Glutamate

Description

The major EAA neurotransmitter in the CNS is L-Glu. (Note that all amino acids with the exception of glycine mentioned in this chapter are considered to be in the “L” configuration; thus, the “L” will be omitted, unless specifically indicated as “D” ). Early studies in invertebrates demonstrated the potent actions of the acidic amino acid Glu, as well as another acidic amino acid, Asp. Acceptance of Glu as a neurotransmitter in the CNS was delayed for many years as neuroscientists attempted to distinguish its role as a component of protein and peptides (e.g., glutathione), an important intermediate in numerous metabolic processes, and as a precursor to the inhibitory neurotransmitter GABA. Whereas Glu is found in all cells within the CNS, an unequal distribution of this amino acid as well as of Asp has been demonstrated.
Glutamate is synthesized in the CNS via the transamination of α-ketoglutarate, which is produced from glucose in the Krebs cycle. Additionally, Glu can be synthesized from glutamine via glutaminase. Once produced, Glu can be stored in vesicles. With the vast number of compounds that can feed into the Krebs cycle and the various sources of glucose, it is not surprising that the control of Glu synthesis in the CNS is still poorly understood.