Glutamate
Overview
Glutamate is an amino acid that plays a key role in cellular metabolism. It is the most abundant excitatory neurotransmitter in the vertebrate nervous system and is involved in a variety of metabolic pathways. Glutamate is also a building block for protein synthesis and is involved in the regulation of synaptic plasticity, which is important for learning and memory.
Structure and Properties
Glutamate is a non-essential amino acid with a linear structure. It is a polar, acidic amino acid due to the presence of a second carboxyl group in its side chain. This carboxyl group can lose a proton, resulting in a negatively charged carboxylate ion, which gives glutamate its acidic properties.
Biosynthesis
Glutamate is synthesized in cells by a process known as transamination. This process involves the transfer of an amino group from a donor molecule, usually another amino acid, to a recipient molecule, usually a keto acid. The enzyme that catalyzes this reaction is called glutamate dehydrogenase.
Role in Metabolism
Glutamate plays a central role in nitrogen metabolism. It serves as a nitrogen donor in the synthesis of other amino acids, nucleotides, and other nitrogen-containing compounds. Glutamate is also a key intermediate in the citric acid cycle, where it can be converted into alpha-ketoglutarate, a key intermediate in the cycle.
Role in Neurotransmission
In the nervous system, glutamate acts as an excitatory neurotransmitter. It is released from nerve terminals in response to an action potential and binds to glutamate receptors on the postsynaptic neuron. This binding triggers an influx of positive ions into the neuron, leading to depolarization and the generation of an action potential.
Glutamate Receptors
There are two main types of glutamate receptors: ionotropic and metabotropic. Ionotropic glutamate receptors are ligand-gated ion channels that allow the flow of ions across the cell membrane when glutamate binds. Metabotropic glutamate receptors, on the other hand, are G protein-coupled receptors that activate intracellular signaling pathways when glutamate binds.
Role in Disease
Abnormal glutamate signaling has been implicated in a number of neurological and psychiatric disorders, including epilepsy, Alzheimer's disease, Parkinson's disease, and schizophrenia. In many of these conditions, there is evidence of glutamate excitotoxicity, a process in which excessive glutamate signaling leads to neuronal damage and death.