Methionine (symbol Met or M) () is an
essential amino acid
An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...
in humans. As the precursor of other amino acids such as
cysteine and
taurine
Taurine (), or 2-aminoethanesulfonic acid, is an organic compound that is widely distributed in animal tissues. It is a major constituent of bile and can be found in the large intestine, and accounts for up to 0.1% of total human body weight. I ...
, versatile compounds such as
SAM-e
''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cofactor (biochemistry), cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anaboli ...
, and the important antioxidant
glutathione
Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...
, methionine plays a critical role in the metabolism and health of many species, including humans. It is
encoded
In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form, sometimes shortened or secret, for communication through a communication ...
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
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ma ...
donor in
DNA methylation, is related to cancer growth in a number of studies.
Methionine was first isolated in 1921 by
John Howard Mueller
John Howard Mueller (June 13, 1891, Sheffield, Massachusetts – February 14, 1954) was an American biochemist, pathologist, and bacteriologist. He is known as the discoverer of the amino acid methionine in 1921, and as the co-developer, with Jane ...
.
Biochemical details
Methionine (abbreviated as Met or M; encoded by the codon AUG) is an α-
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
that is used in the
biosynthesis of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s. It contains a
carboxyl group
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
(which is in the deprotonated −COO
− form under biological
pH conditions), an
amino group
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...
(which is in the
protonated
In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid, ...
form under biological pH conditions) located in α-position with respect to the carboxyl group, and an ''S''-methyl
thioether
In organic chemistry, an organic sulfide (British English sulphide) or thioether is an organosulfur functional group with the connectivity as shown on right. Like many other sulfur-containing compounds, volatile sulfides have foul odors. A su ...
side chain, classifying it as a
nonpolar
In chemistry, polarity is a separation of electric charge leading to a molecule or its chemical groups having an electric dipole moment, with a negatively charged end and a positively charged end.
Polar molecules must contain one or more polar ...
,
aliphatic
In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, ...
amino acid.
In nuclear genes of
eukaryotes and in
Archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
, 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
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
translation
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
.
A proteinogenic amino acid
Together with
cysteine, methionine is one of two
sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
-containing
proteinogenic amino acid
Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) amino aci ...
s. 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/Ï€ 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
Norleucine (abbreviated as Nle) is an amino acid with the formula CH3(CH2)3CH(NH2)CO2H. A systematic name for this compound is 2-aminohexanoic acid. The compound is an isomer of the more common amino acid leucine. Like most other α-amino acids ...
, 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''-adenosylmethionine (SAM-e). This situation is not unique and may have occurred with ornithine and arginine.
Encoding
Methionine is one of only two amino acids encoded by a single codon (AUG) in the standard genetic code
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
(tryptophan
Tryptophan (symbol Trp or W)
is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...
, 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
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
and yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
, 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
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
from mRNA when the AUG codon is in a Kozak consensus sequence
The Kozak consensus sequence (Kozak consensus or Kozak sequence) is a nucleic acid motif that functions as the protein translation initiation site in most eukaryotic mRNA transcripts. Regarded as the optimum sequence for initiating translation in ...
. As a consequence, methionine is often incorporated into the ''N''-terminal position of protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s in eukaryotes and archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
during translation, although it can be removed by post-translational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
. In bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
, the derivative ''N''-formylmethionine is used as the initial amino acid.
Derivatives
''S''-Adenosylmethionine
The methionine-derivative ''S''-adenosylmethionine (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
In organic chemistry, a sulfonium ion, also known as sulphonium ion or sulfanium ion, is a positively-charged ion (a " cation") featuring three organic substituents attached to sulfur. These organosulfur compounds have the formula . Together wi ...
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, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...
(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''-adenosylhomocysteine 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
Autoinducer-2 (AI-2), a furanosyl borate diester or tetrahydroxy furan (species dependent), is a member of a family of signaling molecules used in quorum sensing. AI-2 is one of only a few known biomolecules incorporating boron. First identified ...
, which is excreted as a waste product or quorum signal.
Biosynthesis
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
Methanethiol (also known as methyl mercaptan) is an organosulfur compound with the chemical formula . It is a colorless gas with a distinctive putrid smell. It is a natural substance found in the blood, brain and feces of animals (including humans ...
, or hydrogen sulfide.[
* First, aspartic acid is converted via β-aspartyl semialdehyde into ]homoserine
Homoserine (also called isothreonine) is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2OH. -Homoserine is not one of the common amino acids encoded by DNA. It differs from the proteinogenic amino acid serine by insertion of an additi ...
by two reduction steps of the terminal carboxyl group (homoserine has therefore a γ-hydroxyl, hence the homo- series). The intermediate aspartate semialdehyde is the branching point with the lysine biosynthetic pathway, where it is instead condensed with pyruvate. Homoserine is the branching point with the threonine pathway, where instead it is isomerised after activating the terminal hydroxyl with phosphate (also used for methionine biosynthesis in plants).[
* Homoserine is then activated with a phosphate, succinyl or an acetyl group on the hydroxyl.
** In plants and possibly in some bacteria,][ phosphate is used. This step is shared with threonine biosynthesis.][
** In most organisms, an acetyl group is used to activate the homoserine. This can be catalysed in bacteria by an enzyme encoded by ''metX'' or ''metA'' (not homologues).][
** In ]enterobacteria
Enterobacteriaceae is a large family of Gram-negative bacteria
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their ...
and a limited number of other organisms, succinate is used. The enzyme that catalyses the reaction is MetA and the specificity for acetyl-CoA and succinyl-CoA is dictated by a single residue.[ The physiological basis for the preference of acetyl-CoA or succinyl-CoA is unknown, but such alternative routes are present in some other pathways (''e.g.'' lysine biosynthesis and arginine biosynthesis).
* The hydroxyl activating group is then replaced with cysteine, methanethiol, or hydrogen sulfide. A replacement reaction is technically a γ- elimination followed by a variant of a ]Michael addition
In organic chemistry, the Michael reaction or Michael addition is a reaction between a Michael donor (an enolate or other nucleophile) and a Michael acceptor (usually an α,β-unsaturated carbonyl) to produce a Michael adduct by creating a carbon ...
. All the enzymes involved are homologues and members of the Cys/Met metabolism PLP-dependent enzyme family
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.
Mechanism of action
PLP ...
, which is a subset of the PLP-dependent fold type I clade. They utilise the cofactor PLP (pyridoxal phosphate
Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent a ...
), which functions by stabilising carbanion intermediates.[
** If it reacts with cysteine, it produces ]cystathionine
Cystathionine is an intermediate in the synthesis of cysteine.
Cystathionine is produced by the transsulfuration pathway which converts homocysteine into cystathionine. Cystathionine is then used by the enzymes cystathionine gamma-lyase (CTH), ...
, which is cleaved to yield homocysteine
Homocysteine is a non-proteinogenic α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In th ...
. The enzymes involved are cystathionine-γ-synthase
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.:
:''O''4-succinyl-L-homoserine + L-cysteine \longrightarrow L-cystathionin ...
(encoded by ''metB'' in bacteria) and cystathionine-β-lyase
Cystathionine beta-lyase (), also commonly referred to as CBL or β-cystathionase, is an enzyme that primarily catalyzes the following α,β-elimination reaction
Thus, the substrate of this enzyme is L-cystathionine, whereas its 3 products a ...
(''metC''). Cystathionine is bound differently in the two enzymes allowing β or γ reactions to occur.[
** If it reacts with free hydrogen sulfide, it produces homocysteine. This is catalysed by ''O''-acetylhomoserine aminocarboxypropyltransferase (formerly known as ''O''-acetylhomoserine (thiol)-lyase. It is encoded by either ''metY'' or ''metZ'' in bacteria.][
** If it reacts with methanethiol, it produces methionine directly. Methanethiol is a byproduct of catabolic pathway of certain compounds, therefore this route is more uncommon.][
* If homocysteine is produced, the thiol group is methylated, yielding methionine. Two ]methionine synthase
Methionine synthase also known as MS, MeSe, MTR is responsible for the regeneration of methionine from homocysteine. In humans it is encoded by the ''MTR'' gene (5-methyltetrahydrofolate-homocysteine methyltransferase). Methionine synthase forms ...
s are known; one is cobalamin
Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...
(vitamin B12) dependent and one is independent.[
The pathway using cysteine is called the "]transsulfuration pathway
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''.
The ''forwar ...
", 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 transsulfurylation route") or from hydrogen sulfide ("direct sulfurylation route"); the activated serine is generally ''O''-acetylserine (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.
Transsulfurylation pathway
Enzymes involved in the ''E. coli'' transsulfurylation route of methionine biosynthesis:
# Aspartokinase
Aspartate kinase or aspartokinase (AK) is an enzyme that catalyzes the phosphorylation of the amino acid aspartate. This reaction is the first step in the biosynthesis of three other amino acids: methionine, lysine, and threonine, known as the "a ...
# Aspartate-semialdehyde dehydrogenase
In enzymology, an aspartate-semialdehyde dehydrogenase () is an enzyme that is very important in the biosynthesis of amino acids in prokaryotes, fungi, and some higher plants. It forms an early branch point in the metabolic pathway forming lysine, ...
# Homoserine dehydrogenase
In enzymology, a homoserine dehydrogenase () is an enzyme that catalyzes the chemical reaction
:L-homoserine + NAD(P)+ \rightleftharpoons L-aspartate 4-semialdehyde + NAD(P)H + H+
The 2 substrates of this enzyme are L-homoserine and NAD+ ...
# Homoserine ''O''-transsuccinylase
# Cystathionine-γ-synthase
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.:
:''O''4-succinyl-L-homoserine + L-cysteine \longrightarrow L-cystathionin ...
# Cystathionine-β-lyase
Cystathionine beta-lyase (), also commonly referred to as CBL or β-cystathionase, is an enzyme that primarily catalyzes the following α,β-elimination reaction
Thus, the substrate of this enzyme is L-cystathionine, whereas its 3 products a ...
# Methionine synthase
Methionine synthase also known as MS, MeSe, MTR is responsible for the regeneration of methionine from homocysteine. In humans it is encoded by the ''MTR'' gene (5-methyltetrahydrofolate-homocysteine methyltransferase). Methionine synthase forms ...
(in mammals, this step is performed by homocysteine methyltransferase
Methionine synthase also known as MS, MeSe, MTR is responsible for the regeneration of methionine from homocysteine. In humans it is encoded by the ''MTR'' gene (5-methyltetrahydrofolate-homocysteine methyltransferase). Methionine synthase forms ...
or betaine—homocysteine ''S''-methyltransferase.)
Other biochemical pathways
Although mammals cannot synthesize methionine, they can still use it in a variety of biochemical pathways:
Catabolism
Methionine is converted to ''S''-adenosylmethionine (SAM-e) by (1) methionine adenosyltransferase.
SAM-e serves as a methyl donor in many (2) methyltransferase
Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Ross ...
reactions, and is converted to ''S''-adenosylhomocysteine (SAH).
(3) Adenosylhomocysteinase
Adenosylhomocysteinase (, ''S''-adenosylhomocysteine synthase, ''S''-adenosylhomocysteine hydrolase, adenosylhomocysteine hydrolase, ''S''-adenosylhomocysteinase, SAHase, AdoHcyase) is an enzyme that converts ''S''-adenosylhomocysteine to homocys ...
cysteine.
Regeneration
Methionine can be regenerated from homocysteine via (4) methionine synthase
Methionine synthase also known as MS, MeSe, MTR is responsible for the regeneration of methionine from homocysteine. In humans it is encoded by the ''MTR'' gene (5-methyltetrahydrofolate-homocysteine methyltransferase). Methionine synthase forms ...
in a reaction that requires vitamin B12 as a cofactor.
Homocysteine can also be remethylated using glycine betaine
Trimethylglycine is an amino acid derivative that occurs in plants. Trimethylglycine was the first betaine discovered; originally it was simply called betaine because, in the 19th century, it was discovered in sugar beets. It has a sweet and umami ...
(''N'',''N'',''N''-trimethylglycine, 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.
Reverse-transulfurylation pathway: conversion to cysteine
Homocysteine can be converted to cysteine.
* (5) Cystathionine-β-synthase (an enzyme which requires the active form of vitamin B6
Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., " vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosp ...
, pyridoxal phosphate
Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent a ...
) combines homocysteine and serine to produce cystathionine
Cystathionine is an intermediate in the synthesis of cysteine.
Cystathionine is produced by the transsulfuration pathway which converts homocysteine into cystathionine. Cystathionine is then used by the enzymes cystathionine gamma-lyase (CTH), ...
. Instead of degrading cystathionine
Cystathionine is an intermediate in the synthesis of cysteine.
Cystathionine is produced by the transsulfuration pathway which converts homocysteine into cystathionine. Cystathionine is then used by the enzymes cystathionine gamma-lyase (CTH), ...
via cystathionine-β-lyase
Cystathionine beta-lyase (), also commonly referred to as CBL or β-cystathionase, is an enzyme that primarily catalyzes the following α,β-elimination reaction
Thus, the substrate of this enzyme is L-cystathionine, whereas its 3 products a ...
, as in the biosynthetic pathway, cystathionine is broken down to cysteine and α-ketobutyrate via (6) cystathionine-γ-lyase
The enzyme cystathionine γ-lyase (EC 4.4.1.1, 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 ...
.
* (7) The enzyme α-ketoacid dehydrogenase converts α-ketobutyrate to propionyl-CoA
Propionyl-CoA is a coenzyme A derivative of propionic acid. It is composed of a 24 total carbon chain (without the coenzyme, it is a 3 carbon structure) and its production and metabolic fate depend on which organism it is present in. Several diffe ...
, which is metabolized to succinyl-CoA
Succinyl-coenzyme A, abbreviated as succinyl-CoA () or SucCoA, is a thioester of succinic acid and coenzyme A.
Sources
It is an important intermediate in the citric acid cycle, where it is synthesized from α-ketoglutarate by α-ketoglutarate d ...
in a three-step process (see propionyl-CoA
Propionyl-CoA is a coenzyme A derivative of propionic acid. It is composed of a 24 total carbon chain (without the coenzyme, it is a 3 carbon structure) and its production and metabolic fate depend on which organism it is present in. Several diffe ...
for pathway).
Ethylene synthesis
This amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
is also used by plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclu ...
s for synthesis of ethylene. The process is known as the Yang
Yang may refer to:
* Yang, in yin and yang, one half of the two symbolic polarities in Chinese philosophy
* Korean yang, former unit of currency of Korea from 1892 to 1902
* YANG, a data modeling language for the NETCONF network configuration ...
cycle or the methionine cycle.
Chemical synthesis
The industrial synthesis combines acrolein, methanethiol
Methanethiol (also known as methyl mercaptan) is an organosulfur compound with the chemical formula . It is a colorless gas with a distinctive putrid smell. It is a natural substance found in the blood, brain and feces of animals (including humans ...
, and cyanide, which affords the hydantoin. Racemic
In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
methionine can also be synthesized from diethyl sodium phthalimidomalonate by alkylation with chloroethylmethylsulfide (ClCH2CH2SCH3) followed by hydrolysis and decarboxylation.
Human nutrition
Requirements
The Food and Nutrition Board of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) for essential amino acid
An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...
s 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.
Dietary sources
High levels of methionine can be found in eggs, meat, and fish; sesame seeds, Brazil nuts, and some other plant seeds; and cereal
A cereal is any Poaceae, grass cultivated for the edible components of its grain (botanically, a type of fruit called a caryopsis), composed of the endosperm, Cereal germ, germ, and bran. Cereal Grain, grain crops are grown in greater quantit ...
grains. Most fruits and vegetables contain very little. Most legume
A legume () is a plant in the family Fabaceae (or Leguminosae), or the fruit or seed of such a plant. When used as a dry grain, the seed is also called a pulse. Legumes are grown agriculturally, primarily for human consumption, for livestock f ...
s, though protein dense, are low in methionine. Proteins without adequate methionine are not considered to be complete protein
A complete protein or whole protein is a food source of protein that contains an adequate proportion of each of the nine essential amino acids necessary in the human diet.
Amino acid profile
The following table lists the optimal profile of the ...
s. For that reason, racemic methionine is sometimes added as an ingredient to pet food
Pet food is animal feed intended for consumption by pets. Typically sold in pet stores and supermarkets, it is usually specific to the type of animal, such as dog food or cat food. Most meat used for animals is a byproduct of the human food ind ...
s.
Restriction
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
Fruit fly may refer to:
Organisms
* Drosophilidae, a family of small flies, including:
** ''Drosophila'', the genus of small fruit flies and vinegar flies
** ''Drosophila melanogaster'' or common fruit fly
** '' Drosophila suzukii'' or Asian frui ...
under dietary restriction, including restriction of essential amino acid
An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...
s (EAAs), restored fertility
Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertili ...
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
Fibroblast growth factor 21 is a liver-secreted peptide hormone that in humans is encoded by the ''FGF21'' gene. Together with FGF19 ( FGF15 in rodents) and FGF23, this protein is a member of the endocrine subgroup within the fibroblast growth ...
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
An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to 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
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...
in rat liver mitochondria offering a plausible mechanism for its hepatotoxicity
Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fr ...
".
However, since methionine is an essential amino acid
An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...
, it cannot be entirely removed from animals' diets without disease or death occurring over time. For example, rats fed a diet without methionine and choline developed steatohepatitis
Steatohepatitis is a type of fatty liver disease, characterized by inflammation of the liver with concurrent fat accumulation in liver. Mere deposition of fat in the liver is termed steatosis, and together these constitute fatty liver changes.
...
(fatty liver) and anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
, 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.
Health
Loss of methionine has been linked to senile greying of hair. Its lack leads to a buildup of hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%†...
in hair follicles, a reduction in tyrosinase
Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxy ...
effectiveness, and a gradual loss of hair color. Methionine raises the intracellular concentration of glutathione
Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...
, 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
Taurine (), or 2-aminoethanesulfonic acid, is an organic compound that is widely distributed in animal tissues. It is a major constituent of bile and can be found in the large intestine, and accounts for up to 0.1% of total human body weight. I ...
, lecithin, phosphatidylcholine
Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup.
They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soybea ...
, and other phospholipids. Improper conversion of methionine can lead to atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...
due to accumulation of homocysteine
Homocysteine is a non-proteinogenic α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In th ...
.
Other uses
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
The giant swallowtail (''Papilio cresphontes'') is the largest butterfly in North America. It is abundant through many parts of eastern North America; populations from western North America and down into Panama are now (as of 2014) considered t ...
caterpillars, which are a serious pest to orange crops.
See also
* Allantoin
Allantoin is a chemical compound with formula C4H6N4O3. It is also called 5-ureidohydantoin or glyoxyldiureide. It is a diureide of glyoxylic acid. Allantoin is a major metabolic intermediate in most organisms including animals, plants and bacter ...
* Formylmethionine
''N''-Formylmethionine (fMet, HCO-Met, For-Met) is a derivative of the amino acid methionine in which a formyl group has been added to the amino group. It is specifically used for initiation of protein synthesis from bacterial and organellar g ...
* Methionine oxidation
Methionine sulfoxide is the organic compound with the formula CH3S(O)CH2CH2CH(NH2)CO2H. It is an amino acid that occurs naturally although it is formed post-translationally.
Oxidation of the sulfur of methionine results in methionine sulfoxide o ...
* Paracetamol poisoning
Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These include ...
* Photoreactive methionine
* ''S''-Methylcysteine
References
External links
*
{{Authority control
Proteinogenic amino acids
Glucogenic amino acids
Sulfur amino acids
Thioethers
Essential amino acids