|CAS number||, (L-isomer) , (D-isomer)|
|ATC code||V03,QA05, QG04|
|Jmol-3D images||Image 1
|Molar mass||149.21 g mol−1|
|Appearance||White crystalline powder|
|Melting point||281 °C decomp.|
|Solubility in water||Soluble|
|Acidity (pKa)||2.28 (carboxyl), 9.21 (amino)|
|Supplementary data page|
|n, εr, etc.|
Solid, liquid, gas
|Spectral data||UV, IR, NMR, MS|
| (what is: / ?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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 initiation codon AUG which indicates mRNA's coding region where translation into protein begins.
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.
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 most common eukaryote "Start" message for a ribosome that signals the initiation of protein translation from mRNA when the AUG codon is in a Kozak consensus sequence. As a consequence, methionine is often incorporated into the N-terminal position of proteins in eukaryotes and archaea during translation, although it can be removed by post-translational modification. In bacteria, the derivative N-formylmethionine is used as the initial amino acid.
Loss of methionine has been linked to senile greying of hair. Its lack leads to a buildup of hydrogen peroxide in hair follicles, a reduction in tyrosinase effectiveness and a gradual loss of hair color. 
As an essential amino acid, methionine is not synthesized de novo in humans, who 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:
- Homoserine dehydrogenase
- Homoserine O-transsuccinylase
- Methionine synthase (in mammals, this step is performed by Homocysteine methyltransferase or Betaine—homocysteine S-methyltransferase)
Other biochemical pathways
Although mammals cannot synthesize methionine, they can still use it in a variety of biochemical pathways:
Generation of homocysteine
There are two fates of homocysteine: it can be used to regenerate methionine, or to form cysteine.
Regeneration of methionine
Homocysteine can also be remethylated using glycine betaine (NNN-trimethyl glycine, TMG) to methionine via the enzyme betaine-homocysteine methyltransferase (E.C.18.104.22.168, 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).
|Egg, white, dried, powder, glucose reduced||3.204|
|Sesame seeds flour (low fat)||1.656|
|Egg, whole, dried||1.477|
|Cheese, Parmesan, shredded||1.114|
|Soy protein concentrate||0.814|
|Chicken, broilers or fryers, roasted||0.801|
|Fish, tuna, light, canned in water, drained solids||0.755|
|Beef, cured, dried||0.749|
|Beef, ground, 95% lean meat / 5% fat, raw||0.565|
|Pork, ground, 96% lean / 4% fat, raw||0.564|
|Beans, pinto, cooked||0.117|
|Rice, brown, medium-grain, cooked||0.052|
High levels of methionine can be found in eggs, 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. Racemic methionine is sometimes added as an ingredient to pet foods.
There is scientific evidence that 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 the diet of fruit flies under dietary restriction, including restriction of essential amino acids (EAAs), restored fertility without reducing the longer lifespans that are typical of dietary restriction, leading the researchers to determine that methionine “acts in combination with one or more other EAAs to shorten lifespan.”
A 2009 study on rats showed "methionine supplementation in the diet specifically increases mitochondrial ROS production and mitochondrial DNA oxidative damage in rat liver mitochondria offering a plausible mechanism for its hepatotoxicity".
However, since methionine is an essential amino acid, it should not be entirely removed from animals' diets without disease or death occurring over time. For example, rats fed a diet without methionine developed steatohepatitis (fatty liver), anemia and lost two thirds of their body weight over 5 weeks. Administration of methionine ameliorated the pathological consequences of methionine deprivation.
Methionine is allowed as a supplement to organic poultry feed under the US certified organic program.
- Methionine oxidation
- Paracetamol poisoning - A Methionine-Paracetamol preparation that might prevent hepatotoxicity.
- Photo-reactive methionine
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- Wood, J.M., et al. (2009). Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair. FASEB J. 2009 Jul;23(7):2065-75. doi: 10.1096/fj.08-125435. Epub 2009 Feb 23.
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- Miller, Richard A.; Buehner, Gretchen; Chang, Yayi; Harper, James M.; Sigler, Robert; Smith-Wheelock, Michael (2005). "Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance". Aging cell 4 (3): 119–125. doi:10.1111/j.1474-9726.2005.00152.x. PMID 15924568..
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- Life-Span Extension in Mice by Preweaning Food Restriction and by Methionine Restriction in Middle Age
- Komninou, Despina; Leutzinger, Yvonne; Reddy, Bandaru S.; Richie Jr., John P. (2006). "Methionine Restriction Inhibits Colon Carcinogenesis". Nutrition and Cancer 54 (2): 202–8. doi:10.1207/s15327914nc5402_6. PMID 16898864.
- Gomez, J; Caro, P; Sanchez, I; Naudi, A; Jove, M; Portero-Otin, M; Lopez-Torres, M; Pamplona, R et al. (2009). "Effect of methionine dietary supplementation on mitochondrial oxygen radical generation and oxidative DNA damage in rat liver and heart". Journal of bioenergetics and biomembranes 41 (3): 309–21. doi:10.1007/s10863-009-9229-3. PMID 19633937.
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- Food Sources of Methionine
- Foods containing methionine