View source for Methionine

{{NatOrganicBox
|image=[[Image:Methionin - Methionine.svg|200px]] [[Image:L-methionine-B-3D-balls.png|180px]]
Chemical structure of Methionine
|name= (''S'')-2-amino-4-(methylsulfanyl)-butanoic acid
|OtherNames = Met, M
|PubChem=876
|CAS=63-68-3
|SMILES=CSCC[C@H](N)C(O)=O
|C=5 |H=11 |N=1 |O=2 |S=1
|mass=149.21 g/mol
}}
{{CMG}}



'''Methionine''' (abbreviated as '''Met''' or '''M''')<ref>{{cite web | author=IUPAC-IUBMB Joint Commission on Biochemical Nomenclature | title=Nomenclature and Symbolism for Amino Acids and Peptides | work=Recommendations on Organic & Biochemical Nomenclature, Symbols & Terminology etc | url=http://www.chem.qmul.ac.uk/iupac/AminoAcid/ | accessdate=2007-05-17}}</ref> is an α-[[amino acid]] with the [[chemical formula]] HO<sub>2</sub>CCH(NH<sub>2</sub>)CH<sub>2</sub>CH<sub>2</sub>SCH<sub>3</sub>. This [[Essential amino acid|essential amino acid]] is classified as [[nonpolar]]. 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 [[phospholipid]]s. 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 significant, in that it carries the "Start" message for a [[ribosome]] that signals the initiation of protein [[Translation (biology)|translation]] from mRNA. As a consequence, methionine is incorporated into the N-terminal position of all [[protein]]s in [[eukaryote]]s and [[archaea]] during translation, although it is usually removed by [[post-translational modification]].

== Biosynthesis ==
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 [[folic acid|folates]] affords methionine.  Both [[cystathionine-γ-synthase]] and [[cystathionine-β-lyase]] require [[Pyridoxal-phosphate|Pyridoxyl-5'-phosphate]] as a [[cofactor]], whereas [[homocysteine methyltransferase]] requires [[Cyanocobalamin|Vitamin B12]] as a cofactor.<ref>Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6.</ref> 

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]])

[[Image:Met biosynthesis.gif|left|500px]]

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

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]]:  
* Methionine can be regenerated from homocysteine via (4) [[methionine synthase]].  It can also be remethylated using [[glycine betaine]] (NNN-trimethyl glycine) 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 sythase.  
* 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) [[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).

[[Image:Met pathway.gif|Fates of methionine|right|450px]]

==Synthesis==
[[Racemic]] methionine can be synthesized from diethyl sodium phthalimidomalonate by alkylation with chloroethylmethylsulfide (ClCH<sub>2</sub>CH<sub>2</sub>SCH<sub>3</sub>) followed by hydrolysis and decarboxylation.<ref>{{OrgSynth | author = Barger, G.; Weichselbaum, T. E. | title = dl-Methionine | | collvol = 2 | collvolpages = 384 | year = 1943 | prep = CV2P0384}}</ref>

==Dietary aspects==
High levels of methionine can be found in sesame seeds, Brazil nuts, fish, meats, and some other plant seeds. Most fruit and vegetables contain very little; however, some have significant amounts, such as spinach, potatoes, and boiled corn.st DL-methionine is sometimes added as an ingredient to [[pet food]]s.<ref>[http://www.yorkshire-terrier.com/dogfood.htm What's in your dog's food?]</ref> Methionine, cysteine, and soy protein heated in a small amount of water creates a meat-like aroma.

== See also ==
* [[Allantoin]]
* [[Formylmethionine]]
* [[Paracetamol#Prevention|Paradote]] - A Methionine-Paracetamol preparation that might prevent hepatotoxicity.
* [[Photo-reactive amino acid analog|Photo-reactive methionine]]

==References==
{{Reflist}}

==External links==
* [http://www.hcusupport.com/diet.htm Foods containing methionine]
* [http://www.compchemwiki.org/index.php?title=Methionine Computational Chemistry Wiki]

{{AminoAcids}}
{{Antidotes}}

[[Category:Proteinogenic amino acids]]
[[Category:Glucogenic amino acids]]
[[Category:Sulfur amino acids]]
[[Category:Thioethers]]
[[Category:Essential amino acids]]

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