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| | Glutamate Basic information |
| | Glutamate Chemical Properties |
| | Glutamate Usage And Synthesis |
| 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. | | Mechanism of action | The oral ingestion of Glu in protein, as the individual amino acid in the form of a dietary supplement or in the
form of the flavor enhancer monosodium glutamate (MSG), fails to significantly increase CNS levels of this
amino acid neurotransmitter. Following its ingestion, blood Glu levels do increase transiently, but largely
because of the ability of the blood-brain barrier to regulate the entry of Glu into the CNS, no significant changes
in brain Glu are observed. This ability to regulate synaptic Glu levels in brain despite fluctuations in peripheral
levels is very important, because uncontrolled variations in CNS Glu would lead to serious consequences,
ranging between seizures and coma for increases and decreases of Glu, respectively. Within the blood-brain
barrier, there exists transport proteins that are responsible for controlling the influx of amino acids into the CNS.
Of the three major types—acidic, basic, and neutral amino acid transporters—it is the acidic amino acid
transporter that carries Glu. These transporters act via facilitated diffusion and cannot operate against a
concentration gradient (active transport).
In actuality, the acidic amino acid transporter normally functions to
move Glu out of the CNS. There have been studies in which Glu, often in the form of MSG, has been injected subcutaneously to
neonatal mice or nonhuman primates and hypothalamic lesions noted. The lesions are mostly restricted to the
circumventricular organs (those near the fourth ventricle), where the blood-brain barrier is significantly
diminished. Additionally, when MSG is directly injected into the brains of laboratory animals, cellular necrosis is
observed. When MSG is given in very high doses orally, however, the homeostatic processes in liver and other tissues help to regulate plasma Glu concentrations, and large changes are not observed. Additionally, the
blood-brain barrier functions to keep CNS Glu at appropriate levels. The studies in which Glu is injected do not
reflect the chemical changes that occur following oral ingestion and should not be interpreted as an indicator of
toxicity of MSG. |
| | Glutamate Preparation Products And Raw materials |
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