THREONINE: CHARACTERISTICS, FUNCTIONS, DEGRADATION, BENEFITS - BIOLOGY - 2025

The threonine (Thr, T) or acid-Ls-threo α-amino-β-butyric, is one of the constituent amino acids of the cellular proteins. Since man and other vertebrate animals do not have biosynthetic routes for its production, threonine is considered one of the 9 essential amino acids that must be acquired through the diet.

Threonine was the last of the 20 common amino acids discovered in proteins, a fact that took place in history more than a century after the discovery of asparagine (1806), which was the first amino acid described.

Structure of the amino acid Threonine (Source: Clavecin via Wikimedia Commons)

It was discovered by William Cumming Rose in 1936, who coined the term “threonine” due to the structural similarity he found between this amino acid and threonic acid, a compound derived from treose sugar.

As a protein amino acid, threonine has multiple functions in cells, among which are the binding site for the typical carbohydrate chains of glycoproteins and the recognition site for protein kinases with specific functions (threonine / serine kinases proteins).

Similarly, threonine is an essential component of proteins such as tooth enamel, elastin and collagen and also has important functions in the nervous system. It is used as a dietary supplement and as a "reliever" of physiological states of anxiety and depression.

characteristics

Threonine belongs to the group of polar amino acids that have an R group or side chain devoid of positive or negative charges (uncharged polar amino acids).

The characteristics of its R group make it a highly water soluble amino acid (hydrophilic or hydrophilic), which is also true for the other members of this group, such as cysteine, serine, asparagine, and glutamine.

Together with tryptophan, phenylalanine, isoleucine and tyrosine, threonine is one of the five amino acids that has both glucogenic and ketogenic functions, since relevant intermediates such as pyruvate and succinyl-CoA are produced from its metabolism.

This amino acid has an approximate molecular weight of 119 g / mol; like many of the uncharged amino acids, it has an isoelectric point around 5.87 and its frequency in protein structures is close to 6%.

Some authors group threonine together with other amino acids with a "sweet" taste, among which are, for example, serine, glycine and alanine.

Structure

Α-amino acids such as threonine have a general structure, that is, it is common to all. This is distinguished by the presence of a carbon atom known as the "α carbon", which is chiral and to which four different types of molecules or substituents are attached.

This carbon shares one of its bonds with a hydrogen atom, another with the R group, which is characteristic for each amino acid, and the other two are occupied by the amino (NH2) and carboxyl (COOH) groups, which are common to all. amino acids.

The R group of threonine has a hydroxyl group that allows it to form hydrogen bonds with other molecules in aqueous media. Its identity can be defined as an alcoholic group (an ethanol, with two carbon atoms), which has lost one of its hydrogens to join the α carbon atom (-CHOH-CH3).

This -OH group can serve as a "bridge" or binding site for a wide variety of molecules (oligosaccharide chains, for example, can be attached to it during the formation of glycoproteins) and is therefore one of those responsible for the formation of modified derivatives of threonine.

The biologically active form of this amino acid is L-threonine and it is this that participates both in the conformation of protein structures and in the various metabolic processes where it acts.

Features

As a protein amino acid, threonine is part of the structure of many proteins in nature, where its importance and richness depend on the identity and function of the protein to which it belongs.

In addition to its structural functions in the conformation of the peptide sequence of proteins, threonine performs other functions both in the nervous system and in the liver, where it participates in the metabolism of fats and prevents their accumulation in this organ.

Threonine is part of the sequences recognized by serine / threonine kinases, which are responsible for numerous protein phosphorylation processes, essential for the regulation of multiplicity of functions and intracellular signaling events.

It is also used for the treatment of some intestinal and digestive disorders and it has been shown to be useful in reducing pathological conditions such as anxiety and depression.

L-threonine, likewise, is one of the amino acids required to maintain the pluripotent state of mouse embryonic stem cells, a fact that is apparently related to the metabolism of S-adenosyl-methionine and histone methylation events, which are directly involved in the expression of genes.

In the industry

A common property for many amino acids is their ability to react with other chemical groups such as aldehydes or ketones to form the characteristic "flavors" of many compounds.

Among these amino acids is threonine, which, like serine, reacts with sucrose during the roasting of certain foods and gives rise to “pyrazines”, typical aromatic compounds of roasted products such as coffee.

Threonine is present in many drugs of natural origin and also in many nutritional supplement formulations that are prescribed to patients with malnutrition or who have diets poor in this amino acid.

Another of the most notorious functions of L-threonine, which has been growing over time, is that of an additive in the preparation of concentrated feed for pigs and poultry production industries.

L-threonine is used in these industries as a food supplement in poor formulations from the protein point of view, since it provides economic advantages and alleviates the deficiencies in crude protein consumed by these farm animals.

The main form of production of this amino acid is, normally, by microbial fermentation and the world production figures for agricultural purposes for 2009 exceeded 75 tons.

Biosynthesis

Threonine is one of the nine essential amino acids for man, which means that it cannot be synthesized by the cells of the body and, therefore, that it must be acquired from proteins of animal or vegetable origin that are supplied with it. daily diet.

Plants, fungi, and bacteria synthesize threonine through similar pathways that may differ somewhat from one another. However, most of these organisms start from aspartate as a precursor, not only for threonine, but also for methionine and lysine.

Biosynthetic pathway in microbes

The L-threonine biosynthesis pathway in microorganisms such as bacteria consists of five different enzyme-catalyzed steps. The starting substrate, as discussed, is aspartate, which is phosphorylated by an ATP-dependent aspartate kinase enzyme.

This reaction produces the metabolite L-aspartyl phosphate (L-aspartyl-P) that serves as a substrate for the enzyme aspartyl semialdehyde dehydrogenase, which catalyzes its conversion to aspartyl semialdehyde in a NADPH-dependent manner.

Aspartyl semialdehyde can be used both for the biosynthesis of L-lysine and for the biosynthesis of L-threonine; in this case, the molecule is used by a NADPH-dependent homoserine dehydrogenase enzyme for the production of L-homoserine.

L-homoserine is phosphorylated to L-homoserine phosphate (L-homoserine-P) by an ATP-dependent homoserine kinase and said reaction product, in turn, is a substrate for the enzyme threonine synthase, capable of synthesizing L-threonine.

L-methionine can be synthesized from the L-homoserine produced in the previous step, therefore it represents a “competitive” pathway for the synthesis of L-threonine.

The L-threonine synthesized in this way can be used for protein synthesis or it can also be used downstream for the synthesis of glycine and L-leucine, two amino acids also relevant from the protein point of view.

Regulation

It is important to highlight that three of the five enzymes that participate in the biosynthesis of L-threonine in bacteria are regulated by the product of the reaction through negative feedback. These are aspartate kinase, homoserine dehydrogenase, and homoserine kinase.

Furthermore, the regulation of this biosynthetic pathway also depends on the cellular requirements of the other biosynthetic products related to it, since the formation of L-lysine, L-methionine, L-isoleucine and glycine is dependent on the production pathway of L-threonine.

Degradation

Threonine can be degraded by two different routes to produce pyruvate or succinyl-CoA. The latter is the most important product of threonine catabolism in humans.

Threonine metabolism occurs mainly in the liver, but the pancreas, although to a lesser extent, also participates in this process. This pathway begins with the transport of the amino acid across the plasma membrane of hepatocytes by means of specific transporters.

Production of pyruvate from threonine

The conversion of threonine to pyruvate occurs thanks to its transformation into glycine, which takes place in two catalytic steps that begin with the formation of 2-amino-3-ketobutyrate from threonine and by the action of the enzyme threonine dehydrogenase.

In humans, this route represents only between 10 and 30% of threonine catabolism, however, its importance is relative to the organism that is considered since, in other mammals, for example, it is much more catabolically relevant speaking.

Production of succinyl-CoA from threonine

As with methionine, valine and isoleucine, the carbon atoms of threonine are also used for the production of succunyl-CoA. This process begins with the conversion of the amino acid into α-ketobutyrate, which is subsequently used as a substrate for the α-keto acid dehydrogenase enzyme to yield propionyl-CoA.

The transformation of threonine into α-ketobutyrate is catalyzed by the enzyme threonine dehydratase, which involves the loss of one molecule of water (H2O) and another of an ammonium ion (NH4 +).

Propionyl-CoA is carboxylated into methylmalonyl-CoA through a two-step reaction that requires the entry of a carbon atom in the form of bicarbonate (HCO3-). This product serves as a substrate for a methylmalonyl-CoA mutase-coenzyme B12 dependent, which "epimerizes" the molecule to produce succinyl-CoA.

Other catabolic products

Additionally, the carbon skeleton of threonine can be used catabolically for the production of acetyl-CoA, which also has important implications from the energy point of view in the cells of the body.

In certain organisms, threonine also functions as a substrate for some biosynthetic pathways such as isoleucine, for example. In this case, through 5 catalytic steps, the α-ketobutyrate derived from threonine catabolism can be directed towards the formation of isoleucine.

Foods rich in threonine

Although most protein-rich foods contain a certain percentage of all amino acids, eggs, milk, soybeans, and gelatin have been found to be especially rich in the amino acid threonine.

Threonine is also in the meats of animals such as chicken, pork, rabbit, lamb, and various types of poultry. In foods of plant origin, it is abundant in cabbages, onions, garlic, chard and aubergines.

It is also found in rice, corn, wheat bran, legume grains, and in many fruits such as strawberries, bananas, grapes, pineapple, plums, and other protein-rich nuts such as walnuts or pistachios, among others.

Benefits of its intake

According to the expert committee of the World Food and Agriculture Health Organization (WHO, FAO), the daily requirement of threonine for an average adult human being is around 7 mg per kilogram of body weight, which should be acquired from food ingested with the diet.

These figures are derived from experimental data obtained from studies conducted with men and women, where this amount of threonine is sufficient to achieve a positive nitrogen balance in body cells.

However, studies carried out with children between 6 months and one year of age have shown that for these the minimum requirements of L-threonine are between 50 and 60 mg per kilogram of weight per day.

Among the main benefits of the intake of nutritional supplements or drugs with special formulations rich in L-threonine are the treatment of amyotrophic lateral sclerosis or Lou Gehrig's disease.

The additional supply of threonine favors the absorption of nutrients in the intestine and also contributes to the improvement of liver functions. It is also important for the transport of phosphate groups through cells.

Deficiency disorders

In young children there are inborn defects in threonine metabolism that cause growth retardation and other related metabolic disorders.

Deficiencies in this amino acid have been associated with some failures in infant weight gain, as well as other pathologies related to the lack of nitrogen retention and its loss in the urine.

Humans on diets low in threonine may be more prone to fatty liver and some intestinal infections related to this amino acid.

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