METHIONINE: CHARACTERISTICS, FUNCTIONS, FOODS, BENEFITS - BIOLOGY - 2025

The methionine (Met, M) is classified into the group of nonpolar amino acids or amino acid hydrophobic. This amino acid contains sulfur (S) in its side chain that can react with metal atoms or with electrophilic groups.

Methionine was discovered by John Howard Mueller in the second decade of the 20th century. Mueller isolated methionine from casein, a protein he used to grow hemolytic streptococcal cultures.

Chemical structure of the amino acid Methionine (Source: Hbf878 via Wikimedia Commons)

The name "methionine" is an abbreviation of the chemical name of this amino acid: γ-methylthiol-α-aminobutyric acid, and was introduced by S. Odake in 1925.

It is an essential amino acid for mammals and can enter the pathway for the synthesis of cysteine, a non-essential amino acid, as long as the body obtains methionine from the diet. Plants and bacteria synthesize it from homocysteine, a derivative of cysteine ​​and homoserine.

Its catabolism implies, on the one hand, the elimination of nitrogen from its structure and its excretion as urea and, on the other, the transformation of its carbon chain into succinyl CoA.

Along with valine and threonine, methionine is considered a glucogenic amino acid, since these amino acids can convert to succinate and enter the Krebs cycle. The glucogenic amino acids are capable of producing carbohydrates and, therefore, glucose.

There are many foods rich in methionine such as tuna, meats, egg whites, cheeses, and nuts.

Methionine is essential for the synthesis of many proteins, fulfills important functions in the metabolism of fats, mainly for skeletal muscle, and also participates as an antioxidant.

There are numerous disorders related to the metabolism of methionine and sulfur that are associated with pathologies with different degrees of implications for health. Some induce homocysteine ​​accumulation, which is accompanied by thrombosis, central nervous system (CNS) disorders, severe mental and skeletal system retardation.

Others, such as the lack of adenosyltransferase, which is the first enzyme that acts in the degradation of methionine, results in the accumulation of methionine, a relatively benign pathology that is controlled by restricting foods rich in methionine in the diet.

characteristics

Methionine is an essential amino acid that is not produced by the human body or by many. This is an excellent antioxidant and a source of sulfur for our body.

The daily requirement of methionine for infants is 45 mg / day, in children it is 800 mg / day and in adults it is between 350 and 1,100 mg / day.

Methionine is one of the main sources of sulfur in the body; sulfur is a fundamental component of some vitamins such as thiamine or vitamin B1, of some hormones such as glucagon, insulin and some pituitary hormones.

It is in keratin, which is a protein in the skin, nails and hair, and is also important for the synthesis of collagen and creatine. Therefore, methionine, being the source of sulfur, is related to all the functions of sulfur or the organic substances that contain it.

Structure

The chemical formula of methionine is HO2CCH (NH2) CH2CH2SCH3 and its molecular formula is C5H11NO2S. It is a hydrophobic essential amino acid, classified within the apolar amino acids.

It has an α carbon attached to an amino group (-NH2), a carboxyl group (-COOH), a hydrogen atom and a side chain (-R) that contains sulfur and is constituted as follows: -CH2 -CH2-S-CH3.

All amino acids, with the exception of glycine, can exist as enantiomers in L or D form, so L-methionine and D-methionine can exist. However, only L-methionine is found in the structure of cellular proteins.

This amino acid has dissociation constants pK 1 of 2.28 and pK2 of 9.21, and an isoelectric point of 5.8.

Features

Methionine is an essential amino acid for the synthesis of many proteins, among which are some hormones, the constitutive proteins of the skin, hair and nails, etc.

It is used as a natural relaxant to sleep and is very important for the good condition of nails, skin and hair. It prevents some liver and heart diseases; prevents the accumulation of fats in the arteries and is essential for the synthesis of cysteine ​​and taurine.

It favors the use of fats as energy and intervenes in the transport and use of them, especially in skeletal muscle, which is why it is very important for muscular exercise.

Reduces histamine levels. It is a natural antioxidant, as it helps reduce free radicals. It also has antidepressant and anxiolytic properties.

Another recent use of methionine as a “radiotracer” for the imaging study in positron emission tomography (PET) in the field of neuro-oncology.

It also has extensive use as a radiocontrast for gliomas, both in the planning process of surgical extractions, as well as for monitoring the response to treatment and the evaluation of recurrences.

Recently, the use of methionine has been efficiently tested to improve the growth of soybean plants.

Biosynthesis

Methionine biosynthesis was described and published in 1931 by the British George Barger and his assistant Frederick Philip Coine.

Bacteria and plants can synthesize methionine and cysteine, however, most animals obtain methionine from the diet and cysteine ​​from a biosynthetic pathway that starts from methionine as the initial substrate (they also acquire cysteine ​​with the food consumed in the diet).

Biosynthetic pathway

Plants and bacteria use cysteine ​​as a source of sulfur and homoserine as a source of the carbon skeleton for the synthesis of methionine. Homoserine is synthesized from aspartate through three enzymatic reactions:

(1) Aspartate is converted to β-aspartyl phosphate by means of an aspartate kinase enzyme, then (2) it is converted to aspartic β-semialdehyde, which (3) thanks to the action of homoserine dehydrogenase generates homoserine.

The first step in the synthesis of methionine is the reaction of homoserine with succinyl-CoA to form O-succinyl homoserine. In this reaction, the succinyl-CoA is cleaved, releasing the CoA portion and the succinate binding to homoserine.

In the biosynthetic pathway, the regulated or control step is this first enzymatic reaction, since methionine, which is the final product, ends up inhibiting the homoserine succinyl transferase enzyme.

The second step in the synthesis is the reaction of O-succinyl homoserine with cysteine, which is catalyzed by the enzyme cystathionine γ-synthetase, with the generation of cystathionine.

The third reaction in this pathway is catalyzed by β-cystathionine, which clears cystathiotin so that sulfur is attached to a four-carbon side chain derived from homoserine. The result of this reaction is the formation of homocysteine ​​and the release of 1 pyruvate and 1 NH4 + ion.

The last reaction is catalyzed by homocysteine ​​methyltransferase, which has homocysteine ​​as a substrate and together with the coenzyme methylcobalamin (derived from vitamin B12 (cyanocobalamin)) transfers a methyl group from 5-methyltetrahydrofolate to the sulfhydryl group of homocysteine ​​and gives origin to methionine.

In this reaction, a tetrahydrofolate remains free.

Degradation

Methionine, isoleucine, and valine are catabolized to succinyl-CoA. Three fifths of the carbons in methionine form succinyl-CoA, the carbons in carboxyl form CO2, and the methyl group of methionine is removed as such.

The first step in the degradation of methionine involves the condensation of L-methionine with ATP by means of L-methionine adenosyl transferase giving rise to S-adenosyl-L-methionine, also called “active methionine”.

The S-methyl group is transferred to various acceptors and thus S-adenosyl-L-homocysteine ​​is formed, which loses an adenosine through hydrolysis and becomes L-homocysteine. Homocysteine ​​then binds to serine to form cystathionine. This reaction is catalyzed by cystathionine β-synthetase.

Cystathionine hydrolyzes and gives rise to L-homoserine and cysteine. This is how homocysteine ​​originates homoserine and serine generates cysteine, so this reaction is common for the biosynthesis of cysteine ​​from serine.

Homoserine deaminase then converts homoserine to α-ketobutyrate, releasing an NH4. Α-ketobutyrate, in the presence of CoA-SH and NAD +, forms propionyl-CoA, which is then converted to methylmalonyl-CoA and this is converted to succinyl-CoA.

In this way, part of the carbon chain of methionine ends up forming a gluconeogenic substrate, succinyl-CoA, which can then be integrated into the synthesis of glucose; it is for this reason that methionine is considered a glucogenic amino acid.

An alternative route for the degradation of methionine is its use as an energy substrate.

The nitrogen of methionine, like that of all amino acids, is removed from the α-carbon by transamination, and this α-amino group is finally transferred to L-glutamate. By oxidative deamination, this nitrogen enters the urea cycle and is eliminated in the urine.

Methionine rich foods

Foods rich in methionine include:

- The egg white.

- Dairy derivatives such as ripened cheese, cream cheese and yogurt.

- Fish, especially the so-called blue fish such as tuna or swordfish.

- Crab, lobster and shrimp are important sources of methionine.

- Pork, beef and chicken meats.

- Walnuts and other dried fruits are rich in methionine and represent protein substitutes for vegetarians and vegans.

- Sesame seeds, pumpkin and pistachio.

It is also found in black and white beans, soybeans, corn, and leafy green vegetables like turnip greens, spinach, and Swiss chard. Broccoli, zucchini, and squash are rich in methionine.

Benefits of its intake

Being an essential amino acid, its intake is essential to fulfill all the functions in which it participates. By promoting the transport of fats for energy fuel use, methionine protects the liver and arteries against the accumulation of fat.

Its intake is beneficial for the protection of the body against conditions such as fatty liver and atherosclerosis.

Methionine has been shown to be efficient for the treatment of some severe cases of nitric oxide-induced myeloneuropathies and macrocytic anemias that do not respond to vitamin B12 treatment.

The use of S-adenosyl-L-methionine (SAM) is effective as a natural and alternative treatment for depression. This is due to the fact that SAM is a methyl group donor that is involved in the synthesis of various neurotransmitters with antidepressant properties in the brain.

Oxidative stress is involved, at least in part, in the damage of various organs, including the liver, kidneys, and brain. The use of antioxidants such as methionine has been postulated to prevent and correct the damage caused by oxidative stress.

Deficiency disorders

There are some pathologies related to the metabolism of methionine, which have to do with its intestinal absorption, which results in the accumulation of certain metabolites or the frank deficit of the amino acid.

In the case of methionine metabolic disorders, the most common are the so-called homocystinuria, which are types I, II, III and IV:

Type I homocystinuria is due to cystathionine β-synthetase deficiency and is associated with clinical symptoms similar to thrombosis, osteoporosis, lens dislocation, and frequently mental retardation.

Type II homocystinuria is caused by a deficiency of N5N10-methylenetetrahydrofolate reductase. Type III homocystinuria is due to a decrease in N5-methyltetrahydrofolate-homocysteine ​​transmethylase, due to a deficiency in methylcobalamin synthesis.

And finally, type IV homocystinuria is associated with a reduction in N5-methyltetrahydrofolate-homocysteine ​​transmethylase due to defective cobalamin absorption.

Homocystinuria are inherited defects in methionine metabolism and occur frequently in 1 in 160,000 newborns. In this pathology, about 300 mg of homocystine are excreted daily along with S-adenosyl methionine, which is accompanied by an increase in plasma methionine.

Reducing the intake of methionine and increasing cysteine ​​in the diet early in life prevents the pathological changes induced by these diseases and allows normal development.

In the case of methionine malabsorption deficiency, the most important effects are related to failures in the myelination of the nerve fibers of the central nervous system (CNS) that can be associated with a certain degree of mental retardation.

References

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