Methionine

Methionine
IUPAC name Methionine
Other names 2-amino-4-(methylthio)butanoic acid
Identifiers
Abbreviations	Met, M
CAS number	59-51-8 Y, 63-68-3 (L-isomer) Y, 348-67-4 (D-isomer) Y
PubChem	876
ChemSpider	853 Y, 5907 (L-isomer)
UNII	73JWT2K6T3 Y
EC-number	200-432-1
KEGG	D04983 N
ChEBI	CHEBI:16811 N
ChEMBL	CHEMBL42336 N
ATC code	V03AB26,QA05BA90, QG04BA90
Jmol-3D images	Image 1 Image 2
SMILES CSCCC(C(=O)O)N CSCCC(C(=O)O)N
InChI InChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8) Y Key: FFEARJCKVFRZRR-UHFFFAOYSA-N Y InChI=1/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)
Properties[2]
Molecular formula	C5H11NO2S
Molar mass	149.21 g mol−1
Appearance	White crystalline powder
Density	1.340 g/cm3
Melting point	281 °C decomp.
Solubility in water	Soluble
Acidity (pKa)	2.28 (carboxyl), 9.21 (amino)[1]
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Methionine ( /mɛˈθaɪ.ɵniːn/ or /mɛˈθaɪ.ɵnɪn/; abbreviated as Met or M)^[3] 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.^[4]

The Yang cycle

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.^[5]

Betaines

(S)-Methionine (left) and (R)-methionine (right) in zwitterionic form at neutral pH

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.^[6]

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)

Methionine biosynthesis

Other biochemical pathways

Fates of methionine

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 in a reaction that requires Vitamin B₁₂ as a cofactor.

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.^[7]

Dietary sources

Food sources of Methionine^[8]

Food	g/100g
Egg, white, dried, powder, glucose reduced	3.204
Sesame seeds flour (low fat)	1.656
Brazil nuts	1.008
Soy protein concentrate	0.814
Chicken, broilers or fryers, roasted	0.801
Fish, tuna, light, canned in water, drained solids	0.755
Wheat germ	0.456
Oat	0.312
Peanuts	0.309
Chickpea	0.253
Corn, yellow	0.197
Almonds	0.151
Beans, pinto, cooked	0.117
Lentils, cooked	0.077
Rice, brown, medium-grain, cooked	0.052

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,^[9] 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.^[10]

Methionine restriction

There is a growing body of evidence that shows restricting methionine consumption can increase lifespans in some animals.^[11]

A 2005 study showed methionine restriction without energy restriction extends mouse lifespan.^[12]

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.^[13][14]

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.^[15]

Methionine is allowed as a supplement to organic poultry feed under the US certified organic program.^[16]

See also

• Allantoin
• Formylmethionine
• Paracetamol poisoning - A Methionine-Paracetamol preparation that might prevent hepatotoxicity.
• Photo-reactive methionine

References

1. ^ Dawson, R.M.C., et al., Data for Biochemical Research, Oxford, Clarendon Press, 1959.
2. ^ Weast, Robert C., ed (1981). CRC Handbook of Chemistry and Physics (62nd ed.). Boca Raton, FL: CRC Press. p. C-374. ISBN 0-8493-0462-8. .
3. ^ "Nomenclature and symbolism for amino acids and peptides (IUPAC-IUB Recommendations 1983)", Pure Appl. Chem. 56 (5): 595–624, 1984, doi:10.1351/pac198456050595 .
4. ^ Refsum H, Ueland PM, Nygård O, Vollset SE. Homocysteine and cardiovascular disease. Annual review of medicine, 1998, 49(1), pp.31-62.
5. ^ Oz HS, Chen TS, Neuman M (2008), "Methionine deficiency and hepatic injury in a dietary steatohepatitis model", Digestive Diseases and Sciences 53 (3): 767–776, doi:10.1007/s10620-007-9900-7, PMC 2271115, PMID 17710550, http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2271115. 
6. ^ Lehninger, Albert L.; Nelson, David L.; Cox, Michael M. (2000), Principles of Biochemistry (3rd ed.), New York: W. H. Freeman, ISBN 1-57259-153-6 .
7. ^ Barger, G.; Weichselbaum, T. E. (1934), "dl-Methionine", Org. Synth. 14: 58, http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV2P0384 ; Coll. Vol. 2: 384 .
8. ^ National Nutrient Database for Standard Reference, U.S. Department of Agriculture, http://www.nal.usda.gov/fnic/foodcomp/search/, retrieved 2009-09-07 .
9. ^ Nutritional Value – Idaho Bean Commission
10. ^ What's in your dog's food?, Ojibwa Yorkies, ISBN 087605467X, http://www.yorkshire-terrier.com/dogfood.htm, retrieved 2009-09-07 .
11. ^ Alleyne, Richard (2009-12-03). "Vegetarian low protein diet could be key to long life". The Daily Telegraph (London). http://www.telegraph.co.uk/health/healthnews/6710896/Vegetarian-low-protein-diet-could-be-key-to-long-life.html. Retrieved 2010-05-12. 
12. ^ 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 .
13. ^ Grandison, R. C.; Piper, M. D. W.; Partridge, L. (2009). "Amino acid imbalance explains extension of lifespan by dietary restriction in Drosophila". Nature 462 (7276): 1061–1064. Bibcode 2009Natur.462.1061G. doi:10.1038/nature08619. PMC 2798000. PMID 19956092. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2798000. Lay summary.  edit
14. ^ http://www.sciencenews.org/view/generic/id/50275/title/Amino_acid_recipe_could_be_right_for_long_life
15. ^ Burn Baby Burn! Grass Burns from Dog Urine, About.Com, http://dogs.about.com/od/dogcarebasics/qt/grass_burns.htm, retrieved 2010-02-15 .
16. ^ Federal Register, US, http://edocket.access.gpo.gov/2011/2011-5716.htm, retrieved 2011-03-12 .

• Rudra, M. N.; Chowdhury, L. M. (30 September 1950), "Methionine Content of Cereals and Legumes", Nature 166 (568): 568, doi:10.1038/166568a0 

External links

• Food Sources of Methionine
• Foods containing methionine