GLUTAMATE (NEUROTRANSMITTER): SYNTHESIS, ACTION, FUNCTIONS - NEUROPSYCHOLOGY - 2024

The glutamate is the most abundant excitatory neurotransmitter in the nervous system function in vertebrate organisms. It plays a fundamental role in all excitatory functions, which implies that it is related to more than 90% of all synaptic connections in the human brain.

Biochemical glutamate receptors can be divided into three classes: AMPA receptors, NMDA receptors, and metabotropic glutamate receptors. Some experts identify a fourth type, known as kainate receptors. They are found in all brain regions, but are especially abundant in some areas.

Source: pixabay.com

Glutamate plays a fundamental role in synaptic plasticity. Because of this, it is especially related to certain advanced cognitive functions such as memory and learning. A specific form of plasticity, known as long-term potentiation, occurs at glutamatergic synapses in areas such as the hippocampus or the cortex.

In addition to all this, glutamate also has a number of health benefits when consumed through diet in moderation. However, it can also cause some negative effects if you concentrate too much, both brain level and in food. In this article we will tell you everything about him.

Synthesis

Structure of L-Glutamate

Glutamate is one of the main components of a large number of proteins. Because of this, it is one of the most abundant amino acids in the entire human body. Under normal circumstances, it is possible to obtain enough of this neurotransmitter through diet, so that it is not necessary to synthesize it.

However, glutamate is considered a non-essential amino acid. This means that, in times of emergency, the body can metabolize it from other substances. Specifically, it can be synthesized from alpha-Ketoglutaric acid, which is produced by the citric acid cycle from citrate.

At the brain level, glutamate is not capable of crossing the blood-brain barrier by itself. However, it moves through the central nervous system using a high-affinity transport system. This serves to regulate its concentration and keep the amount of this substance found in brain fluids constant.

In the central nervous system, glutamate is synthesized from glutamine in a process known as the "glutamate-glutaminergic cycle", through the action of the enzyme glutaminase. This can occur both in presynaptic neurons and in the glial cells that surround them.

On the other hand, glutamate is itself a precursor to another very important neurotransmitter, GABA. The transformation process is carried out by the action of the glutamate decarboxylase enzyme.

Mechanism of action

The AMPA receptor binds to an L-glutamate antagonist showing the amino terminal, ligand-binding domain, and transmembrane domain, PDB 3KG2. Curtis Neveu Glutamate exerts its effect on the body by binding to four different types of biochemical receptors: AMPA receptors, NMDA receptors, metabotropic glutamate receptors, and kainate receptors. Most of them are located within the central nervous system.

In fact, the vast majority of glutamate receptors are located on the dendrites of postsynaptic cells; and they bind to molecules released into the intra-synaptic space by presynaptic cells. On the other hand, they are also present in cells such as astrocytes and oligodendrocytes.

Glutamine receptors can be divided into two subtypes: ionotropic and metabotropic. Below we will see how each of them works in more detail.

Ionotropic receptors

Ionotropic receptor.

The ionotropic glutamate receptors have the primary function of allowing sodium, potassium, and sometimes calcium ions to pass through the brain in response to glutamate binding. When binding occurs, the antagonist stimulates the direct action of the receptor's central pore, an ion channel, thus allowing the passage of these substances.

The passage of sodium, potassium and calcium ions causes a postsynaptic excitatory current. This current is depolarizing; and if a sufficient number of glutamate receptors are activated, the action potential in the postsynaptic neuron can be reached.

All types of glutamate receptors are capable of producing a postsynaptic excitatory current. However, the speed and duration of this current is different for each of them. Thus, each of them has different effects on the nervous system.

Metabotropic receptors

Metabotropic glutamate receptors belong to the C subfamily of G protein receptors. They are divided into three groups, which in turn are divided into eight subtypes in the case of mammals.

These receptors are made up of three distinct parts: the extracellular region, the transmembrane region, and the intracellular region. Depending on where the bond with the glutamate molecules occurs, a different effect will occur in the body or in the nervous system.

The extracellular region is made up of a module known as the "Venus flytrap" that is responsible for binding glutamate. It also has a part rich in cysteine ​​that plays a fundamental role in the transmission of the change of current towards the part of the transmembrane.

The transmembrane region is made up of seven areas, and its main function is to connect the extracellular zone with the intracellular zone, where protein coupling generally occurs.

The binding of glutamate molecules in the extracellular region causes the proteins that reach the intracellular region to be phosphorylated. This affects a large number of biochemical pathways and ion channels in the cell. Because of this, metabotropic receptors can cause a very wide range of physiological effects.

Receptors outside the central nervous system

Glutamate receptors are believed to play a key role in receiving stimuli that elicit the "umami" taste, one of the five basic flavors according to the latest research in this area. Because of this, receptors of this class are known to exist on the tongue, specifically on the taste buds.

Ionotropic glutamate receptors are also known to exist in cardiac tissue, although their role in this area is still unknown. The discipline known as "immunhistochemistry" has located some of these receptors in terminal nerves, ganglia, conductive fibers, and some cardiomyocytes.

On the other hand, it is also possible to find a small number of these receptors in certain regions of the pancreas. Its main function here is to regulate the secretion of substances like insulin and glucagon. This has opened the door to research on the possibility of regulating diabetes using glutamate antagonists.

We also know today that the skin has a certain amount of NMDA receptors, which can be stimulated to produce an analgesic effect. In short, glutamate has very varied effects throughout the body, and its receptors are located throughout the body.

Features

We have already seen that glutamate is the most abundant neurotransmitter in the mammalian brain. This is mainly due to the fact that it fulfills a large number of functions in our body. Here we tell you which are the main ones.

Supports normal brain function

Glutamate is the most important neurotransmitter in regulating normal brain functions. Virtually all excitatory neurons in the brain and spinal cord are glutamatergic.

Glutamate sends signals both to the brain and throughout the body. These messages help with functions such as memory, learning, or reasoning, in addition to playing a secondary role in many other aspects of the functioning of our brain.

For example, today we know that with low glutamate levels it is impossible to form new memories. Furthermore, an abnormally low amount of this neurotransmitter can trigger attacks of schizophrenia, epilepsy, or psychiatric problems such as depression and anxiety.

Even studies with mice show that abnormally low levels of glutamate in the brain can be linked to autism spectrum disorders.

It is a precursor to GABA

Glutamate is also the base that the body uses to form another very important neurotransmitter, gamma-aminobutyric acid (GABA). This substance plays a very important role in learning, in addition to muscle contraction. It is also associated with functions such as sleep or relaxation.

Improves the functioning of the digestive system

Glutamate can be absorbed from food, being this neurotransmitter the main source of energy for the cells of the digestive system, as well as an important substrate for the synthesis of amino acids in this part of the body.

The glutamate in food causes several fundamental reactions throughout the body. For example, it activates the vagus nerve, in such a way that the production of serotonin in the digestive system is promoted. This encourages bowel movements, as well as increasing body temperature and energy production.

Some studies show that the use of oral glutamate supplements can improve digestion in patients with problems in this regard. In addition, this substance can also protect the stomach wall from the harmful effect of certain medications on it.

Regulates the cycle of appetite and satiety

Although we do not know exactly how this effect occurs, glutamate has a very important regulatory effect on the appetite circuit and satiety.

Thus, its presence in food makes us feel more hungry and want to eat more; but it also makes us feel more satisfied after taking it.

Improves the immune system

Some of the cells of the immune system also have glutamate receptors; for example, T cells, B cells, macrophages, and dendritic cells. This suggests that this neurotransmitter plays an important role in both the innate and adaptive immune systems.

Some studies using this substance as a medicine have shown that it can have a very beneficial effect on diseases such as cancer or bacterial infections. In addition, it appears to also protect to some extent against neurodegenerative disorders, such as Alzheimer's.

Improves muscle and bone function

Today we know that glutamate plays a fundamental role in the growth and development of bones, as well as in maintaining their health.

This substance prevents the appearance of cells that deteriorate bones, such as osteoclasts; and it could be used to treat diseases such as osteoporosis in humans.

On the other hand, we also know that glutamate plays a fundamental role in muscle function. During exercise, for example, this neurotransmitter is responsible for providing energy to muscle fibers and producing glutathione.

May increase longevity

Finally, some recent studies suggest that glutamate can have a very beneficial effect on the aging process of cells. Although it has not yet been tested in humans, animal experiments show that an increase in this substance in the diet can reduce mortality rates.

This effect is believed to be due to glutamate delaying the onset of symptoms of cellular aging, which is one of the leading causes of age-related death.

Dangers

When the natural levels of glutamate are altered in the brain or the body, it is possible to suffer all kinds of problems. This occurs whether there is less substance in the body than we need, or if the levels are raised in an exaggerated way.

Thus, for example, changes in glutamate levels in the body have been associated with mental disorders such as depression, anxiety, and schizophrenia. In addition, it also seems to be related to autism, Alzheimer's and all kinds of neurodegenerative diseases.

On the other hand, on a physical level it seems that an excess of this substance would be associated with problems such as obesity, cancer, diabetes, or amyotrophic lateral sclerosis. It could also have very detrimental effects on the health of certain components of the body, such as muscles and bones.

All these dangers would be related, on the one hand, to the excess of pure glutamate in the diet (in the form of monosodium glutamate, which seems to be capable of crossing the blood-brain barrier). In addition, they would also have to do with an excess of porosity in this same barrier.

conclusion

Glutamate is one of the most important substances produced by our body, and it plays a fundamental role in all kinds of functions and processes. AND

n this article you have learned how it works and what its main benefits are; but also the dangers it has when it is found in too high amounts in our body.

References

1. "What is glutamate? An examination of the functions, pathways and excitation of the glutamate neurotransmitter ”in: Neurohacker. Retrieved on: February 26, 2019 from Neurohacker: neurohacker.com.
2. "Overview of the Glutamatergic System" in: National Center for Biotechnology Information. Retrieved on: February 26, 2019 from the National Center for Biotechnology Information: ncbi.nlm.nih.gov.
3. "Glutamate receptor" in: Wikipedia. Retrieved on: February 26, 2019 from Wikipedia: en.wikipedia.org.
4. "8 Important Roles of Glutamate + Why It's Bad in Excess" in: Self Hacked. Retrieved on: February 26, 2019 from Self Hacked: selfhacked.com.
5. "Glutamate (neurotransmitter)" in: Wikipedia. Retrieved on: February 26, 2019 from Wikipedia: en.wikipedia.org.