Editing Methionine

{{Short description|Sulfur-containing amino acid}}
{{chembox
| Name           = Methionine
| ImageFile      = Methionin - Methionine.svg
| ImageName      = Chemical structure of methionine
| ImageCaption   = [[Skeletal formula]] of the canonical form of methionine
| ImageFileL2    = Methionine-from-xtal-3D-bs-17.png
| ImageSizeL2    = 120px
| ImageCaptionL2 = [[Ball-and-stick model]]
| ImageFileR2    = L-methionine-from-xtal-Mercury-3D-sf.png
| ImageSizeR2    = 120px
| ImageCaptionR2 = [[Space-filling model]]
| IUPACName      = Methionine
| OtherNames     = 2-amino-4-(methylthio)butanoic acid<br>Amino-γ-methylthiobutyric acid
| SystematicName = 2-Amino-4-(methylsulfanyl)butanoic acid
| Section1       = {{Chembox Identifiers
| index1_label = D/L
| index2_label = D
| index_label = L <!-- needs to be L (natural isomer) so drugbank etc. take correct index_label -->
| Abbreviations = Met, M
| UNII1_Ref = {{fdacite|correct|FDA}}
| UNII1 = 73JWT2K6T3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = AE28F7PNPL
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = 868496F25R
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 42336
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C00073
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FFEARJCKVFRZRR-BYPYZUCNSA-N
| InChIKey1 = FFEARJCKVFRZRR-UHFFFAOYSA-N
| InChIKey2 = FFEARJCKVFRZRR-SCSAIBSYSA-N
| CASNo1 = 59-51-8
| CASNo1_Ref = {{cascite|correct|CAS}}
| CASNo = 63-68-3
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo2 = 348-67-4
| CASNo2_Ref = {{cascite|correct|CAS}}
| EC_number = 200-432-1
| ChemSpiderID1_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID1 = 853
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5907
| ChemSpiderID2_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID2 =76512
| PubChem = 6137
| PubChem1 = 876
| PubChem2 = 84815
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16643
| ChEBI1_Ref = {{ebicite|correct|EBI}}
| ChEBI1 = 16811
| ChEBI2_Ref = {{ebicite|correct|EBI}}
| ChEBI2 = 16867
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00134
| SMILES = CSCC[C@H](N)C(=O)O
| SMILES3 = CSCC[C@H]([NH3+])C(=O)[O-]
| SMILES3_Comment = L [[Zwitterion]]
}}
| Section2       = {{Chembox Properties
| Properties_ref = <ref>{{RubberBible62nd|page=C-374}}.</ref>
| C=5 | H=11 | N=1 | O=2 | S=1
| Appearance = White crystalline powder
| Density = 1.340 g/cm<sup>3</sup>
| MeltingPtC = 281
| MeltingPt_notes = decomposes
| Solubility = Soluble
| pKa =2.28 (carboxyl), 9.21 (amino)<ref>{{Cite book |last1=Dawson |first1=Rex M. C. |title=Data for Biochemical Research |last2=Elliott |first2=Daphne C. |last3=Elliott |first3=William H. |last4=Jones |first4=K. M. |date=1959 |publisher=Clarendon Press |location=Oxford |name-list-style=vanc}}</ref>
  }}
| Section6       = {{Chembox Pharmacology
| ATCCode_prefix = V03
| ATCCode_suffix = AB26
| ATC_Supplemental = {{ATCvet|A05|BA90}}, {{ATCvet|G04|BA90}}
}}
| Section7       = {{Chembox Hazards
| FlashPt =
 }}
}}
[[File:Methionine-spin.gif|thumb|Methionine ball and stick model spinning]]
'''Methionine''' (symbol '''Met''' or '''M''')<ref>{{Cite web |url=http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html |title=Nomenclature and Symbolism for Amino Acids and Peptides |year=1983 |publisher=IUPAC-IUB Joint Commission on Biochemical Nomenclature |url-status=dead |archive-url=https://web.archive.org/web/20081009023202/http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html |archive-date=9 October 2008 |access-date=5 March 2018}}</ref> ({{IPAc-en|m|ɪ|ˈ|θ|aɪ|ə|n|iː|n}})<ref>{{Cite web |url=https://en.oxforddictionaries.com/definition/methionine |archive-url=https://web.archive.org/web/20180127083819/https://en.oxforddictionaries.com/definition/methionine |url-status=dead |archive-date=January 27, 2018 |title=Methionine |publisher=Oxford University Press}}</ref> is an [[essential amino acid]] in humans.

As the precursor of other non-essential 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. Methionine is also involved in [[angiogenesis]] and various processes related to DNA transcription, epigenetic expression, and gene regulation.

Methionine was first isolated in 1921 by [[John Howard Mueller]].<ref>{{Cite web |url=http://www.nasonline.org/publications/biographical-memoirs/memoir-pdfs/mueller-john.pdf |title=A Biographical Memoir of John Howard Mueller |date=1987 |publisher=National Academy of Sciences |location=Washington D.C. |vauthors=Pappenheimer AM}}</ref> It is [[Genetic code|encoded]] by the [[codon]] AUG. It was named by Satoru Odake in 1925, as an abbreviation of its structural description 2-amino-4-('''meth'''ylt'''hio''')butanoic acid.<ref>{{Cite journal |last=Odake |first=Satoru |date=1925 |title=On the Occurrence of a Sulphur-containing Amino acid in Yeast |url=http://dx.doi.org/10.1271/bbb1924.1.87 |journal=Bulletin of the Agricultural Chemical Society of Japan |volume=1 |issue=8 |pages=87–89 |doi=10.1271/bbb1924.1.87 |issn=1881-1272}}</ref>

==Biochemical details==
Methionine (abbreviated as '''Met''' or '''M'''; encoded by the codon AUG) is an α-[[amino acid]] that is used in the [[biosynthesis]] of [[protein]]s. It contains a [[carboxyl group]] (which is in the deprotonated −COO<sup>−</sup> form under biological [[pH]] conditions), an [[amino group]] (which is in the [[protonated]] {{chem|−NH|3|+}} 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 [[Chemical polarity|nonpolar]], [[Aliphatic compound|aliphatic]] amino acid.{{cn|date=October 2024}}

In nuclear genes of [[eukaryote]]s 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 [[Peptide|polypeptide]] during [[mRNA]] [[Translation (biology)|translation]].<ref>{{Cite journal |vauthors=Guedes RL, Prosdocimi F, Fernandes GR, Moura LK, Ribeiro HA, Ortega JM |date=December 2011 |title=Amino acids biosynthesis and nitrogen assimilation pathways: a great genomic deletion during eukaryotes evolution |journal=BMC Genomics |volume=12 |issue=Suppl 4 |pages=S2 |doi=10.1186/1471-2164-12-S4-S2 |pmc=3287585 |pmid=22369087 |doi-access=free }}</ref>

==A proteinogenic amino acid==
[[Cysteine]] and methionine are the two [[sulfur]]-containing [[proteinogenic amino acid]]s. Excluding the few exceptions where methionine may act as a [[redox sensor]] (e.g.,[[methionine sulfoxide]]<ref>{{Cite journal |vauthors=Bigelow DJ, Squier TC |date=January 2005 |title=Redox modulation of cellular signaling and metabolism through reversible oxidation of methionine sensors in calcium regulatory proteins |journal=Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics |url=https://zenodo.org/record/1258778 |type=Submitted manuscript |volume=1703 |issue=2 |pages=121–134 |doi=10.1016/j.bbapap.2004.09.012 |pmid=15680220}}</ref>), methionine residues do not have a catalytic role.<ref name="review">{{Cite journal |vauthors=Ferla MP, Patrick WM |date=August 2014 |title=Bacterial methionine biosynthesis |journal=Microbiology |volume=160 |issue=Pt 8 |pages=1571–1584 |doi=10.1099/mic.0.077826-0 |pmid=24939187|doi-access=free }}</ref> This is in contrast to cysteine residues, where the thiol group has a catalytic role in many proteins.<ref name=review/> The thioether within methionine does however have a minor structural role due to the stability effect of [[S/π interaction]]s between the side chain sulfur atom and aromatic amino acids in one-third of all known protein structures.<ref name=review/> 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.<ref>{{Cite journal |vauthors=Cirino PC, Tang Y, Takahashi K, Tirrell DA, Arnold FH |date=September 2003 |title=Global incorporation of norleucine in place of methionine in cytochrome P450 BM-3 heme domain increases peroxygenase activity |journal=Biotechnology and Bioengineering |volume=83 |issue=6 |pages=729–734 |doi=10.1002/bit.10718 |pmid=12889037|s2cid=11380413 }}</ref>
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|''S''-adenosylmethionine]] (SAM-e).<ref>{{Cite journal |vauthors=Alvarez-Carreño C, Becerra A, Lazcano A |date=October 2013 |title=Norvaline and norleucine may have been more abundant protein components during early stages of cell evolution |journal=Origins of Life and Evolution of the Biosphere |volume=43 |issue=4–5 |pages=363–375 |bibcode=2013OLEB...43..363A |doi=10.1007/s11084-013-9344-3 |pmid=24013929|s2cid=17224537 }}</ref> This situation is not unique and may have occurred with [[ornithine]] and [[arginine]].<ref>{{Cite journal |vauthors=Jukes TH |date=August 1973 |title=Arginine as an evolutionary intruder into protein synthesis |journal=Biochemical and Biophysical Research Communications |volume=53 |issue=3 |pages=709–714 |doi=10.1016/0006-291x(73)90151-4 |pmid=4731949}}</ref>

===Encoding===
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 [[Vertebrate mitochondrial code|metazoa]] and [[The yeast mitochondrial code|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 (nucleoside)|lysidine]] (bacteria) or [[agmatidine]] (archaea) to discriminate against AUG.<ref>{{Cite journal |vauthors=Ikeuchi Y, Kimura S, Numata T, Nakamura D, Yokogawa T, Ogata T, Wada T, Suzuki T, Suzuki T |date=April 2010 |title=Agmatine-conjugated cytidine in a tRNA anticodon is essential for AUA decoding in archaea |journal=Nature Chemical Biology |volume=6 |issue=4 |pages=277–282 |doi=10.1038/nchembio.323 |pmid=20139989}}</ref><ref>{{Cite journal |vauthors=Muramatsu T, Nishikawa K, Nemoto F, Kuchino Y, Nishimura S, Miyazawa T, Yokoyama S |date=November 1988 |title=Codon and amino-acid specificities of a transfer RNA are both converted by a single post-transcriptional modification |journal=Nature |volume=336 |issue=6195 |pages=179–181 |bibcode=1988Natur.336..179M |doi=10.1038/336179a0 |pmid=3054566|s2cid=4371485 }}</ref>

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 (biology)|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 [[protein]]s in [[eukaryote]]s and [[archaea]] during translation, although it can be removed by [[post-translational modification]]. In [[bacteria]], the derivative [[N-Formylmethionine|''N''-formylmethionine]] is used as the initial amino acid.{{cn|date=October 2024}}

==Derivatives==

===''S''-Adenosylmethionine===
[[File:S-Adenosyl-L-methionin.svg|thumbnail|left|''S''-Adenosylmethionine is a cofactor derived from methionine.]]
{{Main|S-Adenosylmethionine}}
The methionine-derivative [[S-adenosyl methionine|''S''-adenosylmethionine]] (SAM-e) is a [[cofactor (biochemistry)|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 [[HSAB theory|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 B<sub>12</sub> in humans). Some enzymes use SAM-e to initiate a radical reaction; these are called [[radical SAM|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]], which is excreted as a waste product or quorum signal.{{cn|date=October 2024}}

== Biosynthesis ==
[[File:Met biosynthesis.svg|thumb|550px|Methionine biosynthesis]]
As an essential amino acid, methionine is not synthesized [[De novo synthesis|''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 [[Alpha-Aminoadipic acid|α-aminoadipate]]). The main backbone is derived from [[aspartic acid]], while the sulfur may come from [[cysteine]], [[methanethiol]], or [[hydrogen sulfide]].<ref name=review/>
* First, aspartic acid is converted via β-aspartyl semialdehyde into [[homoserine]] by two reduction steps of the terminal carboxyl group (homoserine has therefore a γ-hydroxyl, hence the [[homologous series|homo-]] series). The intermediate aspartate semialdehyde is the branching point with the lysine biosynthetic pathway, where it is instead [[Aldol condensation|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).<ref name=review/>
* Homoserine is then activated with a phosphate, succinyl or an acetyl group on the hydroxyl.
** In plants and possibly in some bacteria,<ref name=review/> phosphate is used. This step is shared with threonine biosynthesis.<ref name=review/>
** 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).<ref name=review/>
** In [[Enterobacteriaceae|enterobacteria]] 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.<ref name=review/> 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 reaction|elimination]] followed by a variant of a [[Michael addition]]. All the enzymes involved are homologues and members of the [[Cys/Met metabolism PLP-dependent enzyme family]], which is a subset of the PLP-dependent fold type I clade. They utilise the cofactor PLP ([[pyridoxal phosphate]]), which functions by stabilising carbanion intermediates.<ref name=review/>
** If it reacts with cysteine, it produces [[cystathionine]], which is cleaved to yield [[homocysteine]]. The enzymes involved are [[cystathionine-γ-synthase]] (encoded by ''metB'' in bacteria) and [[cystathionine-β-lyase]] (''metC''). Cystathionine is bound differently in the two enzymes allowing β or γ reactions to occur.<ref name=review/>
** If it reacts with free hydrogen sulfide, it produces homocysteine. This is catalysed by [[O-acetylhomoserine aminocarboxypropyltransferase|''O''-acetylhomoserine aminocarboxypropyltransferase]] (formerly known as ''O''-acetylhomoserine (thiol)-lyase. It is encoded by either ''metY'' or ''metZ'' in bacteria.<ref name=review/>
** 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.<ref name=review/>
* If homocysteine is produced, the thiol group is methylated, yielding methionine. Two [[methionine synthase]]s are known; one is [[cobalamin]] (vitamin B<sub>12</sub>) dependent and one is independent.<ref name=review/>

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 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.<ref>{{Cite journal |vauthors=Mino K, Ishikawa K |date=September 2003 |title=A novel ''O''-phospho-<small>L</small>-serine sulfhydrylation reaction catalyzed by ''O''-acetylserine sulfhydrylase from ''Aeropyrum pernix'' K1 |journal=FEBS Letters |volume=551 |issue=1–3 |pages=133–138 |doi=10.1016/S0014-5793(03)00913-X |pmid=12965218|s2cid=28360765 |doi-access=free }}</ref> CysK and CysM are homologues, but belong to the PLP fold type III clade.{{cn|date=October 2024}}

===Transsulfurylation pathway===
{{Main|Transsulfuration pathway}}
Enzymes involved in the ''E. coli'' transsulfurylation route of methionine biosynthesis:{{cn|date=October 2024}}
# [[Aspartokinase]]
# [[Aspartate-semialdehyde dehydrogenase]]
# [[Homoserine dehydrogenase]]
# [[Homoserine O-transsuccinylase|Homoserine ''O''-transsuccinylase]]
# [[Cystathionine-γ-synthase]]
# [[Cystathionine-β-lyase]]
# [[Methionine synthase]] (in mammals, this step is performed by [[homocysteine methyltransferase]] or [[betaine—homocysteine S-methyltransferase|betaine—homocysteine ''S''-methyltransferase]].)

== Other biochemical pathways ==
[[File:Met pathway.svg|thumb|400px|Fates of methionine]]
Although mammals cannot synthesize methionine, they can still use it in a variety of biochemical pathways:

===Catabolism===
Methionine is converted to [[S-adenosylmethionine|''S''-adenosylmethionine]] (SAM-e) by (1) [[methionine adenosyltransferase]].{{cn|date=October 2024}}

SAM-e serves as a methyl donor in many (2) [[methyltransferase]] reactions, and is converted to [[S-adenosylhomocysteine|''S''-adenosylhomocysteine]] (SAH).{{cn|date=October 2024}}

(3) [[Adenosylhomocysteinase]]
cysteine.

===Regeneration===
Methionine can be regenerated from homocysteine via (4) [[methionine synthase]] in a reaction that requires [[Vitamin B12|vitamin B<sub>12</sub>]] as a [[cofactor (biochemistry)|cofactor]].{{cn|date=October 2024}}

Homocysteine can also be remethylated using [[glycine betaine]] (''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.{{cn|date=October 2024}}

===Reverse-transulfurylation pathway: conversion to cysteine===
Homocysteine can be converted to cysteine.
* (5) [[Cystathionine-β-synthase]] (an enzyme which requires [[pyridoxal phosphate]], the active form of [[vitamin B6]]) 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]].{{cn|date=October 2024}}
* (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).{{cn|date=October 2024}}

===Ethylene synthesis===
This [[amino acid]] is also used by [[plant]]s for synthesis of [[ethylene]]. The process is known as the [[Shang Fa Yang|Yang]] cycle or the methionine cycle.
[[File:Yang-cycle.svg|thumb|none|The Yang cycle]]

== Metabolic diseases ==
The degradation of methionine is impaired in the following [[Metabolic disorder|metabolic diseases]]:{{cn|date=October 2024}}
* [[Combined malonic and methylmalonic aciduria]] (CMAMMA)
* [[Homocystinuria]]
* [[Methylmalonic acidemia]]
* [[Propionic acidemia]]

==Chemical synthesis==
The industrial synthesis combines [[acrolein]], [[methanethiol]], and cyanide, which affords the [[hydantoin]].<ref>{{Ullmann |author=Karlheinz Drauz |author2=Ian Grayson |author3=Axel Kleemann |author4=Hans-Peter Krimmer |author5=Wolfgang Leuchtenberger |author6=Christoph Weckbecker |year=2006|doi=10.1002/14356007.a02_057.pub2}}</ref> [[Racemic]] methionine can also 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. Also see Methanol. <ref>{{OrgSynth | last1 = Barger | first1 = G. | last2 = Weichselbaum | first2 = T. E. | name-list-style = vanc | title = ''dl''-Methionine | prep = CV2P0384 | volume = 14 | pages = 58 | year = 1934 | collvol = 2 | collvolpages = 384}}</ref>

==Human nutrition==

There is inconclusive clinical evidence on methionine supplementation.<ref name="Navik 2021">{{cite journal|author=Navik U, Sheth VG, Khurana A, Jawalekar SS, Allawadhi P, Gaddam RR, Bhatti JS, Tikoo K.|year=2021|title=Methionine as a double-edged sword in health and disease: Current perspective and future challenges|journal=Ageing Res Rev|volume=72|issue=|pages=101500|pmid=34700006|doi=10.1016/j.arr.2021.101500}}</ref> Dietary restriction of methionine can lead to bone-related disorders.<ref name="Navik 2021"/>

Methionine supplementation may benefit those suffering from [[Copper toxicity|copper poisoning]].<ref>{{Cite web |url=http://www.webmd.com/vitamins-supplements/ingredientmono-42-methionine.aspx?activeingredientid=42& |title=Methionine |website=WebMD}}</ref>

Overconsumption of methionine, the [[methyl group]] donor in [[DNA methylation]], is related to cancer growth in a number of studies.<ref name="Cavuoto_2012">{{Cite journal |vauthors=Cavuoto P, Fenech MF |year=2012 |title=A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension |journal=Cancer Treatment Reviews |volume=38 |issue=6 |pages=726–736 |doi=10.1016/j.ctrv.2012.01.004 |pmid=22342103}}</ref><ref name="Cellarier_2003">{{Cite journal |vauthors=Cellarier E, Durando X, Vasson MP, Farges MC, Demiden A, Maurizis JC, Madelmont JC, Chollet P |year=2003 |title=Methionine dependency and cancer treatment |journal=Cancer Treatment Reviews |volume=29 |issue=6 |pages=489–499 |doi=10.1016/S0305-7372(03)00118-X |pmid=14585259}}</ref>

===Requirements===
The Food and Nutrition Board <!-- (FNB) --> of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) for [[essential amino acid]]s in 2002. For methionine combined with cysteine, for adults 19 years and older, 19&nbsp;mg/kg body weight/day.<ref name="DRItext">{{Cite book |last=Institute of Medicine |title=Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids |publisher=The National Academies Press |year=2002 |location=Washington, DC |pages=589–768 |chapter=Protein and Amino Acids |doi=10.17226/10490 |isbn=978-0-309-08525-0 |author-link=Institute of Medicine |chapter-url=https://www.nap.edu/read/10490/chapter/12}}</ref>

This translates to about 1.33 grams per day for a 70 kilogram individual.{{cn|date=October 2024}}

===Dietary sources===
{|class="wikitable sortable" align=right
|+ Food sources of methionine{{citation needed|date=April 2022}}
|-
! Food
! g/100&nbsp;g
|-
| [[Egg (food)|Egg]], white, dried, powder, glucose reduced || 3.204
|-
| [[Sesame seed]]s flour (low fat) || 1.656
|-
| [[Brazil nut]]s || 1.124
|-
| [[Cheese]], Parmesan, shredded || 1.114
|-
| [[hemp seed]], hulled || 0.933
|-
| [[Soy protein#Concentrates|Soy protein concentrate]] || 0.814
|-
| [[Chicken (food)|Chicken]], broilers or fryers, roasted || 0.801
|-
| [[Fish (food)|Fish]], tuna, light, canned in water, drained solids || 0.755
|-
| [[Beef]], cured, dried || 0.749
|-
| [[Bacon]] || 0.593
|-
| [[chia seed]]s || 0.588
|-
| [[Beef]], ground, 95% lean meat / 5% fat, raw || 0.565
|-
| [[Pork]], ground, 96% lean / 4% fat, raw || 0.564
|-
|[[Soybean#Nutrition|Soybeans]]
|0.547
|-
| [[Wheat germ]] || 0.456
|-
| [[Egg]], whole, cooked, hard-boiled || 0.392
|-
| [[Oat]] || 0.312
|-
| [[Peanut]]s || 0.309
|-
| [[Chickpea]] || 0.253
|-
| [[Maize|Corn]], yellow || 0.197
|-
| [[Almond]]s || 0.151
|-
| Beans, pinto, cooked || 0.117
|-
| [[Lentil]]s, cooked || 0.077
|-
| [[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 [[legume]]s, though protein dense, are low in methionine. Proteins without adequate methionine are not considered to be [[complete protein]]s.<ref>{{Cite journal |vauthors=Finkelstein JD |date=May 1990 |title=Methionine metabolism in mammals |journal=The Journal of Nutritional Biochemistry |volume=1 |issue=5 |pages=228–237 |doi=10.1016/0955-2863(90)90070-2 |pmid=15539209|s2cid=32264340 }}</ref> For that reason, racemic methionine is sometimes added as an ingredient to [[pet food]]s.<ref>{{Cite book |last=Palika |first=Liz |title=The Consumer's Guide to Dog Food: What's in Dog Food, Why It's There and How to Choose the Best Food for Your Dog |date=1996 |publisher=Howell Book House |isbn=978-0-87605-467-3 |location=New York |name-list-style=vanc}}</ref>

==Health==
Loss of methionine has been linked to senile greying of hair. Its lack leads to a buildup of [[hydrogen peroxide]] in [[hair follicle]]s, a reduction in [[tyrosinase]] effectiveness, and a gradual loss of hair color.<ref>{{cite journal | vauthors = Wood JM, Decker H, Hartmann H, Chavan B, Rokos H, Spencer JD, Hasse S, Thornton MJ, Shalbaf M, Paus R, Schallreuter KU | title = Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair | journal = FASEB Journal | volume = 23 | issue = 7 | pages = 2065–75 | date = July 2009 | pmid = 19237503 | doi = 10.1096/fj.08-125435 | doi-access = free | display-authors = 6 | hdl = 10454/6241 | arxiv = 0706.4406 | s2cid = 16069417 }}</ref> 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.<ref>{{cite journal | vauthors = Pinnen F | display-authors = etal | year = 2009 | title = Codrugs linking <small>L</small>-dopa and sulfur-containing antioxidants: new pharmacological tools against Parkinson's disease | journal = Journal of Medicinal Chemistry | volume = 52 | issue = 2| pages = 559–63 | doi = 10.1021/jm801266x | pmid = 19093882 }}</ref>

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]]<ref>{{cite journal | vauthors = Refsum H, Ueland PM, Nygård O, Vollset SE | title = Homocysteine and cardiovascular disease | journal = Annual Review of Medicine | volume = 49 | issue = 1 | pages = 31–62 | date = 1998 | pmid = 9509248 | doi = 10.1146/annurev.med.49.1.31 }}</ref> due to accumulation of [[homocysteine]].

==Other uses==
<small>DL</small>-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.<ref>Grimshaw, Jane (July 25, 2011) [https://web.archive.org/web/20140629112302/http://www.critters360.com/index.php/methionine-for-dogs-uses-and-side-effects-3841/ Methionine for Dogs uses and Side Effects]. critters360.com</ref>

Methionine is allowed as a supplement to organic poultry feed under the US certified organic program.<ref>{{Cite journal | title =Rules and Regulations |journal=Federal Register | url = http://edocket.access.gpo.gov/2011/2011-5716.htm | volume= 76|issue= 49 |date=March 14, 2011|pages =13501–13504}}</ref>

Methionine can be used as a nontoxic pesticide option against [[Papilio cresphontes|giant swallowtail]] caterpillars, which are a serious pest to orange crops.<ref>{{cite journal | vauthors = Lewis DS, Cuda JP, Stevens BR | title = A novel biorational pesticide: efficacy of methionine against ''Heraclides (Papilio) cresphontes'', a surrogate of the invasive ''Princeps (Papilio) demoleus'' (Lepidoptera: Papilionidae) | journal = Journal of Economic Entomology | volume = 104 | issue = 6 | pages = 1986–1990 | date = December 2011 | pmid = 22299361 | doi = 10.1603/ec11132 | s2cid = 45255198 | doi-access = free }}</ref>

== See also ==
* [[Allantoin]]
* [[Formylmethionine]]
* [[Methionine oxidation]]
* [[Paracetamol poisoning#Treatment|Paracetamol poisoning]]
* [[Photo-reactive amino acid analog|Photoreactive methionine]]
* [[S-Methylcysteine|''S''-Methylcysteine]]

== References ==
{{Reflist|32em}}

== External links ==
* {{Cite journal | title = Methionine Content of Cereals and Legumes | first1 = M. N. | last1 = Rudra | first2 = L. M. | last2 = Chowdhury | name-list-style = vanc | journal = [[Nature (journal)|Nature]] | volume = 166 | date = 30 September 1950 | doi = 10.1038/166568a0 | pmid = 14780151 | issue = 568 | pages = 568 |bibcode = 1950Natur.166..568R | s2cid = 3026278 | doi-access = free }}

{{Amino acids}}
{{Antidotes}}
{{Amino acid metabolism intermediates}}
{{Authority control}}

[[Category:Alpha-Amino acids]]
[[Category:Proteinogenic amino acids]]
[[Category:Glucogenic amino acids]]
[[Category:Sulfur amino acids]]
[[Category:Thioethers]]
[[Category:Essential amino acids]]