GLUTAMIC ACID: CHARACTERISTICS, FUNCTIONS, BIOSYNTHESIS - BIOLOGY - 2024

The glutamic acid is one of the 22 amino acids that make up proteins in all living things and one of the most abundant in nature. Since the human body has intrinsic pathways for its biosynthesis, it is not considered essential.

Together with aspartic acid, glutamic acid belongs to the group of negatively charged polar amino acids and, according to the two existing nomenclature systems (of three or one letter), it is denoted as " Glu " or as " E ".

Structure of the amino acid Glutamic Acid (Source: Hbf878 via Wikimedia Commons)

This amino acid was discovered in 1866 by the German chemist Rittershausen while he was studying hydrolyzed wheat gluten, hence its name "glutamic". After its discovery, its presence has been determined in a large part of living beings, so it is thought that it has essential functions for life.

L-glutamic acid is considered one of the most important mediators in the transmission of excitatory signals in the central nervous system of vertebrate animals and is also necessary for normal brain function, as well as for cognitive development, memory and The learning.

Some of its derivatives also have important functions at an industrial level, especially with regard to culinary preparations, as it helps to enhance the flavor of food.

characteristics

Despite not being an essential amino acid for humans, glutamate (the ionized form of glutamic acid) has important nutritional implications for animal growth and has been suggested to have a much higher nutritional value than other non-essential amino acids.

This amino acid is especially abundant in the brain, especially in the intracellular space (cytosol), which allows the existence of a gradient between the cytosol and the extracellular space, which is delimited by the plasma membrane of nerve cells.

Because it has many functions in excitatory synapses and that it exerts its functions by acting on specific receptors, its concentration is kept at controlled levels, especially in the extracellular environment, since these receptors generally "look" out of the cells.

The sites of highest concentration of glutamate are the nerve terminals, however, its distribution is conditioned by the energy needs of the cells throughout the body.

Depending on the type of cell, when glutamic acid enters the cell it can be directed towards the mitochondria, for energy purposes, or it can be redistributed towards synaptic vesicles and both processes employ specific intracellular transport systems.

Structure

Glutamic acid, like the rest of the amino acids, is an α-amino acid that has a central carbon atom (which is chiral), the α carbon, to which four other groups are attached: a carboxyl group, an amino group, a hydrogen atom and a substituent group (side chain or R group).

The R group of glutamic acid gives the molecule a second carboxyl group (-COOH) and its structure is -CH2-CH2-COOH (-CH2-CH2-COO- in its ionized form), so the sum of atoms total carbon of the molecule is five.

This amino acid has a relative mass of 147 g / mol and the dissociation constant (pKa) of its R group is 4.25. It has an isoelectric point of 3.22 and the average protein presence index is around 7%.

Since at a neutral pH (around 7), glutamic acid is ionized and has a negative charge, it is classified within the group of negatively charged polar amino acids, a group in which aspartic acid (aspartate, in its ionized form is also included).

Features

Glutamic acid or its ionized form, glutamate, has multiple functions, not only from a physiological point of view, but also from an industrial, clinical and gastronomic point of view.

Physiological functions of glutamic acid

One of the most popular physiological functions of glutamic acid in the body of most vertebrates is its role as an excitatory neurotransmitter in the brain. It has been determined that more than 80% of excitatory synapses communicate using glutamate or one of its derivatives.

Among the functions of synapses that use this amino acid during signaling are recognition, learning, memory, and others.

Glutamate is also related to the development of the nervous system, to the initiation and elimination of synapses, and to cell migration, differentiation, and death. It is important for communication between peripheral organs such as the alimentary tract, pancreas, and bones.

Additionally, glutamate has functions both in the protein and peptide synthesis processes, as well as in the synthesis of fatty acids, in the regulation of cellular nitrogen levels and in the control of the anionic and osmotic balance.

It serves as a precursor for different intermediates of the tricarboxylic acid cycle (Krebs cycle) and also for other neurotransmitters such as GABA (gamma aminobutyric acid). In turn, it is a precursor in the synthesis of other amino acids such as L-proline, L-arginine and L-alanine.

Clinical applications

Different pharmaceutical approaches are mainly based on glutamic acid receptors as therapeutic targets for the treatment of psychiatric diseases and other memory-related pathologies.

Glutamate has also been used as an active agent in different pharmacological formulations designed to treat myocardial infarctions and functional dyspepsia (gastric problems or indigestion).

Industrial applications of glutamic acid

Glutamic acid and its derivatives have diverse applications in different industries. For example, the monosodium salt of glutamate is used in the food industry as a seasoning.

This amino acid is also the starting material for the synthesis of other chemicals and glutamic polyacid is a natural anionic polymer that is biodegradable, edible and non-toxic to humans or the environment.

In the food industry it is also used as a thickener and as a "reliever" agent of the bitterness of different foods.

It is also used as a cryoprotectant, as a "curable" biological adhesive, as a drug carrier, for the design of biodegradable fibers and hydrogels capable of absorbing large amounts of water, among others.

Biosynthesis

All amino acids are derived from glycolytic intermediates, the Krebs cycle, or the pentose phosphate pathway. Glutamate, specifically, is obtained from glutamine, α-ketoglutarate and 5-oxoproline, all derived from the Krebs cycle.

The biosynthetic pathway for this amino acid is quite simple and its steps are found in almost all living organisms.

Glutamate and Nitrogen Metabolism

In nitrogen metabolism, it is through glutamate and glutamine that ammonium is incorporated into the different biomolecules of the body and, through transamination reactions, glutamate provides the amino groups of most amino acids.

Thus, this route involves the assimilation of ammonium ions to glutamate molecules, which takes place in two reactions.

The first step in the pathway is catalyzed by an enzyme known as glutamine synthetase, which is present in virtually all organisms and is involved in the reduction of glutamate and ammonia to produce glutamine.

In bacteria and plants, instead, glutamate is produced from glutamine by the enzyme known as glutamate synthase.

In animals, this is produced from the transamination of α-ketoglutarate, which takes place during the catabolism of amino acids. Its main function in mammals is to convert toxic free ammonia into glutamine, which is transported by the blood.

In the reaction catalyzed by the enzyme glutamate synthase, α-ketoglutarate goes through a reductive amination process, where glutamine participates as a donor of the nitrogen group.

Although it occurs in a much smaller proportion, glutamate is also produced in animals by the one-step reaction between α-ketoglutarate and ammonium (NH4), which is catalyzed by the enzyme L-glutamate dehydrogenase, ubiquitous in virtually all living organisms.

Said enzyme associates with the mitochondrial matrix and the reaction it catalyzes can be written roughly as follows, where NADPH works in supplying reducing power:

α-ketoglutarate + NH4 + NADPH → L-glutamate + NADP (+) + water

Metabolism and degradation

Glutamic acid is used by the cells of the body to serve different purposes, among which are protein synthesis, energy metabolism, ammonium fixation, or neurotransmission.

Glutamate taken from the extracellular medium in some types of nerve cells can be "recycled" by converting it into glutamine, which is released into extracellular fluids and taken up by neurons to be transformed back into glutamate, which is known as the glutamine cycle. -glutamate.

Once ingested with food in the diet, the intestinal absorption of glutamic acid generally ends in its transformation into other amino acids such as alanine, a process mediated by the cells of the intestinal mucosa, which also use it as a source of energy.

The liver, on the other hand, is responsible for converting it into glucose and lactate, from which chemical energy is extracted mainly in the form of ATP.

The existence of various glutamate metabolizing enzymes has been reported in different organisms, such is the case of glutamate dehydrogenases, glutamate-ammonium lyases, and glutaminases, and many of these have been implicated in Alzheimer's disease.

Glutamic Acid Rich Foods

Glutamic acid is present in most of the foods consumed by man and some authors claim that for a human being weighing 70 kg, the daily intake of glutamic acid derived from the diet is around 28 g.

Among the foods richest in this amino acid are those of animal origin, where meat (bovine, pig, ovine, etc.), eggs, dairy and fish stand out. Plant-based foods rich in glutamate include seeds, grains, asparagus, and others.

In addition to the different types of foods naturally rich in this amino acid, a derivative thereof, the monosodium salt of glutamate is used as an additive to enhance or increase the flavor of many dishes and industrially processed foods.

Benefits of its intake

Glutamate added to different culinary preparations helps to "induce" taste and to improve the sensation of taste in the oral cavity, which apparently has important physiological and nutritional significance.

Clinical trials have shown that the ingestion of glutamic acid has potential applications in the treatment of "disorders" or oral pathologies related to taste and "hyposalivation" (low production of saliva).

Likewise, glutamic acid (glutamate) is a nutrient of great importance for the maintenance of normal activity of cells in the intestinal mucosa.

The supply of this amino acid to rats that have undergone chemotherapeutic treatments has been shown to increase the immunological characteristics of the intestine, in addition to maintaining and enhancing the activity and functions of the intestinal mucosa.

In Japan, on the other hand, medical diets based on foods rich in glutamic acid have been designed for patients undergoing "percutaneous endoscopic gastronomy", that is, they must be fed through a stomach tube that is connected through the wall abdominal.

This amino acid is also used to induce appetite in elderly patients with chronic gastritis who are normally inappetent.

Lastly, studies related to the oral supply of glutamic acid and arginine suggest that they are involved in the positive regulation of genes related to adipogenesis in muscle tissue and lipolysis in adipose tissues.

Deficiency disorders

Since glutamic acid serves as a precursor in the synthesis of various types of molecules such as amino acids and other neurotransmitters, genetic defects associated with the expression of enzymes related to its biosynthesis and recycling can have consequences for the health of any animal's body.

For example, the enzyme glutamic acid decarboxylase is responsible for the conversion of glutamate to gamma aminobutyric acid (GABA), a neurotransmitter essential for inhibitory nerve reactions.

Therefore, the balance between glutamic acid and GABA is of utmost importance for the maintenance of control of cortical excitability, since glutamate functions mainly at excitatory nerve synapses.

In turn, since glutamate is involved in a series of brain functions such as learning and memory, its deficiency could cause defects in these classes of cognitive processes that require it as a neurotransmitter.

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