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

The tyrosine (Tyr, Y) is one of the 22 amino acids that make up proteins of all cells in living beings. Unlike other amino acids such as valine, threonine, tryptophan, leucine, lysine, and others, tyrosine is a "conditionally" essential amino acid.

The name "tyrosine" derives from the Greek word "tiros", which means cheese, as this amino acid was discovered for the first time in this food. The term was coined in 1846 by Liebig, who mixed cheese with potassium hydroxide and obtained an unknown compound, hardly soluble in water.

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

After the initial description, other researchers such as Warren de la Rue and Hinterberger obtained it from coccoid insects and horn proteins, respectively. Its separation from the hydrolysis of other proteins with hydrochloric acid was described in 1901 by Mörner.

Generally, this amino acid is obtained in mammals thanks to the hydroxylation of phenylalanine, although it is also absorbed in the intestine from proteins consumed with food.

Tyrosine has multiple functions in the human body and among these the most relevant are, perhaps, that of a substrate for the production of neurotransmitters and hormones such as adrenaline and thyroid hormone.

characteristics

Tyrosine weighs approximately 180 g / mol and its R group or side chain has a dissociation constant pKa of 10.07. Its relative abundance in cellular proteins does not exceed 4%, but it has multiple functions essential for human physiology.

This amino acid belongs to the group of aromatic amino acids, in which phenylalanine and tryptophan are also found. The members of this group have aromatic rings in their R groups or side chains and are generally hydrophobic or apolar amino acids.

Like tryptophan, tyrosine absorbs ultraviolet light and is one of the amino acid residues responsible for the absorbance of light at 280 nm of many proteins, making it useful for its characterization.

It is considered a "conditionally" essential amino acid since its biosynthesis in humans depends on phenylalanine, an essential amino acid. If the body meets its daily phenylalanine requirements, tyrosine can be synthesized without problem and is not a limiting amino acid.

However, if the diet is lacking in phenylalanine, the body will not only have an imbalance of this amino acid, but also of tyrosine. It is also important to note that the tyrosine synthesis reaction from phenylalanine is not reversible, so tyrosine cannot meet the cellular needs for phenylalanine.

Tyrosine also belongs to the group of amino acids with dual roles in the production of glycogenic and ketogenic metabolic intermediates, which are involved in the synthesis of glucose for the brain and in the formation of ketone bodies in the liver.

Structure

Like the rest of the amino acids, tyrosine, or β-parahydroxyphenyl-α-amino propionic acid, is an α-amino acid that has a central carbon atom, called α carbon and that is chiral, since it is linked to four different substituent atoms or molecules.

This chiral carbon is attached to two characteristic groups of amino acids: an amino group (NH2) and a carboxyl group (COOH). It also shares one of its bonds with a hydrogen atom and the remaining bond is occupied by the R group or proper side chain of each amino acid.

In the case of tyrosine, this group consists of an aromatic ring associated with a hydroxyl group (OH), which gives it the ability to form hydrogen bonds with other molecules and which gives it essential functional characteristics for certain enzymes.

Features

Tyrosine is a fundamental component of many proteins with a great diversity of biological activities and functions.

In humans and other mammals, this amino acid is used in the nervous and renal tissues for the synthesis of dopamine, epinephrine and norepinephrine, three related catecholaminergic neurotransmitters of great importance for body function.

It is also essential for the synthesis of ultraviolet radiation (UV) protectors such as melanin; some painkillers like endorphins and antioxidant molecules like vitamin E.

In the same way, this amino acid serves for the synthesis of tyrosine, octopamine and thyroid hormones through the organization of iodine in the tyrosine residue of thyroglobulin.

Tyramine is a vasoactive molecule found in the human body, and octopamine is an amine related to norepinephrine.

All these functions of tyrosine are possible thanks to its obtaining from dietary proteins or by hydroxylation of phenylalanine with the liver as the main organ of systemic supply of said amino acid.

Functions in plants

Tyrosine and some of the intermediates generated during its biosynthesis feed the biosynthetic pathways of metabolites specialized in defense, in the attraction of pollinators, in electronic transport and in structural support.

Biosynthesis

In humans, tyrosine is obtained from the diet or synthesized in a single step by liver cells from phenylalanine, an essential amino acid, through the reaction catalyzed by the enzyme phenylalanine hydroxylase complex.

This complex has oxygenase activity and is only present in the liver of humans or other mammals. The tyrosine synthesis reaction then involves the transfer of an oxygen atom to the para position of the aromatic ring of phenylalanine.

This reaction occurs at the same time that a water molecule is formed by the reduction of another molecular oxygen atom and the reducing power is provided directly by a NADPH conjugated with a tetrahydropterin molecule, which is similar to folic acid.

Biosynthesis in plants

In plants, tyrosine is synthesized de novo downstream of the "shikimate" pathway, which feeds other biosynthetic pathways for other aromatic amino acids such as phenylalanine and tryptophan.

In these organisms, the synthesis starts from a compound known as “corismate”, which is the end product of the shikimate pathway and, furthermore, the common precursor for all aromatic amino acids, certain vitamins and plant hormones.

Chorismate is converted to prephenate by the catalytic action of the enzyme chorismate mutase and this is the first “committed” step in the synthesis of tyrosine and phenylalanine in plants.

Phenate is converted to tyrosine by oxidative decarboxylation and transamination, which can occur in any order.

In one of the biosynthetic pathways, these steps can be catalyzed by specific enzymes known as prephenate-specific tyrosine dehydrogenase (PDH) (which converts prephenate to 4-hydroxyphenylpyruvate (HPP)) and tyrosine aminotransferase (which produces tyrosine from HPP), respectively.

Another route of synthesis of tyrosine from prephenate involves the transamination of prephenate to a non-proteinogenic amino acid called L-hydrogenate, catalyzed by the enzyme prephenate aminotransferase.

The L-arogenate is subsequently subjected to oxidative decarboxylation to form thyroxine, a reaction directed by an arogenate-specific tyrosine dehydrogenase enzyme, also known as ADH.

Plants preferentially use the hydrogenate route, whereas most microbes synthesize tyrosine from the prephenate-derived HPP.

Regulation

As is true of most amino acid biosynthetic pathways, plants have a strict system of regulation of the synthesis of aromatic amino acids, including tyrosine.

In these organisms, regulation occurs at many levels, since the mechanisms that control the shikimate pathway also control tyrosine production, a pathway for which there are also regulation mechanisms of their own.

However, the requirements of tyrosine and, therefore, the rigidity in the regulation of its biosynthesis, are specific for each plant species.

Degradation

The degradation or catabolism of tyrosine results in the formation of fumarate and acetoacetate. The first step in this pathway is the conversion of the amino acid to 4-hydroxyphenylpyruvate by a cytosolic enzyme known as tyrosine aminotransferase.

This amino acid can also be transaminated in the mitochondria of hepatocytes by an enzyme aspartate aminotransferase, although this enzyme is not very important under normal physiological conditions.

Through the degradation of tyrosine, succinyl acetoacetate can be produced, which can be decarboxylated to succinyl acetate. Succinyl acetate is the most potent inhibitor of the enzyme responsible for the synthesis of the heme group, the enzyme 5-aminolevulinic acid dehydratase.

Synthesis of epinephrine and norepinephrine

As mentioned, tyrosine is one of the main substrates for the synthesis of two very important neurotransmitters for the human body: adrenaline and noradrenaline.

This is initially used by an enzyme known as tyrosine hydroxylase, capable of adding an additional hydroxyl group to the aromatic ring of the R group of tyrosine, thereby forming the compound known as dopa.

Dopa gives rise to dopamine once it is enzymatically processed by an enzyme dopa decarboxylase, which removes the carboxyl group from the starting amino acid and merits a pyridoxal phosphate (FDP) molecule.

Dopamine is subsequently converted to norepinephrine by the action of the enzyme dopamine β-oxidase, which catalyzes the addition of a hydroxyl group to -CH that was part of the R group of tyrosine and that functioned as a "bridge" between the aromatic ring and α carbon.

Epinephrine is derived from norepinephrine by the action of phenylethanolamine N-methyltransferase, which is responsible for the S-adenosyl-methionine-dependent transfer of a methyl group (-CH3) to the free amino group of norepinephrine.

Tyrosine rich foods

As discussed above, tyrosine is a "conditionally" essential amino acid, as it is synthesized in the human body by hydroxylation of phenylalanine, an essential amino acid.

Therefore, if the intake of phenylalanine meets the body's demands, tyrosine is not a limiting factor for the normal functioning of cells. Tyrosine, however, is also acquired from proteins that are consumed with daily food.

Some studies report that the minimum daily intake of both tyrosine and phenylalanine should be between 25 and 30 mg per kilogram of weight, so an average person should consume more or less 875 mg of tyrosine per day.

The foods with the highest tyrosine content are cheese and soy. These also include beef, lamb, pork, chicken, and fish.

Some seeds and nuts such as walnuts also provide significant amounts of this amino acid, as do eggs, dairy products, grains, and cereals.

Benefits of its intake

Tyrosine is commonly consumed in the form of dietary or nutritional supplements, specifically for the treatment of the pathology known as phenylketonuria, suffered by patients who are unable to adequately process phenylalanine and, therefore, do not produce tyrosine.

It is thought that an increase in the amount of tyrosine consumed per day can improve cognitive functions related to learning, memory and alertness under stressful conditions, since its catabolism is related to the synthesis of the neurotransmitters adrenaline and noradrenaline.

Some people take tyrosine-rich tablets to stay alert during the day if they have lost a significant amount of sleep.

As this amino acid participates in the formation of thyroid hormone, its consumption can have positive effects on systemic metabolic regulation.

Deficiency disorders

Albinism and alkaptonuria are two pathologies related to the metabolism of tyrosine. The first condition is related to the defective synthesis of melanin from tyrosine and the second has to do with defects in the degradation of tyrosine.

Albinism is characterized by the lack of pigmentation in the skin, that is, patients who suffer from it have white hair and pinkish skin, since melanin is the pigment in charge of providing color to these structures.

This pathology has to do with a deficiency in the melanocyte-specific tyrosinase enzyme, which is responsible for converting tyrosine into DOPA-quinone, an intermediate in the synthesis of melanin.

Symptoms of alkaptonuria are obvious as exaggerated (dark) urine pigmentation and late-developing arthritis.

Other metabolic pathologies

In addition, there are other disorders related to tyrosine metabolism, among which are:

- Hereditary tyrosinemia type I: characterized by progressive liver degeneration and kidney dysfunction

- Hereditary tyrosinemia type II or Richner-Hanhart syndrome: which is evident as keratitis and ampullary lesions on the palms of the hands and soles of the feet

- Tyrosinemia type III: which can be asymptomatic or present as mental retardation

- "Hawkinsinuria": characterized by metabolic acidosis in childhood and the inability to thrive in growth

There are also other innate defects in tyrosine metabolism that have to do with deficiencies in the enzymes responsible for its degradation, such as tyrosine hydroxylase, responsible for the first step in the synthesis of dopamine from tyrosine.

References

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