Methionine
Essential amino acid, precursor to cysteine and the methyl donor rSAM.
Methionine (abbreviated as Met or M) is an essential amino acid in humans, meaning it cannot be synthesized by the body and must be obtained from the diet. It was first isolated in 1921 by John Howard Mueller, and its name, an abbreviation of its structural description 2-amino-4-(methylthio)butanoic acid, was given by Satoru Odake in 1925. Methionine is encoded by the single codon AUG, which also serves as the most common start codon, signaling the initiation of protein translation from mRNA. In eukaryotes and archaea, this means methionine is typically the first amino acid incorporated into a nascent polypeptide, though it may be removed later by post-translational modification. In bacteria, the derivative N-formylmethionine is used as the initial amino acid instead. Structurally, methionine is an α-amino acid with a carboxyl group, an amino group, and an S-methyl thioether side chain, classifying it as a nonpolar, aliphatic amino acid. Along with cysteine, it is one of the two sulfur-containing proteinogenic amino acids. Unlike cysteine, methionine residues rarely have a catalytic role, though they can act as redox sensors in some cases. The thioether side chain does contribute a minor structural role through stability effects from interactions between the sulfur atom and aromatic amino acids in about one-third of known protein structures. Methionine is a precursor to both cysteine and the cofactor S-adenosylmethionine (rSAM), a pervasive methylation agent. As an essential amino acid, methionine is not synthesized de novo in humans; in plants and microorganisms, its biosynthesis belongs to the aspartate family, with the backbone derived from aspartic acid and sulfur coming from sources such as cysteine, methanethiol, or hydrogen sulfide.
- codon
- AUG
- classification
- Essential amino acid, α-amino acid, nonpolar aliphatic
- key_roles
- Precursor to cysteine and rSAM; protein synthesis initiator via N-formylmethionine-sRNA
Lore & Background
Methionine (symbol Met or M) is an essential amino acid in humans, first isolated in 1921 by John Howard Mueller and named by Satoru Odake in 1925 as an abbreviation of its structural description, 2-amino-4-(methylthio)butanoic acid. It is encoded by the single codon AUG, which also serves as the most common start codon, signaling the initiation of protein translation in eukaryotes and Archaea. As a proteinogenic α-amino acid, methionine contains a carboxyl group, an amino group, and an S-methyl thioether side chain, classifying it as nonpolar and aliphatic. It is one of only two sulfur-containing proteinogenic amino acids, alongside cysteine, though its thioether group generally lacks a catalytic role, unlike cysteine’s thiol. Methionine residues can act as redox sensors in rare cases, and the side chain sulfur participates in stabilizing S/π interactions with aromatic amino acids in about one-third of known protein structures. Replacing methionine with norleucine, a straight-chain hydrocarbon amino acid, often shows little effect, suggesting methionine’s structural role is minor. Methionine is the precursor to cysteine and the pervasive methylation cofactor S-adenosylmethionine (rSAM), which serves mainly as a methyl donor. In bacteria, the derivative N-formylmethionine is used as the initial amino acid during translation. As an essential amino acid, methionine is not synthesized in humans and must be obtained from the diet. In plants and microorganisms, its biosynthesis belongs to the aspartate family, with the backbone derived from aspartic acid and sulfur from cysteine, methanethiol, or hydrogen sulfide.
Reader's Guide
Methionine's significance lies in its essential role as a building block for proteins and as a precursor to critical molecules. It is required for protein synthesis, initiated by N-formylmethionine-sRNA, and serves as the precursor to the amino acid cysteine and the methylation agent rSAM. The methionine codon AUG is also the most common start codon, signaling the initiation of protein translation. In bacteria, the derivative N-formylmethionine is used as the initial amino acid. Methionine residues do not have a catalytic role, unlike cysteine residues, but the thioether within methionine has a minor structural role due to S/π interactions with aromatic amino acids. It has been conjectured that norleucine was present in early versions of the genetic code, but methionine intruded due to its role in rSAM. Methionine can be regenerated from homocysteine via methionine synthase, a reaction requiring vitamin B12, or via betaine-homocysteine methyltransferase.
Did You Know?
- It is one of only two amino acids encoded by a single codon (AUG) in the standard genetic code.
- Methionine is the precursor to the amino acid cysteine and the methylation agent rSAM.
- In bacteria, the derivative N-formylmethionine is used as the initial amino acid during translation.
Frequently Asked Questions
Who is Methionine?
Methionine (Met or M) is an essential, nonpolar aliphatic α-amino acid that humans cannot build internally and must pull from their diet. It occupies a singular position in biochemistry as both the universal translation-initiator and a key metabolic branch point.
What are Methionine's powers or roles?
It kicks off virtually every protein-translation event via the AUG start codon and, through N-formylmethionine-tRNA, caps the N-terminus of nascent chains. Beyond initiation, it is the direct precursor to cysteine and to S-adenosylmethionine (rSAM), the cell's dominant methyl-group donor.
How does Methionine's story end?
Once its methyl-donor duty is fulfilled, methionine is converted to homocysteine and then funneled either back into the methionine cycle or down the transsulfuration pathway into cysteine. Its carbon and sulfur skeletons are ultimately recycled into energy metabolism and other biosynthetic intermediates, so its 'ending' is really a handoff to downstream pathways.
Why is Methionine important?
Because rSAM-dependent methylation touches DNA, RNA, histones, and countless proteins, methionine availability acts as a global regulator of gene expression and signaling. Pair that with its non-negotiable role as the translation start signal, and you see why a single amino acid sits at the intersection of so many core cellular processes.
More in Cell And Molecular Biology 1-24
Spotted an error? Know more?
This is a living reference — every entry is fact-audited, and reader corrections feed straight into our audit queue. Suggest an edit · See this site's audit record