulated by AMPA. The kainate receptor is stimulated by kainic acid and controls a sodium channel. All of these are ionotropic. The metabotropic glubamate receptor is, unsurprisingly, metabotropic. It also has eight subtypes.

Glutamate receptors may need additional molecules to bind to open, eg. NMDA also need glycine. Further, for the calcium channel to open, a magnesium Mg²⁺ ion must not be attached, although a partically depolarized postsynaptic membrane will release magnesium ions. In other words, NMDA opens only if glutamate is present and the postsynaptic membrane is depolarized. NMDA also has a Zn²⁺ binding site, which decreases the effect, and a polyamide site which facilitates operation.

Function

Glutamate appears in simple organisms and is thought to be the first neurotransmitters to evolve.

Calcium flow through NMDARs is thought to play a key role in synaptic plasticity and hence affects learning and memory. They also have generic and non-specific activation functions. NMDA antagonists act as anaesthetics and hallucinogenics.

Glutamate is a precursor to the neurotransmitter GABA.

Note: aspartate also binds to NMDARs but does not stimulate them as strongly.

Dysfunction

Excitotoxicity due to glutamate is associated with stroke, autism, mental retardation and Alzheimer's disease.

Drugs

2-amino-5-phosphonopentanoate (AP5) blocks glutamate binding at NMDA receptors, impairing learning.

Phenylcyclidine (PCP or 'angel dust') binds to a special NMDA site where it acts as an indirect antagonist. It has been used as an anesthetic but has intoxicating effects that can include hallucinations, 'out of body' experience and euphoria. It can create schizophrenic symptom and may cause damage called Olney's lesions.

N-methyl-D-aspartic acid (NMDA) is a direct agonist for the NMDA receptor

alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) is a direct agonist for the AMPA receptor and generates fast Excitatory postsynaptic potential.

Kainic acid (kainate) is is a direct agonist for the Kainate receptor and is a potential CNS stimulant.