Methionine

Methionine ( or ; abbreviated as Met or M) is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein begins.

Function
Together with cysteine, methionine is one of two sulfur-containing proteinogenic amino acids. Its derivative S-adenosyl methionine (SAM) serves as a methyl donor. Methionine is an intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and other phospholipids. Improper conversion of methionine can lead to atherosclerosis.

This amino acid is also used by plants for synthesis of ethylene. The process is known as the Yang Cycle or the methionine cycle.

Methionine is one of only two amino acids encoded by a single codon (AUG) in the standard genetic code (tryptophan, encoded by UGG, is the other). The codon AUG is also the "Start" message for a ribosome that signals the initiation of protein translation from mRNA. As a consequence, methionine is incorporated into the N-terminal position of all proteins in eukaryotes and archaea during translation, although it is usually removed by post-translational modification. In bacteria, the derivative N-formylmethionine is used as the initial amino acid.

Rats fed a diet without methionine developed steatohepatitis. Administration of methionine ameliorated the pathological consequences of methionine deprivation.

Biosynthesis
As an essential amino acid, methionine is not synthesized de novo in humans, hence we must ingest methionine or methionine-containing proteins. In plants and microorganisms, methionine is synthesized via a pathway that uses both aspartic acid and cysteine. First, aspartic acid is converted via β-aspartyl-semialdehyde into homoserine, introducing the pair of contiguous methylene groups. Homoserine converts to O-succinyl homoserine, which then reacts with cysteine to produce cystathionine, which is cleaved to yield homocysteine. Subsequent methylation of the thiol group by folates affords methionine. Both cystathionine-γ-synthase and cystathionine-β-lyase require pyridoxyl-5'-phosphate as a cofactor, whereas homocysteine methyltransferase requires vitamin B12 as a cofactor.

Enzymes involved in methionine biosynthesis:
 * 1) aspartokinase
 * 2) β-aspartate semialdehyde dehydrogenase
 * 3) homoserine dehydrogenase
 * 4) homoserine O-transsuccinylase
 * 5) cystathionine-γ-synthase
 * 6) cystathionine-β-lyase
 * 7) methionine synthase (in mammals, this step is performed by homocysteine methyltransferase)



Other biochemical pathways
Although mammals cannot synthesize methionine, they can still use it in a variety of biochemical pathways:

Generation of homocysteine
Methionine is converted to S-adenosylmethionine (SAM) by (1) methionine adenosyltransferase.

SAM serves as a methyl-donor in many (2) methyltransferase reactions, and is converted to S-adenosylhomocysteine (SAH).

(3) Adenosylhomocysteinase converts SAH to homocysteine.

There are two fates of homocysteine: it can be used to regenerate methionine, or to form cysteine.

Regeneration of methionine
Methionine can be regenerated from homocysteine via (4) methionine synthase.

Homocysteine can also be remethylated using glycine betaine (NNN-trimethyl glycine, TMG) to methionine via the enzyme betaine-homocysteine methyltransferase (E.C.2.1.1.5, BHMT). BHMT makes up to 1.5% of all the soluble protein of the liver, and recent evidence suggests that it may have a greater influence on methionine and homocysteine homeostasis than methionine synthase.

Conversion to cysteine
Homocysteine can be converted to cysteine.


 * (5) Cystathionine-β-synthase (a PLP-dependent enzyme) combines homocysteine and serine to produce cystathionine. Instead of degrading cystathionine via cystathionine-β-lyase, as in the biosynthetic pathway, cystathionine is broken down to cysteine and α-ketobutyrate via (6) cystathionine-γ-lyase.
 * (7) The enzyme α-ketoacid dehydrogenase converts α-ketobutyrate to propionyl-CoA, which is metabolized to succinyl-CoA in a three-step process (see propionyl-CoA for pathway).

Synthesis
Racemic methionine can be synthesized from diethyl sodium phthalimidomalonate by alkylation with chloroethylmethylsulfide (ClCH2CH2SCH3) followed by hydrolysis and decarboxylation.

Dietary sources
High levels of methionine can be found in sesame seeds, Brazil nuts, fish, meats and some other plant seeds; methionine is also found in cereal grains. Most fruits and vegetables contain very little of it. Most legumes are also low in methionine. The complement of cereal (methionine) and legumes (lysine), providing a complete protein, is a classic combination, found throughout the world, such as in rice and beans or tortilla and beans.

Racemic methionine is sometimes added as an ingredient to pet foods.

Methionine restriction
There is a growing body of evidence that shows restricting methionine consumption can increase lifespans in some animals.

A 2005 study showed methionine restriction without energy restriction extends mouse lifespan.

A study published in Nature showed adding just the essential amino acid methionine to fruit flies on a calorie restricted diet restored egg-laying without reducing lifespan.

Other uses
DL-methionine is sometimes given as a supplement to dogs; it helps keep dogs from damaging grass by reducing the pH of the urine.

Methionine is allowed as a supplement to organic poultry feed under the US certified organic program.