Methionine

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Methionine
Methionin - Methionine.svg
Ball-and-stick model of the L-isomer
Identifiers
Abbreviations Met, M
CAS number 59-51-8 YesY, 63-68-3 (L-isomer) YesY, 348-67-4 (D-isomer) YesY
PubChem 876
ChemSpider 853 YesY, 5907 (L-isomer)
UNII 73JWT2K6T3 YesY
EC-number 200-432-1
KEGG D04983 YesY
ChEBI CHEBI:16811 YesY
ChEMBL CHEMBL42336 N
ATC code V03AB26,QA05BA90, QG04BA90
Jmol-3D images Image 1
Image 2
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
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

Methionine (/mɛˈθ.ɵnn/ or /mɛˈθ.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 initiation codon AUG which indicates mRNA's coding region where translation into protein begins.

Function[edit]

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 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. [5]

Zwitterions[edit]

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

Biosynthesis[edit]

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.[6]

Enzymes involved in methionine biosynthesis:

  1. Aspartokinase
  2. 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 or Betaine—homocysteine S-methyltransferase)
Methionine biosynthesis

Other biochemical pathways[edit]

Fates of methionine

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

Generation of homocysteine[edit]

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[edit]

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[edit]

Homocysteine can be converted to cysteine.

Synthesis[edit]

Racemic methionine can be synthesized from diethyl sodium phthalimidomalonate by alkylation with chloroethylmethylsulfide (ClCH2CH2SCH3) followed by hydrolysis and decarboxylation.[7]

Dietary sources[edit]

Food sources of Methionine[8]
Food g/100g
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
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
Beef, cured, dried 0.749
Bacon 0.593
Beef, ground, 95% lean meat / 5% fat, raw 0.565
Pork, ground, 96% lean / 4% fat, raw 0.564
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 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. However, it is the combination of methionine + cystine which is considered for completeness of a protein. (Source: Nutritiondata.com) Racemic methionine is sometimes added as an ingredient to pet foods.[9]

Methionine restriction[edit]

There is scientific evidence that restricting methionine consumption can increase lifespans in some animals.[10]

A 2005 study showed methionine restriction without energy restriction extends mouse lifespan.[11]

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.”[12][13]

Several studies showed that methionine restriction also inhibits aging-related disease processes in mice[14][15] and inhibits colon carcinogenesis in rats.[16] In humans, methionine restriction through dietary modification could be achieved through a vegan diet. Veganism being a completely plant based diet is typically very low in methionine, however certain nuts and legumes may provide higher levels.[17]

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".[18]

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.[19]

Methionine might also be essential to reversing damaging methylation of glucocorticoid receptors caused by repeated stress exposures, with implications for depression.[20]

Other uses[edit]

DL-Methionine is sometimes given as a supplement to dogs; it helps keep dogs from damaging grass by reducing the pH of the urine.[21][unreliable source?]

Methionine is allowed as a supplement to organic poultry feed under the US certified organic program.[22]

See also[edit]

References[edit]

  1. ^ Dawson, R.M.C. et al. (1959). Data for Biochemical Research. Oxford: Clarendon Press. 
  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), 1984: 595–624, doi:10.1351/pac198456050595 
  4. ^ Refsum H, Ueland PM, Nygård O, Vollset SE; Ueland; Nygård; Vollset (1998). "Homocysteine and Cardiovascular Disease". Annual review of medicine 49 (1): 31–62. doi:10.1146/annurev.med.49.1.31. 
  5. ^ 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.
  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 ; Coll. Vol. 2: 384 
  8. ^ National Nutrient Database for Standard Reference. U.S. Department of Agriculture. Retrieved 2009-09-07 .
  9. ^ Liz Palika. New York: Howell Book House. 1996. ISBN 0-87605-467-X. 
  10. ^ Alleyne, Richard (2009-12-03). "Vegetarian low protein diet could be key to long life". The Daily Telegraph (London). Retrieved 2010-05-12. 
  11. ^ 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. .
  12. ^ 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. Lay summary.  edit
  13. ^ "Amino acid recipe could be right for long life". Science News. December 2, 2009. 
  14. ^ Richie Jr, JP; Leutzinger, Y; Parthasarathy, S; Malloy, V; Orentreich, N; Zimmerman, JA (1994). "Methionine restriction increases blood glutathione and longevity in F344 rats". FASEB journal : official publication of the Federation of American Societies for Experimental Biology 8 (15): 1302–7. PMID 8001743. 
  15. ^ Life-Span Extension in Mice by Preweaning Food Restriction and by Methionine Restriction in Middle Age
  16. ^ 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. 
  17. ^ Cavuoto, Paul, and Michael F. Fenech. "A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension." Cancer treatment reviews 38.6 (2012): 726-736.
  18. ^ 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. 
  19. ^ 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. 
  20. ^ http://www.ncbi.nlm.nih.gov/pubmed/16306417?dopt=Abstract&holding=npg
  21. ^ "Burn Baby Burn! Grass Burns from Dog Urine". About.Com. Retrieved 2010-02-15 
  22. ^ Federal Register. US. Retrieved 2011-03-12 .

External links[edit]