Glutamate

Glutamate, also known as L-glutamic acid when in free form, is one of the 20 standard amino acids used to build proteins. At physiological pH it exists mainly as the anion glutamate and serves as a key metabolite in cellular energy production, nitrogen balance, and amino acid biosynthesis. In humans, most glutamate is incorporated into proteins, while small amounts exist as a free amino acid in tissues and in the central nervous system.

In the brain, L-glutamate is the principal excitatory neurotransmitter. It is released from presynaptic terminals and activates ionotropic receptors—NMDA, AMPA, and kainate—as well as metabotropic glutamate receptors. Activation of these receptors triggers depolarization and intracellular signaling that underlies synaptic plasticity, learning, and memory. Glutamate signaling is tightly regulated by transporters that remove neurotransmitter from the synaptic cleft, primarily excitatory amino acid transporters (EAATs) on neurons and astrocytes.

After release, glutamate is cleared and can be converted to glutamine in astrocytes by glutamine synthetase, forming part of the glutamate–glutamine cycle that shuttles nitrogen and neurotransmitter between glia and neurons. Glutamate is also transaminated to produce alpha-ketoglutarate, entering the tricarboxylic acid cycle.

Excessive glutamate exposure can cause excitotoxicity, contributing to neuronal injury in conditions such as stroke and neurodegenerative diseases. Dietary glutamate occurs naturally in protein-rich foods and is also added as monosodium glutamate (MSG) to some foods as a flavor enhancer. Regulatory agencies consider MSG safe for the general population; claims of adverse reactions lack consistent scientific evidence, though a small subset of individuals report sensitivity.