Methionine

Methionine (abbreviated as Met or M) is a hydrophobic amino acid, whose chemical formula is: HO₂CCH(NH₂) CH₂CH₂SCH₃. Being hydrophobic, this essential amino acid is classified as nonpolar.

History

The American bacteriologist and immunologist John Howard Mueller verified in 1922 that the addition of a mixture of amino acids to colonies of streptococci (Streptococcus hemolyticus) was not sufficient for their growth. However, was achieved with the addition of casein. Thus Mueller assumed that casein must still contain at least one additional amino acid. During the later investigation of casein Mueller was for the first time able to isolate methionine. The elucidation of the structural formula and of the synthesis was achieved in 1926 by the British George Barger and his assistant Frederick Philip Coine, and Barger published in 1931 an improved synthesis. The name methionine, an abbreviation for "γ-methylthiol-α-amino-butyric acid", derives from work by S. Odake (1925).

Function

Along with cysteine, methionine is one of the two sulfur-containing proteinogenic amino acids. It is derived from S-Adenosyl methionine (SAM), serving as a methyl donor (SAM is also used by plants in the synthesis of ethylene, in a process known as the methionine cycle or Yang cycle).

Methionine is an intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and other phospholipids. Failures in the conversion of methionine can lead to atherosclerosis.

Encoding

Methionine is one of the two amino acids encoded by a single codon in the genetic code, the AUG (the other is tryptophan, which is encoded by the UGG codon), which is also the message that tells the ribosome to start processing. translation of a protein from mRNA. As a consequence, methionine is the first amino acid incorporated, despite the fact that it is usually eliminated in post-translational modifications in different cells.

Biosynthesis

Enzymes:

• EC 2.1.1.- Methyl Transfers SAM dependent
• EC 2.1.1.5 Betaina-homocysteine S-methyltransferasea
• EC 2.1.1.13 Syntase methine
• EC 2.3.1.30 Seine acetyltransferase
  

  Methionine metabolic summary
• EC 2.3.1.46 Homoserina O-succiniltransferasa
• EC 2.5.1.6 Methionine adenosiltransferase
• EC 2.5.1.47 Syntase cysteine
• EC 2.5.1.48 Cistationin γ-sintasa
• EC 3.3.1.1 S-Adenosilhocysteine hydrolasa
• EC 4.1.1.57 Metionine descarboxilasa
• EC 4.2.1.22 Cistationin-β-sintasa
• EC 4.4.1.1 Cistationin γ -liasa
• EC 4.4.1.8 Cistationin-β-liasa

As an essential amino acid, methionine is not synthesized in humans, therefore we have to ingest methionine or proteins that contain it. In plants and microorganisms, methionine is synthesized by a pathway that uses both aspartic acid and cysteine. First, aspartic acid is converted, via β-aspartyl-semialdehyde, to homoserine, introducing a pair of contiguous methylene groups. Homoserine becomes 0-succinylhomoserine, which after this reacts with cysteine to produce cystathionine, which is the key to giving way to homocysteine. Subsequently, the methylation of the thiol group starts from phosphates, which forms methionine. Both cystathionine-γ-synthetase and cystathionine-β-synthetase require Pyridoxyl-5'-phosphate as a cofactor, while homocysteine methyltransferase requires Vitamin B12 as a cofactor.

The enzymes involved in the biosynthesis of methionine are:

• Aspartokinasa
• β-aspartate semialdehyde dehydrogenase
• homoserin dehydrogenase
• acetyltransferase
• cistationin-γ-sintetase
• cistationin-β-liasa
• methionine syntheses (in mammals, this step is made by homocysteine methyltransferase)

Other biomedical pathways

Although mammals cannot synthesize methionine, it can still be used in a variety of biomedical pathways, such as in the generation of homocysteine:

Methionine is converted to S-adenosylmethionine (SAM) by methionine adenosyltransferase, which functions as a donor in many methyl transfer reactions and is converted to S-adenosylhomocysteine (SAH); adenocylhomocysteinase converts SAH to homocysteine.

There are two fates for homocysteine: methionine regeneration and cysteine formation.

Methionine regeneration

Methionine can be regenerated through the homocysteine pathway, involving methionine synthetase. In this regeneration from homocysteine, vitamin B12 is required. Therefore, an increase in homocysteine in clinical tests could be a sign of deficiency of this vitamin.

It can also be remethylated using betaine glycine (NNN-trimethylglycine) via the methionine pathway in which the enzyme beatin-homocysteine methyltransferase (E.C.2.1.1.5, BHMT). BHMT represents 1.5% of all soluble proteins in the liver and recent evidence suggests that it may have an even greater influence on methionine and homocysteine homeostasis than methionine synthetase.

Conversion to cysteine

Homocysteine can be converted to cysteine.

1. Cystationin-beta-sintetase (a PLP-dependent enzyme) combines homocysteine and seine to produce cystationin. Instead of degrading cystationin via cystationin-beta-liasa, this characteristic is the degradation of biosynthesis, in this case cystationin is rotated to cysteine and in α-ketobutirato producing cystationin-Y-liasa.
2. The dehydrogenated alpha-ketoacid converts alfa-ketobutirato into the same-CoA-sylum that is metabolized to ownnil-CoA in a three-step process.

Biosynthesis of polyamines

The polyamines spermine and spermidine require the transfer of a 3-aminopropyl substituent to the nitrogen of a putrescine or spermine molecule. Said group is obtained by decarboxylation of S-Adenosyl methionine (SAM). When spermine or spermidine is synthesized, S-methylthioriboside undergoes a series of transformations in such a way that methionine is recovered. This pathway is known as the Methionine Salvage Pathway ("Methionine Salvage Pathway").

Methionine rescue route

Enzymes:

• EC 1.13.11.54 Acirreductone dioxygenase dependent on iron (II).
• EC 1.13.11.53 Nickel-dependent dioxygenase (II)
• EC 2.5.1.22 Syntase sperm
• EC 2.6.1.5 Transamine (You can also transamine methionine)
• EC 2.7.1.100 S-Methyl-5-tiorribosa quinasa
• EC 3.1.3.77 Acirreductona sintasa
• EC 3.2.2.16 Methyltioadenosine nucleosidase
• EC 4.1.1.50 S-Adenosilmetionine descarboxilasa
• EC 4.2.1.109 Methylthoranbulous 1-phosphate dehydratesa
• EC 5.3.1.23 S-metil-5-tiorribosa-1-phosphate isomerasa

Other biosynthesis

Methionine is involved in ethylene biosynthesis, nicotianamine, salinosporamides, and various glucosinolates such as sinigrin, glucokerioline, glucoerucin, glucoiberin, glucoiberverine, glucorraphanin, and sulforraphane.

Dietary sources

In sesame seeds we can find quite high levels of methionine, as well as in Brazilian nuts, fish, meat and other plant seeds. There are numerous fruits and vegetables, as well as most legumes, that hardly contain methionine, only in small amounts.

Racemic methionine is often added as an ingredient to pet food.

Restriction in the consumption of methionine

Every day there are more studies that show that the restriction in the consumption of methionine can increase the lifespan of some animals.

In 2005, a study showed that restricting methionine intake without energy restriction in rodents increases their life span.