Skeletal formula of the canonical form of methionine
| IUPAC name |
|Other names |
3D model (JSmol)
CompTox Dashboard (EPA)
|Molar mass||149.21 g·mol−1|
|Appearance||White crystalline powder|
|Melting point||281 °C (538 °F; 554 K) decomposes|
|Acidity (pKa)||2.28 (carboxyl), 9.21 (amino)|
|V03AB26 ( WHO ) QA05BA90 ( WHO ), QG04BA90 ( WHO )|
|Supplementary data page|
|Methionine (data page)|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Methionine (symbol Met or M) // ) is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical role in the metabolism and health of many species, including humans. It is encoded by the codon AUG.(
Methionine is also an important part of angiogenesis, the growth of new blood vessels. Supplementation may benefit those suffering from copper poisoning.Overconsumption of methionine, the methyl group donor in DNA methylation, is related to cancer growth in a number of studies. Methionine was first isolated in 1921 by John Howard Mueller.
Methionine (abbreviated as Met or M; encoded by the codon AUG) is an α-amino acid that is used in the biosynthesis of proteins. It contains a carboxyl group (which is in the deprotonated −COO− form under biological pH conditions), an amino group (which is in the protonated −NH3+ form under biological pH conditions) located in α-position with respect to the carboxyl group, and an S-methyl thioether side chain, classifying it as a nonpolar, aliphatic amino acid.
In nuclear genes of eukaryotes and in Archaea, methionine is coded for by the start codon, meaning it indicates the start of the coding region and is the first amino acid produced in a nascent polypeptide during mRNA translation.
Together with cysteine, methionine is one of two sulfur-containing proteinogenic amino acids. Excluding the few exceptions where methionine may act as a redox sensor (e.g.,), methionine residues do not have a catalytic role. This is in contrast to cysteine residues, where the thiol group has a catalytic role in many proteins. The thioether does however have a minor structural role due to the stability effect of S/π interactions between the side chain sulfur atom and aromatic amino acids in one-third of all known protein structures. This lack of a strong role is reflected in experiments where little effect is seen in proteins where methionine is replaced by norleucine, a straight hydrocarbon sidechain amino acid which lacks the thioether. It has been conjectured that norleucine was present in early versions of the genetic code, but methionine intruded into the final version of the genetic code due to the fact it is used in the cofactor S-adenosyl methionine (SAM-e). This situation is not unique and may have occurred with ornithine and arginine.
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). In reflection to the evolutionary origin of its codon, the other AUN codons encode isoleucine, which is also a hydrophobic amino acid. In the mitochondrial genome of several organisms, including metazoa and yeast, the codon AUA also encodes for methionine. In the standard genetic code AUA codes for isoleucine and the respective tRNA (ileX in Escherichia coli) uses the unusual base lysidine (bacteria) or agmatidine (archaea) to discriminate against AUG.
The methionine codon AUG is also the most common start codon. A "Start" codon is 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.
The methionine-derivative S-adenosyl methionine (SAM-e) is a cofactor that serves mainly as a methyl donor. SAM-e is composed of an adenosyl molecule (via 5' carbon) attached to the sulfur of methionine, therefore making it a sulfonium cation (i.e., three substituents and positive charge). The sulfur acts as a soft Lewis acid (i.e., donor/electrophile) which allows the S-methyl group to be transferred to an oxygen, nitrogen, or aromatic system, often with the aid of other cofactors such as cobalamin (vitamin B12 in humans). Some enzymes use SAM-e to initiate a radical reaction; these are called radical SAM-e enzymes. As a result of the transfer of the methyl group, S-adenosyl-homocysteine is obtained. In bacteria, this is either regenerated by methylation or is salvaged by removing the adenine and the homocysteine, leaving the compound dihydroxypentandione to spontaneously convert into autoinducer-2, which is excreted as a waste product / quorum signal.
As an essential amino acid, methionine is not synthesized de novo in humans and other animals, which must ingest methionine or methionine-containing proteins. In plants and microorganisms, methionine biosynthesis belongs to the aspartate family, along with threonine and lysine (via diaminopimelate, but not via α-aminoadipate). The main backbone is derived from aspartic acid, while the sulfur may come from cysteine, methanethiol, or hydrogen sulfide.
The pathway using cysteine is called the "transsulfuration pathway", while the pathway using hydrogen sulfide (or methanethiol) is called "direct-sulfurylation pathway".
Cysteine is similarly produced, namely it can be made from an activated serine and either from homocysteine ("reverse trans-sulfurylation route") or from hydrogen sulfide ("direct sulfurylation route"); the activated serine is generally O-acetyl-serine (via CysK or CysM in E. coli), but in Aeropyrum pernix and some other archaea O-phosphoserine is used.CysK and CysM are homologues, but belong to the PLP fold type III clade.
Enzymes involved in the E. coli trans-sulfurylation route of methionine biosynthesis:
Although mammals cannot synthesize methionine, they can still use it in a variety of biochemical pathways:
Methionine is converted to S-adenosylmethionine (SAM-e) by (1) methionine adenosyltransferase.
SAM-e serves as a methyl-donor in many (2) methyltransferase reactions, and is converted to S-adenosylhomocysteine (SAH).
(3) Adenosylhomocysteinase cysteine.
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.220.127.116.11, 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.
Homocysteine can be converted to cysteine.
This amino acid is also used by plants for synthesis of ethylene. The process is known as the Yang cycle or the methionine cycle.
The industrial synthesis combines acrolein, methanethiol, and cyanide, which affords the hydantoin.Racemic methionine can also be synthesized from diethyl sodium phthalimidomalonate by alkylation with chloroethylmethylsulfide (ClCH2CH2SCH3) followed by hydrolysis and decarboxylation.
The Food and Nutrition Board of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) for essential amino acids in 2002. For methionine combined with cysteine, for adults 19 years and older, 19 mg/kg body weight/day.
This translates to about 1.33 grams per day for a 70 kilogram individual.
|Egg, white, dried, powder, glucose reduced||3.204|
|Sesame seeds flour (low fat)||1.656|
|Cheese, Parmesan, shredded||1.114|
|hemp seed, hulled||0.933|
|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|
|Egg, whole, cooked, hard-boiled||0.392|
|Beans, pinto, cooked||0.117|
|Rice, brown, medium-grain, cooked||0.052|
High levels of methionine can be found in eggs, meat, and fish; sesame seeds, Brazil nuts, and some other plant seeds; and cereal grains. Most fruits and vegetables contain very little. Most legumes, though protein dense, are low in methionine. Proteins without adequate methionine are not considered to be complete proteins.For that reason, racemic methionine is sometimes added as an ingredient to pet foods.
Some scientific evidence indicates restricting methionine consumption can increase lifespans in fruit flies.
A 2005 study showed methionine restriction without energy restriction extends mouse lifespans.This extension requires intact growth hormone signaling, as animals without intact growth-hormone signaling do not have a further increase in lifespan when methionine restricted. The metabolic response to methionine restriction is also altered in mouse growth hormone signaling mutants.
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."Restoring methionine to the diet of mice on a dietary restriction regimen blocks many acute benefits of dietary restriction, a process that may be mediated by increased production of hydrogen sulfide.
Methionine restriction can increase circulating liver hormone FGF21 between 5-fold and 10-fold in mice.Several studies showed that methionine restriction also inhibits aging-related disease processes in mice and inhibits colon carcinogenesis in rats. In humans, methionine restriction through dietary modification could be achieved through a plant-based diet.
Restriction of dietary methionine reduces levels of its catabolite S-adenosylmethionine (SAM-e), resulting is a subsequent loss of histone methylation.An active process mediated by a specific, preserved methylation of H3K9 preserves the memory of the original methylation profile, allowing the epigenome to be restored when dietary methionine levels return.
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 cannot be entirely removed from animals' diets without disease or death occurring over time.[ citation needed ] For example, rats fed a diet without methionine and choline developed steatohepatitis (fatty liver) and anemia, and lost two-thirds of their body weight over 5 weeks. Administration of methionine ameliorated the pathological consequences of methionine deprivation. Short-term removal of only methionine from the diet can reverse diet-induced obesity and promotes insulin sensitivity in mice, and methionine restriction also protects a mouse model of spontaneous, polygenic obesity and diabetes.
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.Methionine raises the intracellular concentration of glutathione, thereby promoting antioxidant mediated cell defense and redox regulation. It also protects cells against dopamine induced nigral cell loss by binding oxidative metabolites.
Methionine is an intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and other phospholipids. Improper conversion of methionine can lead to atherosclerosisdue to accumulation of homocysteine.
DL-Methionine is sometimes given as a supplement to dogs; It helps reduce the chances of kidney stones in dogs. Methionine is also known to increase the urinary excretion of quinidine by acidifying the urine. Aminoglycoside antibiotics used to treat urinary tract infections work best in alkaline conditions, and urinary acidification from using methionine can reduce its effectiveness. If a dog is on a diet that acidifies the urine, methionine should not be used.
Methionine is allowed as a supplement to organic poultry feed under the US certified organic program.
Methionine can be used as a nontoxic pesticide option against giant swallowtail caterpillars, which are a serious pest to orange crops.
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula HOOC-CH-(NH2)-CH2-SH. The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
Isoleucine is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, an α-carboxylic acid group, and a hydrocarbon side chain with a branch. It is classified as a non-polar, uncharged, branched-chain, aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it, and must be ingested in our diet. Isoleucine is synthesized from pyruvate employing leucine biosynthesis enzymes in other organisms such as bacteria. It is encoded by the codons AUU, AUC, and AUA.
Threonine is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, a carboxyl group, and a side chain containing a hydroxyl group, making it a polar, uncharged amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Threonine is synthesized from aspartate in bacteria such as E. coli. It is encoded by all the codons starting AC.
Homocystinuria or HCU is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. It is an inherited autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from both parents to be affected. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate.
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism.
Homoserine (also called isothreonine) is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2OH. l-Homoserine is not one of the common amino acids encoded by DNA. It differs from the proteinogenic amino acid serine by insertion of an additional -CH2- unit into the backbone. Homoserine, or its lactone form, is the product of a cyanogen bromide cleavage of a peptide by degradation of methionine.
Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can only synthesize 11 of the 20 standard amino acids, and in time of accelerated growth, histidine can be considered an essential amino acid.
Cystathionine-β-synthase, also known as CBS, is an enzyme (EC 18.104.22.168) that in humans is encoded by the CBS gene. It catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine:
Cystathionine is an intermediate in the synthesis of cysteine.
The enzyme cystathionine γ-lyase (EC 22.214.171.124, CTH or CSE; also cystathionase; systematic name L-cystathionine cysteine-lyase (deaminating; 2-oxobutanoate-forming)) breaks down cystathionine into cysteine, 2-oxobutanoate (α-ketobutyrate), and ammonia:
The transsulfuration pathway is a metabolic pathway involving the interconversion of cysteine and homocysteine through the intermediate cystathionine. Two transsulfurylation pathways are known: the forward and the reverse.
Cystathionine beta-lyase, also commonly referred to as CBL or β-cystathionase, is an enzyme that primarily catalyzes the following α,β-elimination reaction
The enzyme methionine γ-lyase (EC 126.96.36.199, MGL) is in the γ-family of PLP-dependent enzymes. It degrades sulfur-containing amino acids to α-keto acids, ammonia, and thiols:
In enzymology, a cystathionine gamma-synthase is an enzyme that catalyzes the formation of cystathionine from cysteine and an activated derivative of homoserine, e.g.:
In enzymology, an O-acetylhomoserine aminocarboxypropyltransferase is an enzyme that catalyzes the chemical reaction
Methionine synthase reductase, also known as MSR, is an enzyme that in humans is encoded by the MTRR gene.
In molecular biology, the Cys/Met metabolism PLP-dependent enzyme family is a family of proteins including enzymes involved in cysteine and methionine metabolism which use PLP (pyridoxal-5'-phosphate) as a cofactor.
A low-sulfur diet is a diet with reduced sulfur content. Important dietary sources of sulfur and sulfur containing compounds may be classified as essential mineral, essential amino acid (methionine) and semi-essential amino acid.
In biochemistry, non-coded or non-proteinogenic amino acids are distinct from the 22 proteinogenic amino acids which are naturally encoded in the genome of organisms for the assembly of proteins. However, over 140 non-proteinogenic amino acids occur naturally in proteins and thousands more may occur in nature or be synthesized in the laboratory. Many non-proteinogenic amino acids are important:
L-Aspartic-4-semialdehyde is an α-amino acid derivative of aspartate. It is an important intermediate in the aspartate pathway, which is a metabolic pathway present in bacteria and plants. The aspartate pathway leads to the biosynthesis of a variety of amino acids from aspartate, including lysine, methionine, and threonine.