TRYPTOPHAN: CHARACTERISTICS, STRUCTURE, FUNCTIONS, BENEFITS - BIOLOGY - 2024

The tryptophan (Trp, W) is an amino acid classified within the group of essential amino acids because the human body can not synthesize and must obtain it through diet.

Some foods such as milk and its derivatives, meats, eggs and some cereals such as quinoa and soy contain essential amino acids and, therefore, are an important source of tryptophan.

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

More than 300 different amino acids are known in nature and of these only 22 constitute the monomeric units of cellular proteins. Among the latter, 9 are essential amino acids, including tryptophan, however, the essentiality of each differs from one species to another.

Tryptophan has various functions, including its participation in protein synthesis, in the synthesis of serotonin, which is a powerful vasoconstrictor and neurotransmitter, of melatonin and in the synthesis of the cofactor NAD.

In the plant kingdom, tryptophan is a fundamental precursor of the plant hormone auxin (indole-3-acetic acid). It can be synthesized by some bacteria such as E. coli from chorismate, which is produced from some glycolytic derivatives such as phosphoenolpyruvate and erythrose-4-phosphate.

Its degradation in mammals occurs in the liver, where it is used for the synthesis of acetyl coenzyme A (acetyl-CoA), and for this reason it is described as an amino acid called glucogenic, since it can enter the glucose formation cycle.

Several studies have been reported with controversial results related to the use of tryptophan as a dietary supplement for the treatment of some pathologies such as depression and some sleep disorders among others.

There are some diseases related to birth defects in amino acid metabolism. In the case of tryptophan, Hartnup's disease can be named, due to a deficiency of tryptophan-2,3-monooxygenase, a recessive hereditary disease characterized by mental retardation and pellagra-like skin disorders.

characteristics

Along with phenylalanine and tyrosine, tryptophan is in the group of aromatic and hydrophobic amino acids.

However, tryptophan is characterized by being a slightly hydrophobic amino acid since its aromatic side chain, due to its polar groups, attenuates this hydrophobicity.

Because they have conjugated rings, they have a strong absorption of light in the region of the spectrum near ultraviolet and this characteristic is frequently used for the structural analysis of proteins.

It absorbs ultraviolet light (between 250 and 290 nm) and, although this amino acid is not very abundant in the structure of most of the proteins in the human body, its presence represents an important contribution to the absorption capacity of light in the 280 nm region of most proteins.

Daily tryptophan requirements differ with age. In infants between 4 and 6 months the average requirement is about 17 mg per kilogram of weight per day; in children from 10 to 12 years it is 3.3 mg per kilogram of weight per day and in adults it is 3.5 mg per kilogram of weight per day.

Tryptophan is absorbed through the gut and is a ketogenic and glucogenic amino acid at the same time.

Since it is a precursor of serotonin, an important neurotransmitter, tryptophan must reach the central nervous system (CNS) and for this it must cross the blood-brain barrier, for which there is a specific active transport mechanism.

Structure

Tryptophan has a molecular formula C11H12N2O2 and this essential amino acid has an aromatic side chain.

Like all amino acids, tryptophan has an α carbon atom attached to an amino group (NH2), a hydrogen atom (H), a carboxyl group (COOH) and a side chain (R) formed by a heterocyclic structure, the indole group.

Its chemical name is 2-amino-3-indolyl propionic acid, it has a molecular mass of 204.23 g / mol. Its solubility at 20 ° C is 1.06 g in 100 g of water and it has a density of 1.34 g / cm3.

Features

In humans, tryptophan is used for protein synthesis and is essential for the formation of serotonin (5-hydroxytryptamine), a powerful vasoconstrictor, stimulant of smooth muscle contraction (especially in the small intestine) and a neurotransmitter capable of generate psychic stimulation, combat depression and regulate anxiety.

Tryptophan is a precursor in the synthesis of melatonin and therefore has implications for the sleep-wake cycles.

Said amino acid is used as a precursor in one of the three pathways for the formation of the cofactor NAD, a very important cofactor that participates in a great variety of enzymatic reactions related to oxidation-reduction events.

Tryptophan and some of its precursors are used for the formation of a plant hormone called auxin (indole-3-acetic acid). Auxins are plant hormones that regulate growth, development, and many other physiological functions of plants.

Biosynthesis

In organisms capable of synthesizing it, the carbon skeleton of tryptophan is derived from phosphoenolpyruvate and erythrose-4-phosphate. These, in turn, are formed from an intermediate of the Krebs cycle: oxaloacetate.

Phosphoenolpyruvate and erythrose-4-phosphate are used for the synthesis of chorismate in a seven-step enzymatic pathway. Phosphoenolpyruvate (PEP) is a product of glycolysis and erythrose-4-phosphate of the pentose phosphate pathway.

What is the synthesis route of chorismate like?

The first step in chorismate synthesis is the binding of PEP with erythrose-4-phosphate to form 2-keto-3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP).

This reaction is catalyzed by the enzyme 2-keto-3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHP synthase), which is inhibited by chorismate.

The second reaction involves the cyclization of DAHP by dehydroquinate synthase, an enzyme that requires the cofactor NAD, which is reduced during this reaction; as a result 5-dehydroquinate is produced.

The third step in this route involves the elimination of a water molecule from 5-dehydroquinate, a reaction catalyzed by the enzyme dehydroquinate dehydratase, the final product of which corresponds to 5-dehydro shikimate.

The keto group of this molecule is reduced to a hydroxyl group and, as a consequence, shikimate is formed. The enzyme that catalyzes this reaction is NADPH-dependent shikimate dehydrogenase.

The fifth step of the route involves the formation of shikimate 5-phosphate and the consumption of an ATP molecule by the action of an enzyme known as shikimate kinase, responsible for the phosphorylation of shikimate in position 5.

Subsequently, from shikimate 5-phosphate and by action of 3-enolpyruvyl shikimate-5-phosphate synthase, 3-enolpyruvyl shikimate 5-phosphate is generated. The mentioned enzyme promotes the displacement of the phosphoryl group of a second molecule of PEP by the hydroxyl group of the carbon in position 5 of the shikimate 5-phosphate.

The seventh and final reaction is catalyzed by chorismate synthase, which removes phosphate from 3-enolpyruvyl shikimate 5-phosphate and converts it to chorismate.

In the fungus N. crassa, a single multifunctional enzyme complex catalyzes five of the seven reactions in this pathway, and three other enzymes are added to this complex that end up generating tryptophan.

Synthesis of tryptophan in bacteria

In E. coli, the transformation of chorismate to tryptophan involves a pathway with five additional enzymatic steps:

First, the enzyme anthranilate synthase converts chorismate to anthranilate. A glutamine molecule participates in this reaction, which donates the amino group that binds to the indole ring of tryptophan and is converted into glutamate.

The second step is catalyzed by anthranilate phosphoribosyl transferase. In this reaction, a pyrophosphate molecule is displaced from 5-phosphoribosyl-1-pyrophosphate (PRPP), an energy-rich metabolite, and N- (5′-phosphoribosyl) -anthranilate is formed.

The third reaction in this route of tryptophan synthesis involves the participation of the enzyme phosphoribosyl-anthranilate isomerase. Here the furan ring of the N- (5′-phosphoribosyl) -anthranilate is opened and 1- (o-carboxyphenylamino) -1-deoxyribulose 5-phosphate is formed by tautomerization.

Later, indole-3-glycerol phosphate is formed, in a reaction catalyzed by indole-3-glycerol phosphate synthase, where a CO2 and a H2O molecule are released and 1- (o-carboxyphenylamino) -1- is cyclized. deoxyribulose 5-phosphate.

The last reaction of this pathway ends up forming tryptophan when tryptophan synthase catalyzes the reaction of indole-3-glycerol phosphate with a molecule of PLP (pyridoxal phosphate) and another of serine, releasing glyceraldehyde 3-phosphate and forming tryptophan.

Degradation

In mammals, tryptophan is broken down to acetyl-CoA in the liver in a pathway that involves twelve enzymatic steps: eight to reach α-ketoadipate and 4 more to convert α-ketoadipate to acetyl coenzyme A.

The order of degradation to α-ketoadipate is:

Tryptophan → N-formyl quinurenine → Quinurenine → 3-hydroxy quinurenine → 3-hydroxy-anthranilate → ε-semialdehyde 2-amino-3-carboxy muconic → ε-semialdehyde α-amino muconic → 2-amino muconate → α-ketoadipate.

The enzymes that catalyze these reactions respectively are:

Tryptophan 2-3-dioxygenase, kinurenine formamidase, NADPH-dependent monooxygenase, kinureninase, 3-hydroxy-anthranilate oxygenase, decarboxylase, NAD-dependent ε-semialdehyde α-aminonuconic dehydrogenase, and α-amino muconate reductase NADPH-dependent.

Once α-ketoadipate is generated, glutaryl-CoA is formed by oxidative decarboxylation. This, by ß-oxidation, forms Glutaconyl-CoA that loses a carbon atom in the form of bicarbonate (HCO3-), gains a water molecule and ends up as crotonyl-CoA.

Crotonyl-CoA, also by ß-oxidation, yields acetyl-CoA. Such acetyl-CoA can follow several pathways, notably gluconeogenesis, to form glucose, and the Krebs cycle, to form ATP, as needed.

However, this molecule can also be directed towards the formation of ketone bodies, which can finally be used as an energy source.

Foods rich in tryptophan

Red meat in general, chicken and fish (especially oily fish such as salmon and tuna) are especially rich in tryptophan. Milk and its derivatives, eggs, especially the yolk, are also foods with an abundant content of tryptophan.

Other foods that serve as a natural source of this amino acid are:

- Dried fruits such as walnuts, almonds, pistachios and cashews, among others.

- Rice cereals.

- Dry grains such as beans, lentils, chickpeas, soybeans, quinoa, etc.

- Brewer's yeast and fresh beans, bananas and plantains, pineapple or pineapple, avocado, plums, watercress, broccoli, spinach and chocolate.

Benefits of its intake

The consumption of tryptophan is absolutely necessary to synthesize all those proteins that include it in its structure and through its different functions it allows to regulate mood, sleep and wake cycles and a great variety of biochemical processes in which NAD participates..

In addition to the known effects on mood, serotonin (derived from tryptophan) is involved in multiple cognitive functions related to learning and memory, which are therefore also related to tryptophan.

There are data showing the relationship between mood, serotonin, and the gastrointestinal-brain axis as a system of bidirectional influences between the brain's emotional and cognitive centers and the peripheral function of the digestive tract.

Its use as a dietary supplement for the treatment of some disorders, especially those related to the central nervous system, has been highly controversial because its competitive transport with the much more abundant neutral amino acids makes it difficult to achieve significant and sustained increases in tryptophan after oral administration.

Despite these controversies, its use has been postulated as an adjuvant in:

- Pain treatment

- Sleep disorders

- Treatment of depression

- Treatment of manias

- reduced appetite

Deficiency disorders

Central tryptophan elimination or deficiency is associated with depression, attention failure, memory impairment, sleep disturbances, and anxiety.

In depressed and suicidal patients, alterations have been found in the concentration of tryptophan in the blood and in the cerebrospinal fluid. Also, some patients with anorexia nervosa show low serum levels of tryptophan.

Some polyuric patients, who lose vitamin B6 and zinc, frequently present phobias and anxiety and improve with dietary supplements rich in tryptophan.

Carcinoid syndrome is characterized by the presence of small intestinal tumors that cause diarrhea, vascular diseases and bronchoconstriction and is related to a deficiency of niacin and tryptophan

Pellagra is a pathological condition that is accompanied by diarrhea, dementia, dermatitis and can cause death, this is also treated with supplements of niacin and tryptophan.

Hartnup's disease has to do, among some things, with a defect in the metabolism of several amino acids, including tryptophan.

In the case of a deficiency of the enzyme tryptophan-2,3-monooxygenase, this is a recessive hereditary disease characterized by mental retardation and pellagra-like skin disorders.

References

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3. Jenkins, TA, Nguyen, JC, Polglaze, KE, & Bertrand, PP (2016). Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain axis. Nutrients, 8 (1), 56.
4. Kaye, WH, Barbarich, NC, Putnam, K., Gendall, KA, Fernstrom, J., Fernstrom, M.,… & Kishore, A. (2003). Anxiolytic effects of acute tryptophan depletion in anorexia nervosa. International Journal of Eating Disorders, 33 (3), 257-267.
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