ISOLEUCINE: CHARACTERISTICS, FUNCTIONS, BIOSYNTHESIS, FOOD - BIOLOGY - 2024

The isoleucine (Ile, I) is one of the 22 naturally occurring amino acids as part of proteins. Since the human body, like that of some other mammals, cannot synthesize it, isoleucine is among the 9 essential amino acids that must be obtained from the diet.

This amino acid was isolated for the first time in 1903 by the scientist F. Ehrlich from the nitrogenous constituents of beet or beetroot molasses. Later, the same author separated isoleucine from the decomposition products of fibrin and other proteins.

Chemical structure of the amino acid Isoleucine (Source: Clavecin via Wikimedia Commons)

It is a non-polar amino acid present in a large part of the cellular proteins of living organisms, in addition, it is part of the group of branched chain amino acids BCAAs (from the English B ranched C hain A mino A cids), along with leucine and valine.

It has functions in the establishment of the tertiary structure of many proteins and, in addition, it participates in the formation of various metabolic precursors related to cellular energy metabolism.

characteristics

Isoleucine is classified within the group of nonpolar amino acids with R groups or chains of an aliphatic nature, that is, with hydrophobic hydrocarbon chains.

Due to this characteristic, the amino acids of this group such as alanine, valine and leucine, tend to remain close to each other, which contributes to the stabilization of the proteins of which they are a part through hydrophobic interactions.

This non-polar amino acid weighs approximately 131 g / mol and is present in proteins in a proportion close to 6%, often "buried" in the center of them (thanks to its hydrophobic qualities).

Structure

Isoleucine is an α-amino acid that, like the other amino acids, has a central carbon atom called α carbon (which is chiral), to which four different groups are attached: a hydrogen atom, an amino group (-NH2), a carboxyl group (-COOH) and a side chain or R group.

The R group of isoleucine consists of a single branched hydrocarbon of 4 carbon atoms (-CH3-CH2-CH (CH3)) in whose chain there is also a chiral carbon atom.

Due to this characteristic, isoleucine has four possible forms: two of them are the optical isomers known as L-isoleucine and D-isoleucine and the other two are diastereoisomers of L-isoleucine. The predominant form in proteins is L-isoleucine.

The molecular formula of isoleucine is C6H13NO2 and its chemical name is α-amino-β-methyl-β-ethylpropionic acid or 2-amino-3-methyl pentatonic acid.

Features

Isoleucine has multiple physiological functions in animals including the

- Wound healing

- Nitrogen waste detoxification

- Stimulation of immune functions and

- Promotion of the secretion of different hormones.

It is considered a glucogenic amino acid, as it serves as a precursor molecule for the synthesis of intermediates of the citric acid cycle (Krebs cycle) that later contribute to the formation of glucose in the liver.

For this reason, isoleucine is believed to participate in the regulation of plasma glucose levels, which has important implications from the body's energy point of view.

Isoleucine contributes to the synthesis routes of glutamine and alanine, working in favor of the balance between branched chain amino acids.

In the clinical setting, some authors point out that an increase in the concentrations of isoleucine, leucine, tyrosine and valine can be characteristic markers of cells affected by tumors, followed by an increase in the levels of glutamine.

Other functions

Different scientific investigations have shown that isoleucine is necessary for the synthesis of hemoglobin, the protein that is responsible for transporting oxygen in the blood of many animals.

In addition, this amino acid activates the entry of nutrients into the cells; Some studies reveal that during prolonged fasting it is able to replace glucose as an energy source and, in addition, it is a ketogenic amino acid.

Ketogenic amino acids are those whose carbon skeletons can be stored as fatty acids or carbohydrates, thus they function in the energy reserve.

Isoleucine and the other branched-chain amino acids (in addition to growth factors and environmental conditions) work on the activation of the Rapamycin target signaling pathway, mTOR (m echanistic T arget of R apamycin).

This pathway is an important signaling pathway in eukaryotes capable of controlling cell growth and metabolism, as well as protein synthesis and autophagy events. In addition, it controls the progress of aging and some pathologies such as cancer or diabetes.

Biosynthesis

Humans and other animals are unable to synthesize isoleucine, but this is part of cellular proteins thanks to its acquisition from the food we consume daily.

Plants, fungi and most microorganisms are capable of synthesizing this amino acid from somewhat complex routes that, in general, are interconnected with those of other amino acids also considered essential for man.

There are, for example, pathways for the production of isoleucine, lysine, methionine, and threonine from aspartate.

In bacteria, specifically, isoleucine is produced from the amino acid threonine, via pyruvate, through a pathway that involves the condensation of 2 of the pyruvate carbons with an α-ketobutyrate molecule derived from threonine.

The reaction begins with the action of the enzyme threonine dehydratase, which catalyzes the dehydration of threonine to produce α-ketobutyrate and ammonium (NH3). Subsequently, the same enzymes that participate in the biosynthesis of valine contribute to the steps of

- Transamination

- Oxidative decarboxylation of the corresponding ketoacids and

- Dehydrogenation.

In this type of microorganisms, the synthesis of amino acids such as lysine, methionine, threonine and isoleucine is highly coordinated and regulated, especially by negative feedback, where the products of the reactions inhibit the activity of the enzymes involved.

Despite the fact that isoleucine, like leucine and valine, are essential amino acids for man, the aminotransferase enzymes present in body tissues can reversibly interconvert them to their corresponding α-keto acids, which can eventually replace them in the diet.

Degradation

Like many of the amino acids that are known in nature, isoleucine can be degraded to form intermediaries of different metabolic pathways, among which the Krebs cycle stands out (which provides the greatest amount of coenzymes that work for the production of energy or for the biosynthesis of other compounds).

Isoleucine, tryptophan, lysine, phenylalanine, tyrosine, threonine, and leucine can all be used to produce acetyl-CoA, a key metabolic intermediate for multiple cellular reactions.

Unlike other amino acids, branched chain amino acids (leucine, isoleucine, and valine) are not degraded in the liver, but are oxidized as fuels in muscle, brain, kidneys, and adipose tissue.

These organs and tissues can use these amino acids thanks to the presence of an aminotransferase enzyme capable of acting on all three and producing their corresponding α-keto amino acids.

Once these oxidized amino acid derivatives are produced, the α-keto acid dehydrogenase enzyme complex catalyzes their oxidative decarboxylation, where it releases a carbon dioxide (CO2) molecule and produces an acyl-CoA derivative of the amino acids in question.

Pathologies related to isoleucine metabolism

Defects in the metabolism of isoleucine and other amino acids can cause a variety of strange and complex pathologies, such as, for example, the disease "Maple Syrup Urine" (urine with the smell of maple syrup) or branched chain ketoaciduria.

As its name implies, this disease is characterized by the distinctive aroma of the urine of patients who suffer from it, as well as vomiting, seizures, mental retardation and premature death.

It has to do, specifically, with errors in the enzyme complex α-ketoacid dehydrogenase, with which branched chain amino acids such as isoleucine and its oxidized derivatives are excreted in the urine.

Altogether, pathologies related to the catabolism of branched chain amino acids such as isoleucine are known as organic acidurias, although those that are directly related to this amino acid are quite rare.

Foods rich in isoleucine

This amino acid is abundant in the muscular tissues of animals, which is why meats of animal origin such as beef, pork, fish and other similar ones such as lamb, chicken, turkey, venison, among others, are rich in it.

It is also found in dairy products and their derivatives such as cheese. It is in eggs and also in different types of seeds and nuts, as an essential part of the proteins that make them up.

It is abundant in soybeans and peas, as well as in yeast extracts used for various food purposes.

The plasma levels of isoleucine for an adult human being are between 30 and 108 μmol / l, for children and young people between 2 and 18 years of age it is between 22 and 107 μmol / l and for infants between 0 and 2 years old they are approximately between 26 and 86 μmol / l.

These data suggest that the consumption of foods rich in this and other related amino acids is necessary for the maintenance of many of the physiological functions of the organism, since human beings are unable to synthesize it de novo.

Benefits of its intake

Isoleucine nutritional supplements usually contain other essential branched chain amino acids such as valine or leucine or others.

Among the most common examples of isoleucine consumption are nutritional supplements used by athletes to increase the percentage of muscle mass or protein synthesis. However, the scientific bases on which these practices are supported are constantly debated, and their results are not completely guaranteed.

Isoleucine, however, is used to counteract the metabolic effects of vitamin deficiency (pellagra) characteristic of patients who have diets rich in sorghum and corn, which are foods high in leucine, which can affect the metabolism of tryptophan and of nicotinic acid in humans.

The effects of pellagra in experimental rats, for example, involve growth delays, which are overcome with isoleucine supplementation.

- In the animal production industry

In the area of ​​animal production, amino acids such as lysine, threonine, methionine and isoleucine have been used in pilot tests for feeding pigs growing under controlled conditions.

Isoleucine, in particular, appears to have effects on nitrogen assimilation, although it does not contribute to weight gain in these farm animals.

- In some clinical conditions

Some publications suggest that isoleucine is capable of lowering plasma glucose levels, so its intake is recommended in patients suffering from disorders such as diabetes or low rates of insulin production.

Viral infections

Isoleucine supplementation has proven useful in patients infected with rotavirus that cause diseases such as gastroenteritis and diarrhea in young children and other young animals.

Recent studies conclude that the consumption of this amino acid by experimental animals with the aforementioned characteristics (infected with rotavirus) helps in the growth and performance of the innate immune system thanks to the activation of the PRR signaling pathways or receptors with recognition of patterns.

Deficiency disorders

Isoleucine deficiency can lead to problems with vision, skin (such as dermatitis), and intestines (evident as diarrhea and other gastrointestinal manifestations).

Since it is an essential amino acid for the formation and synthesis of hemoglobin, as well as for the regeneration of erythrocytes (blood cells), severe isoleucine deficiencies can have serious physiological consequences, especially related to anemia and other hematological diseases..

This has been demonstrated experimentally in "normal" rodents which have been given diets poor in this isoleucine, which ends with the development of significant anemic conditions.

However, isoleucine participates in the formation of hemoglobin only in infants, since the protein of the adult human being does not possess significant amounts of such amino acid; this means that isoleucine deficiency is most evident during the early stages of development.

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