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Wednesday 15 October 2003

Definition: Methionine (abbreviated as Met or M) is an essential α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2SCH3. This essential amino acid is classified as nonpolar. Together with cysteine, methionine is one of two sulfur-containing proteinogenic amino acids.


As an essential amino acid, methionine is not synthesized 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:

- aspartokinase
- β-aspartate semialdehyde dehydrogenase
- homoserine dehydrogenase
- homoserine acyltransferase
- cystathionine-γ-synthase
- cystathionine-β-lyase
- methionine synthase (in mammals, this step is performed by - homocysteine methyltransferase)


Methionine is an intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and other phospholipids.

AUG codon and the "Start" message

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 significant, in that it carries 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.

Methionine regeneration in the folate-homocysteine cycle

Its derivative S-adenosyl methionine (SAM) serves as a methyl donor.

Methionine is converted to S-adenosylmethionine (SAM) by methionine adenosyltransferase. SAM serves as a methyl-donor in many methyltransferase reactions and is converted to S-adenosylhomocysteine (SAH). Adenosylhomocysteinase converts SAH to homocysteine.

There are two fates of homocysteine:

- 1. Methionine can be regenerated from homocysteine via methionine synthase. It can also be remethylated using glycine betaine (NNN-trimethyl glycine) to methionine via the enzyme Betaine-homocysteine methyltransferase (E.C., BHMT). Betaine-homocysteine methyltransferase 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.

- 2. Homocysteine can be converted to cysteine. 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 cystathionine-γ-lyase. 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).


Improper conversion of methionine can lead to atherosclerosis.

See also

- methionie biosynthesis

  • methionine synthase
  • methionine synthase reductase