GABA and glutamate in the human brain.

21.07.1989 · Transmitter glutamate released from glutamatergic n ..

01.11.2017 · GABA and glutamate in the human brain

GABA and glutamine are both available over the counter in health food stores. Glutamine is usually found labeled "l-glutamine". (The "l-" stands for the direction the molecule "turns". All amino acids are either "d-" or "l-", but the body only accepts and works with molecules spun in the "l-" direction.)

which can be recycled through the tricarboxylic acid cycle to synthesize glutamate

Animation 6.2: Neurotransmitter Pathways: Glutamate ..

illustrates an alternative model for aspartate-dependent glutamate/glutamine synthesis with four critical properties: (1) it satisfies the experimental observations made by Pardo et al without requiring extracellular trafficking of aspartate; (2) it explains why the provision of aspartate would stimulate astrocytic glutamate/glutamine synthesis; (3) it shows that astrocytes can form aspartate from acetate in aralar−/− animals, but are unable to transfer this aspartate to the astrocytic cytosol in the absence of aralar; and (4) it fulfills the important criterion that all transport processes across the mitochondrial membranes are stoichiometrically balanced. The figure shows that α-ketoglutarate, which was synthesized in the astrocytic TCA cycle—as in the Pardo model—is carried to the cytosol by OGC in exchange with malate, and transaminated to glutamate, and that a need is created for cytosolic aspartate (pathway 1). The generated glutamate is amidated with NH4+ to glutamine, which is transferred to neurons, where it is released as the transmitter glutamate (pathway 2). To simplify matters, the conversion of glutamine to transmitter glutamate in neurons by phosphate-activated glutaminase is indicated as entirely occurring in the cytosol, but it makes no difference for astrocytic reactions whether this is the case, or glutamate has to enter the mitochondria as described by .

Brain glutamine synthesis requires neuronal aspartate: …

by Niels Chr. Danbolt

For more references and more information, see: :
Prog. Neurobiol. 65, 1-105.

Glutamate

Outside the community of biomedical scientists, glutamate is probably best known as "monosodium glutamate" or "MSG" which is used as a flavor or taste enhancer in food. It is usually available together with other food additives and spices in most large food stores. Some people may also have heard the term "Chinese restaurant syndrome" which is a sudden fall in blood pressure with subsequent fainting after ingestion of very spicy food. Excessive use of MSG has been suggested to be the cause, but this is controversial. The use of glutamate as a food additive, however, is not the reason for the enormous scientific interest in glutamate.


Brain Glutamine Synthesis Requires Neuronal-Born …

The concentration of glutamate in the brain extracellular fluid must be kept low (~3 μM) in order to maximize the signal-to-noise ratio upon the release of glutamate from neurons. In addition, the nerve endings require a supply of glutamate precursors that will not cause depolarization. The major precursor to neuronal glutamate is glutamine, which is synthesized in astrocytes and converted to glutamate in neurons. However, glutamine is not the sole source. Alanine also might serve as a precursor to glutamate via transamination, although this reaction is relatively inactive in synaptosomes. Finally, the branched-chain amino acids, and in particular leucine, appear to be very important precursors to glutamate and glutamine in astrocytes. By providing α-NH2 groups for the synthesis of glutamine, leucine also abets the uptake into brain of neutral amino acids, which are transported in exchange for brain glutamine. In addition, the branched-chain ketoacids are readily reaminated to the cognate amino acids, in the process consuming glutamate. Intraneuronal consumption of glutamate via ketoacid reamination might serve to buffer internal [glutamate] and to modulate the releasable pool.

Glutamate as a Neurotransmitter in the Brain: Review …

The glutamate transporters remove glutamate from the extracellular fluid
It follows from the description above that the mechanisms which can maintain low extracellular concentrations of glutamate are essential for brain function. The only (significant) mechanism for removal of glutamate from the extracellular fluid is cellular uptake of glutamate; the so called “glutamate uptake”. This uptake is mediated by a family of special transporter proteins which act as pumps. These proteins bind glutamate, one molecule at the time, and transfer them into the cells. In agreement with the abundance of glutamate and the ubiquity of glutamate receptors, brain tissue displays a very high glutamate uptake activity. This was noted already in 1949, although its true importance was not recognized until after the excitatory action of glutamate was discovered in the 1950s and 1960s.

Glutamate is taken up into both glial cells and nerve terminals. The former is believed to be the more important from a quantitative point of view. Glutamate taken up by astroglial cells is converted to glutamine. Glutamine is inactive in the sense that it cannot activate glutamate receptors, and is released from the glial cells into to extracellular fluid. Nerve terminals take up glutamine and convert glutamine back to glutamate. This process is referred to as the glutamate-glutamine, and is important because it allows glutamate to be inactivated by glial cells and transported back to neurons in an inactive (non-toxic) form.


and three neuronal transporters in the brain

N2 - The concentration of glutamate in the brain extracellular fluid must be kept low (~3 μM) in order to maximize the signal-to-noise ratio upon the release of glutamate from neurons. In addition, the nerve endings require a supply of glutamate precursors that will not cause depolarization. The major precursor to neuronal glutamate is glutamine, which is synthesized in astrocytes and converted to glutamate in neurons. However, glutamine is not the sole source. Alanine also might serve as a precursor to glutamate via transamination, although this reaction is relatively inactive in synaptosomes. Finally, the branched-chain amino acids, and in particular leucine, appear to be very important precursors to glutamate and glutamine in astrocytes. By providing α-NH2 groups for the synthesis of glutamine, leucine also abets the uptake into brain of neutral amino acids, which are transported in exchange for brain glutamine. In addition, the branched-chain ketoacids are readily reaminated to the cognate amino acids, in the process consuming glutamate. Intraneuronal consumption of glutamate via ketoacid reamination might serve to buffer internal [glutamate] and to modulate the releasable pool.