Glutamate is a vital neurotransmitter in the central nervous system, involved in almost all significant excitatory brain functions. It is the primary and most abundant excitatory neurotransmitter, and it's estimated that over half of all neural synapses release glutamate, making it a critical player in neural circuit communication.
Glutamic acid and glutamate are essentially interchangeable terms. The two molecules are almost identical, except that glutamic acid has an additional proton, or hydrogen atom. In physiological conditions, glutamic acid sheds this extra proton and becomes glutamate, the abundant form of the amino acid in the human body.
Glutamate is a crucial excitatory neurotransmitter that plays a vital role in maintaining healthy brain and nervous system function. It enables us to learn, remember, feel, sense, and coordinate our movements effectively.
Excitatory neurotransmitters are essential in activating the next neuron in a chemical message chain, ensuring that the signal, also known as an action potential or nerve impulse, continues uninterrupted. This communication occurs through action potentials, and glutamate is one of the critical neurotransmitters that facilitate this process. Without adequate levels of glutamate, the chemical message cannot continue, and communication between neurons is disrupted.
Glutamate is also the precursor amino acid for its counterpart, the inhibitory neurotransmitter GABA (gamma-aminobutyric acid), which happens to be the most abundant amino acid in the human body. 1
Glutamate serves as an important building block for proteins in the body and is crucial for nutrition and metabolism. Additionally, it forms a crucial part of the "master antioxidant" tri-peptide glutathione as glutamic acid. The interaction between glutamate and specific taste cells in the tongue is a significant component of the umami taste experience. 2
Glutamate and GABA levels are interconnected because GABA is synthesized from glutamate with the assistance of vitamin B6. While glutamate has excitatory effects, the inhibitory effects of GABA balance them out. Glutamate increases the probability of an action potential, while GABA decreases it.
Maintaining a balance between inhibitory neuronal transmission through GABA and excitatory neuronal transmission through glutamate is crucial for maintaining cell membrane stability and optimal neurological function. This balance is necessary to ensure that our nervous system functions smoothly and effectively. 3
The glutamate-glutamine cycle is responsible for the synthesis of glutamate from glutamine. 4
In the pre-synaptic neuron, phosphate-activated glutaminase (GA) converts glutamine into glutamate, which is then stored in synaptic vesicles until it is released into the synapse.
Once glutamate is released into the synaptic cleft, it is taken up by astrocytes, a type of glial cell that provides support to the central and peripheral nervous systems.
With the help of mineral cofactors magnesium and manganese, the enzyme glutamine synthetase (GS) converts glutamate into glutamine in the astrocytes. Eventually, glutamine returns to the neuron where it is converted back into glutamate, thus restarting the cycle. 5
Glutamate, the central nervous system's most abundant and critical excitatory neurotransmitter, is widely distributed throughout the brain and spinal cord in neurons and glia and is present in more than 90% of synapses. 6
However, glutamate is also a non-essential amino acid that can be found in protein-containing foods, but its ingestion has no relationship with the glutamate circulating in the brain. This is because glutamate from high glutamate foods cannot pass through the blood-brain barrier 7 , which is a specialized system of brain microvascular endothelial cells that protects the brain from toxic substances in the blood, supplies brain tissues with nutrients, and filters harmful compounds from the brain back to the bloodstream. Instead, ingested glutamate is rapidly metabolized as oxidative fuel for the intestinal lining. 8, 26
Glutamate serves as the primary driver of neuronal excitation, playing a crucial role in a wide range of cognitive, emotional, sensory, and motor functions. Its influence extends to the activity of numerous other neurotransmitter systems, such as dopamine and serotonin. 9,10
Long-term potentiation (LTP), the primary mechanism for synaptic plasticity, is essential for learning and memory. 11, 12 Glutamate, as the primary mediator of neuronal excitation, plays a critical role in LTP. In other words, glutamate enables nerve cells to link related information, which forms the basis of memory. 9 Rather than generating new neurons to store new memories, our brain reinforces connections between existing neurons to form new memories, a process known as long-term potentiation (LTP).
- The brain can serve glutamate as a backup energy source when glucose levels are depleted.
- Glutamate levels tend to be elevated during wakefulness and the REM (rapid eye movement) phase of sleep, as noted in research. However, there is an exception to this pattern in the thalamus, where glutamate levels reach their peak during non-REM sleep. 13
- Elevated levels of glutamate in the nervous system have been linked to an escalation in the severity of pain experienced by an individual.
- Glutamate is the precursor of GABA, which is a critical inhibitory neurotransmitter that counteracts glutamate's excitatory effects.
References:
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Too much glutamate becomes excitotoxic. Excessive activation of glutamate receptors – caused by prolonged exposure to high glutamate levels – can lead to the activation of cell death pathways, resulting in excitotoxic neurodegeneration and apoptosis (aka “cell death”).14
High glutamate is associated with conditions of brain cell death or neurodegenerative diseases.
Glutamate is an amino acid. If amino acid levels are imbalanced, glutamine, glutamate, and GABA levels could be affected. Although glutamate is non-essential, meaning the body can produce glutamate from other sources, amino acid precursors such as glutamine are needed to make glutamate.
Low levels of cofactors involved in glutamate metabolism (such as magnesium, manganese, and vitamin B6) could lead to imbalanced glutamate levels.
Glutamate and glutamine are used in high quantities by the body. Illness (such as a burn) could deplete tissue levels and lead to imbalances of glutamate.
Injuries to the brain can cause an imbalance between glutamate and GABA function, resulting in excitotoxicity. 27
Neuroinflammation has also been shown to imbalance the important glutamate/GABA relationship. 28
Supplements and exercise can positively impact glutamate levels. Nutritional supplements such as vitamins B3, B6, magnesium, and manganese, amino acids, and protein may improve glutamate metabolism and balance levels. Taurine and carnitine may be beneficial in situations of glutamate excess. Pyrroloquinoline quinone (PQQ), phosphatidylserine, and docosahexaenoic acid (DHA) may provide cellular protection and balance glutamate receptor signaling. Herbal supplements, including Celastrus paniculatus, Huperzine A, Ginkgo biloba, and Rhodiola rosea, are believed to have neuroprotective effects by modulating glutamate receptor activity or decreasing glutamate-induced calcium mobilization. 18, 19, 20, 21, 22, 23, 24, 25, 29, 30
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Glutamate levels are very tightly controlled. Too little glutamate, and neural impulses will be slow, resulting in trouble concentrating and a feeling of mental exhaustion. 9
Some conditions are also believed to be associated with the brain having low glutamate levels:
Glutamate is an amino acid. If amino acid levels are imbalanced, glutamine, glutamate, and GABA levels could be affected. Although glutamate is non-essential, meaning the body can produce glutamate from other sources, amino acid precursors such as glutamine are needed to make glutamate.
Low levels of cofactors involved in glutamate metabolism (such as magnesium, manganese, and vitamin B6) could lead to imbalanced glutamate levels.
Glutamate and glutamine are used in high quantities by the body. Illness (such as a burn) could deplete tissue levels and lead to imbalances of glutamate.
Injuries to the brain can cause an imbalance between glutamate and GABA function, resulting in excitotoxicity. 27
Neuroinflammation has also been shown to imbalance the important glutamate/GABA relationship. 28
Supplements and exercise can positively impact glutamate levels. Nutritional supplements such as vitamins B3, B6, magnesium, and manganese, amino acids, and protein may improve glutamate metabolism and balance levels. Taurine and carnitine may be beneficial in situations of glutamate excess. Pyrroloquinoline quinone (PQQ), phosphatidylserine, and docosahexaenoic acid (DHA) may provide cellular protection and balance glutamate receptor signaling. Herbal supplements, including Celastrus paniculatus, Huperzine A, Ginkgo biloba, and Rhodiola rosea, are believed to have neuroprotective effects by modulating glutamate receptor activity or decreasing glutamate-induced calcium mobilization. 18, 19, 20, 21, 22, 23, 24, 25, 29, 30
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