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Revision as of 11:49, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{chembox}} taken from revid 477140944 of page Lysine for the Chem/Drugbox validation project (updated: 'KEGG', 'CASNo').  Latest revision as of 09:43, 30 December 2024 edit Norman21 (talk | contribs)Extended confirmed users1,442 editsm Reverted 2 edits by 2001:F90:6019:15D5:F85E:CBFF:FEF3:2D50 (talk) to last revision by DMacksTags: Twinkle Undo 
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{{Short description|Amino acid}}
{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}}
{{Distinguish|lysin|leucine}}
{{Use dmy dates|date=May 2018}}
{{chembox {{chembox
|ImageFile1 = L-Lysin - L-Lysine.svg
| Verifiedfields = changed
|ImageCaption1 = ] of <small>L</small>-lysine
| UNII_Ref = {{fdacite|correct|FDA}}
|ImageFileL2 = Lysine-from-xtal-3D-bs-17.png
| UNII = K3Z4F929H6
|ImageSizeL2 = 100px
| verifiedrevid = 458441640
|ImageCaptionL2 = ]<ref name="Williams">{{ cite journal | title = L-Lysine: Exploiting Powder X-ray Diffraction to Complete the Set of Crystal Structures of the 20 Directly Encoded Proteinogenic Amino Acids | first1 = P. A. | last1 = Williams | first2 = C. E. | last2 = Hughes | first3 = K. D. M | last3 = Harris | journal = ] | volume = 54 | issue = 13 | pages = 3973–3977 | year = 2015 | doi = 10.1002/anie.201411520 | pmid = 25651303 }}</ref>
| ImageFileL1_Ref = {{chemboximage|correct|??}}
| ImageFileL1 = L-lysine-2D-skeletal.png |ImageFileR2 = Lysine-from-xtal-3D-sf.png
| ImageSizeL1 = 120px |ImageSizeR2 = 120px
|ImageCaptionR2 = ]<ref name="Williams" />
| ImageNameL1 = Skeletal formula of the L-isomer (neutral form)
|SystematicName = (2''S'')-2,6-Diaminohexanoic acid (<small>L</small>-lysine)
| ImageFileR1 = L-lysine-monocation-from-hydrochloride-dihydrate-xtal-3D-balls.png
(2''R'')-2,6-Diaminohexanoic acid (<small>D</small>-lysine)
| ImageSizeR1 = 120px
|IUPACName = <small>L</small>-lysine
| ImageNameR1 = Ball-and-stick model of lysine at physiological pH (zwitterionic form)
<br><small>D</small>-lysine
| IUPACName = Lysine
|OtherNames = Lysine, <small>D</small>-lysine, <small>L</small>-lysine, LYS, h-Lys-OH
| OtherNames = 2,6-diaminohexanoic acid
| Section1 = {{Chembox Identifiers |Section1={{Chembox Identifiers
|UNII_Ref = {{fdacite|correct|FDA}}
| InChI = 1/C6H14N2O2/c7-4-2-1-3-5(8)6(9)10/h5H,1-4,7-8H2,(H,9,10)
|UNII = AI4RT59273
| InChIKey = KDXKERNSBIXSRK-UHFFFAOYAY
|UNII_Comment = <small>DL</small>
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|UNII1_Ref = {{fdacite|correct|FDA}}
| StdInChI = 1S/C6H14N2O2/c7-4-2-1-3-5(8)6(9)10/h5H,1-4,7-8H2,(H,9,10)
|UNII1 = K3Z4F929H6
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|UNII1_Comment = <small>L</small>
| StdInChIKey = KDXKERNSBIXSRK-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|changed|??}} |UNII2_Ref = {{fdacite|correct|FDA}}
|UNII2 = 3HQ6U6424Q
| CASNo = <!-- blanked - oldvalue: 70-54-2 -->
| CASNo_Comment = <small>DL</small> |UNII2_Comment = <small>D</small>
|InChI = 1/C6H14N2O2/c7-4-2-1-3-5(8)6(9)10/h5H,1-4,7-8H2,(H,9,10)
| CASNo1_Comment = <small>L</small>
|InChIKey = KDXKERNSBIXSRK-UHFFFAOYAY
| CASNo1 = 56-87-1
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| CASNo2_Comment = <small>D</small>
|StdInChI = 1S/C6H14N2O2/c7-4-2-1-3-5(8)6(9)10/h5H,1-4,7-8H2,(H,9,10)
| CASNo2 = 923-27-3
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = KDXKERNSBIXSRK-UHFFFAOYSA-N
| ChemSpiderID = 843
|CASNo_Ref = {{cascite|correct|CAS}}
| ChemSpiderID1 = 5747
|CASNo= 70-54-2
| ChemSpiderID1_Comment = <small>L</small>
|CASNo_Comment = <small>DL</small>
| PubChem = 866
|CASNo1_Comment = <small>L</small>
| ChEMBL_Ref = {{ebicite|correct|EBI}}
|CASNo1_Ref = {{cascite|correct|CAS}}
| ChEMBL = 28328
|CASNo1 = 56-87-1
| KEGG_Ref = {{keggcite|changed|kegg}}
|CASNo2_Comment = <small>D</small>
| KEGG = C00047
|CASNo2_Ref = {{cascite|correct|??}}
| IUPHAR_ligand = 724
|CASNo2 = 923-27-3
| ChEBI_Ref = {{ebicite|correct|EBI}}
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChEBI = 25094
|ChemSpiderID = 843
| SMILES = C(CCN)CC(C(=O)O)N
|ChemSpiderID1_Ref = {{chemspidercite|correct|chemspider}}
| ATCCode_prefix = B05
|ChemSpiderID1 = 5747
| ATCCode_suffix = XB03
|ChemSpiderID1_Comment = <small>L</small>
|PubChem = 866
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 28328
|KEGG_Ref = {{keggcite|correct|kegg}}
|KEGG = C16440
|IUPHAR_ligand = 724
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI = 25094
|SMILES = C(CCN)C(C(=O)O)N
|SMILES1 = C(CC)C(C(=O))N
|SMILES1_Comment = ]
|SMILES2 = C(CC)C(C(=O))
|SMILES2_Comment = Protonated zwitterion
}} }}
| Section2 = {{Chembox Properties |Section2={{Chembox Properties
| C=6 | H=14 | N=2 | O=2 |C=6 | H=14 | N=2 | O=2
|Solubility = 1.5&nbsp;kg/L
| Appearance =
| Density =
| MeltingPt =
| BoilingPt =
| Solubility = 1.5kg/L @ 25 °C<ref>http://www.peptideguide.com/amino-acids/lysine.html</ref> }}
| Section3 = {{Chembox Hazards
| MainHazards =
| FlashPt =
| Autoignition = }}
}} }}
|Section3={{Chembox Pharmacology
|ATCCode_prefix = B05
|ATCCode_suffix = XB03
}}
}}

'''Lysine''' (symbol '''Lys''' or '''K''')<ref>{{cite journal |title=IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature and symbolism for amino acids and peptides. Recommendations 1983 |journal=Biochemical Journal |date=15 April 1984 |volume=219 |issue=2 |pages=345–373 |pmc=1153490 |doi=10.1042/bj2190345|pmid=6743224 }}</ref> is an ] that is a ] to many ]. Lysine contains an α-amino group (which is in the ] {{chem2|\sNH3+}} form when the lysine is dissolved in water at ]), an α-carboxylic acid group (which is in the deprotonated {{chem2|\sCOO-}} form when the lysine is dissolved in water at physiological pH), and a side chain {{chem2|(CH2)4NH2}} (which is partially protonated when the lysine is dissolved in water at physiological pH), and so it is classified as a ], charged (in water at physiological pH), ] amino acid. It is encoded by the ]s AAA and AAG. Like almost all other amino acids, the α-carbon is ] and lysine may refer to either ] or a ] of both. For the purpose of this article, lysine will refer to the biologically active enantiomer <small>L</small>-lysine, where the α-carbon is in the ''S'' configuration.

The human body cannot synthesize lysine. It is ] and must therefore be obtained from the diet. In organisms that synthesise lysine, two main ] exist, the ] and ] pathways, which employ distinct ] and ] and are found in diverse organisms. Lysine ] occurs through one of several pathways, the most common of which is the ].

Lysine plays several roles in humans, most importantly ], but also in the crosslinking of ] polypeptides, uptake of essential mineral nutrients, and in the production of ], which is key in ]. Lysine is also often involved in ]s, and thus, impacts the ]. The ε-amino group often participates in hydrogen bonding and as a general base in ]. The ε-] group ({{chem2|\sNH3+}}) is attached to the fourth carbon from the α-carbon, which is attached to the ] ({{chem2|\sCOOH}}) group.<ref> The Biology Project, Department of Biochemistry and Molecular Biophysics, University of Arizona.</ref>

Due to its importance in several biological processes, a lack of lysine can lead to several disease states including defective connective tissues, impaired fatty acid metabolism, anaemia, and systemic protein-energy deficiency. In contrast, an overabundance of lysine, caused by ineffective catabolism, can cause severe ]s.

Lysine was first isolated by the German biological chemist Ferdinand Heinrich Edmund Drechsel in 1889 from hydrolysis of the protein ],<ref>{{cite journal | vauthors = Drechsel E | title=Zur Kenntniss der Spaltungsprodukte des Caseïns|journal=Journal für Praktische Chemie|date=1889|volume=39|pages=425–429|url=https://babel.hathitrust.org/cgi/pt?id=osu.32435060196680;view=1up;seq=441|series=2nd series|trans-title= to knowledge of the cleavage products of casein|language=de| doi=10.1002/prac.18890390135}} On p. 428, Drechsel presented an empirical formula for the chloroplatinate salt of lysine – C<sub>8</sub>H<sub>16</sub>N<sub>2</sub>O<sub>2</sub>Cl<sub>2</sub>·PtCl<sub>4</sub> + H<sub>2</sub>O – but he later admitted that this formula was wrong because the salt's crystals contained ethanol instead of water. See: {{cite journal | vauthors = Drechsel E | year = 1891 | title = Der Abbau der Eiweissstoffe | trans-title = The disassembly of proteins | language = de | journal = Archiv für Anatomie und Physiologie | pages = 248–278 |postscript=;}} {{cite web | vauthors = Drechsel E | title = Zur Kenntniss der Spaltungsproducte des Caseïns | year = 1877 | trans-title = Contribution] to knowledge of the cleavage products of casein | language = de | pages = 254–260 | url = https://babel.hathitrust.org/cgi/pt?id=coo.31924056294253;view=1up;seq=268 | quote = From p. 256:] ''" … die darin enthaltene Base hat die Formel C<sub>6</sub>H<sub>14</sub>N<sub>2</sub>O<sub>2</sub>. Der anfängliche Irrthum ist dadurch veranlasst worden, dass das Chloroplatinat nicht, wie angenommen ward, Krystallwasser, sondern Krystallalkohol enthält, … "'' ( … the base contained therein has the formula C<sub>6</sub>H<sub>14</sub>N<sub>2</sub>O<sub>2</sub>. The initial error was caused by the chloroplatinate containing not water in the crystal (as was assumed), but ethanol … ) }}</ref> and thus named it Lysin, {{ety|el|''λύσις'' (lysis)|loosening}}.<ref>{{Cite journal |last1=Vickery |first1=Hubert Bradford. |last2=Schmidt |first2=Carl L. A. |date=1931-10-01 |title=The History of the Discovery of the Amino Acids. |url=https://pubs.acs.org/doi/abs/10.1021/cr60033a001 |journal=Chemical Reviews |language=en |volume=9 |issue=2 |pages=169–318 |doi=10.1021/cr60033a001 |issn=0009-2665}}</ref><ref>{{cite journal | vauthors = Drechsel E | year = 1891 | title = Der Abbau der Eiweissstoffe | trans-title = The disassembly of proteins | language = de | journal = Archiv für Anatomie und Physiologie | pages = 248–278 }}; {{cite journal | last = Fischer | first = Ernst | name-list-style = vanc | year = 1891 | title = Ueber neue Spaltungsproducte des Leimes | trans-title = On new cleavage products of gelatin |journal=Archiv für Anatomie und Physiologie | language = de | pages = 465–469 | url = https://babel.hathitrust.org/cgi/pt?id=coo.31924056294253;view=1up;seq=281 | quote = From p. 469:] ''" … die Base C<sub>6</sub>H<sub>14</sub>N<sub>2</sub>O<sub>2</sub>, welche mit dem Namen Lysin bezeichnet werden mag, … "'' ( … the base C<sub>6</sub>H<sub>14</sub>N<sub>2</sub>O<sub>2</sub>, which may be designated with the name "lysine", … ) }}</ref> In 1902, the German chemists ] and ] determined lysine's chemical structure by synthesizing it.<ref>{{cite journal|last1=Fischer|first1=Emil|last2=Weigert|first2=Fritz | name-list-style = vanc |title=Synthese der α,ε – Diaminocapronsäure (Inactives Lysin)|journal=Berichte der Deutschen Chemischen Gesellschaft|date=1902|volume=35|issue=3|pages=3772–3778|url=https://babel.hathitrust.org/cgi/pt?id=hvd.cl1i27;view=1up;seq=1240|trans-title=Synthesis of α,ε-diaminohexanoic acid ( inactive lysine)|language=de|doi=10.1002/cber.190203503211}}</ref>

The one-letter symbol K was assigned to lysine for being alphabetically nearest, with L being assigned to the structurally simpler leucine, and M to methionine.<ref name=":1">{{Cite journal |last=Saffran |first=M. |date=April 1998 |title=Amino acid names and parlor games: from trivial names to a one-letter code, amino acid names have strained students' memories. Is a more rational nomenclature possible? |url=http://linkinghub.elsevier.com/retrieve/pii/S0307441297001672 |journal=Biochemical Education |language=en |volume=26 |issue=2 |pages=116–118 |doi=10.1016/S0307-4412(97)00167-2}}</ref>

==Biosynthesis==
]

Two pathways have been identified in nature for the synthesis of lysine. The ] (DAP) pathway belongs to the ] derived biosynthetic family, which is also involved in the synthesis of ], ] and ],<ref name="Hudson_2005">{{cite journal | vauthors = Hudson AO, Bless C, Macedo P, Chatterjee SP, Singh BK, Gilvarg C, Leustek T | title = Biosynthesis of lysine in plants: evidence for a variant of the known bacterial pathways | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1721 | issue = 1–3 | pages = 27–36 | date = January 2005 | pmid = 15652176 | doi = 10.1016/j.bbagen.2004.09.008 }}</ref><ref name="Velasco_2002">{{cite journal | vauthors = Velasco AM, Leguina JI, Lazcano A | title = Molecular evolution of the lysine biosynthetic pathways | journal = Journal of Molecular Evolution | volume = 55 | issue = 4 | pages = 445–459 | date = October 2002 | pmid = 12355264 | doi = 10.1007/s00239-002-2340-2 | bibcode = 2002JMolE..55..445V | s2cid = 19460256 }}</ref> whereas the ] (AAA) pathway is part of the ] biosynthetic family.<ref name="Miyazaki_2004">{{cite journal | vauthors = Miyazaki T, Miyazaki J, Yamane H, Nishiyama M | title = alpha-Aminoadipate aminotransferase from an extremely thermophilic bacterium, Thermus thermophilus | journal = Microbiology | volume = 150 | issue = Pt 7 | pages = 2327–2334 | date = July 2004 | pmid = 15256574 | doi = 10.1099/mic.0.27037-0 | doi-access = free | s2cid = 25416966 }}</ref><ref name="Xu_2006">{{cite journal | vauthors = Xu H, Andi B, Qian J, West AH, Cook PF | title = The alpha-aminoadipate pathway for lysine biosynthesis in fungi | journal = ] | volume = 46 | issue = 1 | pages = 43–64 | date = 2006 | pmid = 16943623 | doi = 10.1385/CBB:46:1:43 | s2cid = 22370361 }}</ref>

=== DAP pathway ===
The DAP pathway is found in both ]s and plants and begins with the ] (DHDPS) (E.C 4.3.3.7) ] ] between the aspartate derived, <small>L</small>-aspartate semialdehyde, and ] to form (4''S'')-4-hydroxy-2,3,4,5-tetrahydro-(2''S'')-dipicolinic acid (HTPA).<ref name="Atkinson_2013">{{cite journal | vauthors = Atkinson SC, Dogovski C, Downton MT, Czabotar PE, Dobson RC, Gerrard JA, Wagner J, Perugini MA | title = Structural, kinetic and computational investigation of Vitis vinifera DHDPS reveals new insight into the mechanism of lysine-mediated allosteric inhibition | journal = Plant Molecular Biology | volume = 81 | issue = 4–5 | pages = 431–446 | date = March 2013 | pmid = 23354837 | doi = 10.1007/s11103-013-0014-7 | hdl = 11343/282680 | s2cid = 17129774 | hdl-access = free }}</ref><ref name="Griffin_2012">{{cite journal | vauthors = Griffin MD, Billakanti JM, Wason A, Keller S, Mertens HD, Atkinson SC, Dobson RC, Perugini MA, Gerrard JA, Pearce FG | title = Characterisation of the first enzymes committed to lysine biosynthesis in Arabidopsis thaliana | journal = PLOS ONE | volume = 7 | issue = 7 | pages = e40318 | date = 2012 | pmid = 22792278 | pmc = 3390394 | doi = 10.1371/journal.pone.0040318 | bibcode = 2012PLoSO...740318G | doi-access = free }}</ref><ref name="Soares_da_Costa_2010">{{cite journal | vauthors = Soares da Costa TP, Muscroft-Taylor AC, Dobson RC, Devenish SR, Jameson GB, Gerrard JA | title = How essential is the 'essential' active-site lysine in dihydrodipicolinate synthase? | journal = Biochimie | volume = 92 | issue = 7 | pages = 837–845 | date = July 2010 | pmid = 20353808 | doi = 10.1016/j.biochi.2010.03.004 }}</ref><ref name="Soares_da_Costa_2015">{{cite book | vauthors = Soares da Costa TP, Christensen JB, Desbois S, Gordon SE, Gupta R, Hogan CJ, Nelson TG, Downton MT, Gardhi CK, Abbott BM, Wagner J, Panjikar S, Perugini MA | chapter = Quaternary Structure Analyses of an Essential Oligomeric Enzyme | volume = 562 | pages = 205–223 | date = 2015 | pmid = 26412653 | doi = 10.1016/bs.mie.2015.06.020 | series = Methods in Enzymology | isbn = 9780128029084 | title = Analytical Ultracentrifugation }}</ref><ref>{{cite journal | vauthors = Muscroft-Taylor AC, Soares da Costa TP, Gerrard JA | title = New insights into the mechanism of dihydrodipicolinate synthase using isothermal titration calorimetry | journal = Biochimie | volume = 92 | issue = 3 | pages = 254–262 | date = March 2010 | pmid = 20025926 | doi = 10.1016/j.biochi.2009.12.004 }}</ref> The product is then ] by ] (E.C 1.3.1.26), with ] as a proton donor, to yield 2,3,4,5-tetrahydrodipicolinate (THDP).<ref>{{cite journal | vauthors = Christensen JB, Soares da Costa TP, Faou P, Pearce FG, Panjikar S, Perugini MA | title = Structure and Function of Cyanobacterial DHDPS and DHDPR | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 37111 | date = November 2016 | pmid = 27845445 | pmc = 5109050 | doi = 10.1038/srep37111 | bibcode = 2016NatSR...637111C }}</ref> From this point on, four pathway variations have been found, namely the acetylase, aminotransferase, dehydrogenase, and succinylase pathways.<ref name="Hudson_2005" /><ref>{{cite journal | vauthors = McCoy AJ, Adams NE, Hudson AO, Gilvarg C, Leustek T, Maurelli AT | title = <small>L</small>,<small>L</small>-diaminopimelate aminotransferase, a trans-kingdom enzyme shared by Chlamydia and plants for synthesis of diaminopimelate/lysine | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 47 | pages = 17909–17914 | date = November 2006 | pmid = 17093042 | pmc = 1693846 | doi = 10.1073/pnas.0608643103 | bibcode = 2006PNAS..10317909M | doi-access = free }}</ref> Both the acetylase and succinylase variant pathways use four ] catalysed steps, the aminotransferase pathway uses two enzymes, and the dehydrogenase pathway uses a single enzyme.<ref>{{cite journal | vauthors = Hudson AO, Gilvarg C, Leustek T | title = Biochemical and phylogenetic characterization of a novel diaminopimelate biosynthesis pathway in prokaryotes identifies a diverged form of <small>LL</small>-diaminopimelate aminotransferase | journal = Journal of Bacteriology | volume = 190 | issue = 9 | pages = 3256–3263 | date = May 2008 | pmid = 18310350 | pmc = 2347407 | doi = 10.1128/jb.01381-07 }}</ref> These four variant pathways converge at the formation of the penultimate product, ''meso''‑diaminopimelate, which is subsequently enzymatically ] in an irreversible reaction catalysed by ] (E.C 4.1.1.20) to produce <small>L</small>-lysine.<ref>{{cite journal | vauthors = Peverelli MG, Perugini MA | title = An optimized coupled assay for quantifying diaminopimelate decarboxylase activity | journal = Biochimie | volume = 115 | pages = 78–85 | date = August 2015 | pmid = 25986217 | doi = 10.1016/j.biochi.2015.05.004 }}</ref><ref name="Soares_da_Costa_2016">{{cite journal | vauthors = Soares da Costa TP, Desbois S, Dogovski C, Gorman MA, Ketaren NE, Paxman JJ, Siddiqui T, Zammit LM, Abbott BM, Robins-Browne RM, Parker MW, Jameson GB, Hall NE, Panjikar S, Perugini MA | title = Structural Determinants Defining the Allosteric Inhibition of an Essential Antibiotic Target | journal = Structure | volume = 24 | issue = 8 | pages = 1282–1291 | date = August 2016 | pmid = 27427481 | doi = 10.1016/j.str.2016.05.019 | doi-access = free }}</ref> The DAP pathway is regulated at multiple levels, including upstream at the enzymes involved in aspartate processing as well as at the initial DHDPS catalysed condensation step.<ref name="Soares_da_Costa_2016" /><ref name="Jander_2009">{{cite journal | vauthors = Jander G, Joshi V | title = Aspartate-Derived Amino Acid Biosynthesis in Arabidopsis thaliana | journal = The Arabidopsis Book | volume = 7 | pages = e0121 | date = 2009-01-01 | pmid = 22303247 | pmc = 3243338 | doi = 10.1199/tab.0121 }}</ref> Lysine imparts a strong ] loop on these enzymes and, subsequently, regulates the entire pathway.<ref name="Jander_2009" />

=== AAA pathway ===
{{Main|α-Aminoadipate pathway}}
The AAA pathway involves the condensation of ] and ] via the intermediate AAA for the synthesis of <small>L</small>-lysine. This pathway has been shown to be present in several ] species, as well as protists and higher fungi.<ref name="Xu_2006" /><ref>{{cite journal | vauthors = Andi B, West AH, Cook PF | title = Kinetic mechanism of histidine-tagged homocitrate synthase from Saccharomyces cerevisiae | journal = Biochemistry | volume = 43 | issue = 37 | pages = 11790–11795 | date = September 2004 | pmid = 15362863 | doi = 10.1021/bi048766p }}</ref><ref>{{cite journal | vauthors = Bhattacharjee JK | title = alpha-Aminoadipate pathway for the biosynthesis of lysine in lower eukaryotes | journal = Critical Reviews in Microbiology | volume = 12 | issue = 2 | pages = 131–151 | date = 1985 | pmid = 3928261 | doi = 10.3109/10408418509104427 }}</ref><ref>{{cite journal | vauthors = Bhattacharjee JK, Strassman M | title = Accumulation of tricarboxylic acids related to lysine biosynthesis in a yeast mutant | journal = The Journal of Biological Chemistry | volume = 242 | issue = 10 | pages = 2542–2546 | date = May 1967 | doi = 10.1016/S0021-9258(18)95997-1 | pmid = 6026248 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Gaillardin CM, Ribet AM, Heslot H | title = Wild-type and mutant forms of homoisocitric dehydrogenase in the yeast Saccharomycopsis lipolytica | journal = European Journal of Biochemistry | volume = 128 | issue = 2–3 | pages = 489–494 | date = November 1982 | pmid = 6759120 | doi = 10.1111/j.1432-1033.1982.tb06991.x | doi-access = free}}</ref><ref>{{cite journal | vauthors = Jaklitsch WM, Kubicek CP | title = Homocitrate synthase from Penicillium chrysogenum. Localization, purification of the cytosolic isoenzyme, and sensitivity to lysine | journal = The Biochemical Journal | volume = 269 | issue = 1 | pages = 247–253 | date = July 1990 | pmid = 2115771 | pmc = 1131560 | doi = 10.1042/bj2690247 }}</ref><ref>{{cite journal | vauthors = Ye ZH, Bhattacharjee JK | title = Lysine biosynthesis pathway and biochemical blocks of lysine auxotrophs of Schizosaccharomyces pombe | journal = Journal of Bacteriology | volume = 170 | issue = 12 | pages = 5968–5970 | date = December 1988 | pmid = 3142867 | pmc = 211717 | doi = 10.1128/jb.170.12.5968-5970.1988 }}</ref> It has also been reported that an alternative variant of the AAA route has been found in '']'' and '']'', which could indicate that this pathway is more widely spread in prokaryotes than originally proposed.<ref>{{cite journal | vauthors = Kobashi N, Nishiyama M, Tanokura M | title = Aspartate kinase-independent lysine synthesis in an extremely thermophilic bacterium, Thermus thermophilus: lysine is synthesized via alpha-aminoadipic acid not via diaminopimelic acid | journal = Journal of Bacteriology | volume = 181 | issue = 6 | pages = 1713–1718 | date = March 1999 | doi = 10.1128/JB.181.6.1713-1718.1999 | pmid = 10074061 | pmc = 93567 }}</ref><ref>{{cite journal | vauthors = Kosuge T, Hoshino T | title = The alpha-aminoadipate pathway for lysine biosynthesis is widely distributed among Thermus strains | journal = Journal of Bioscience and Bioengineering | volume = 88 | issue = 6 | pages = 672–675 | date = 1999 | pmid = 16232683 | doi = 10.1016/S1389-1723(00)87099-1 }}</ref><ref name="Nishida_1999">{{cite journal | vauthors = Nishida H, Nishiyama M, Kobashi N, Kosuge T, Hoshino T, Yamane H | title = A prokaryotic gene cluster involved in synthesis of lysine through the amino adipate pathway: a key to the evolution of amino acid biosynthesis | journal = Genome Research | volume = 9 | issue = 12 | pages = 1175–1183 | date = December 1999 | pmid = 10613839 | doi = 10.1101/gr.9.12.1175 | doi-access = free }}</ref> The first and ] in the AAA pathway is the condensation reaction between acetyl-CoA and α‑ketoglutarate catalysed by ] (E.C 2.3.3.14) to give the intermediate homocitryl‑CoA, which is ] by the same enzyme to produce ].<ref name="Nishida_2000">{{cite journal | vauthors = Nishida H, Nishiyama M | title = What is characteristic of fungal lysine synthesis through the alpha-aminoadipate pathway? | journal = Journal of Molecular Evolution | volume = 51 | issue = 3 | pages = 299–302 | date = September 2000 | pmid = 11029074 | doi = 10.1007/s002390010091 | bibcode = 2000JMolE..51..299N | s2cid = 1265909 }}</ref> Homocitrate is enzymatically ] by ] (E.C 4.2.1.36) to yield ].<ref>{{cite journal | vauthors = Zabriskie TM, Jackson MD | title = Lysine biosynthesis and metabolism in fungi | journal = Natural Product Reports | volume = 17 | issue = 1 | pages = 85–97 | date = February 2000 | pmid = 10714900 | doi = 10.1039/a801345d }}</ref> HAc then catalyses a second reaction in which ''cis''-homoaconitate undergoes ] to produce ].<ref name="Xu_2006" /> The resulting product undergoes an ] decarboxylation by ] (E.C 1.1.1.87) to yield α‑ketoadipate.<ref name="Xu_2006" /> AAA is then formed via a ]-dependent ] ] (E.C 2.6.1.39), using glutamate as the amino donor.<ref name="Nishida_2000" /> From this point on, the AAA pathway varies with on the kingdom. In fungi, AAA is reduced to α‑aminoadipate-semialdehyde via AAA reductase (E.C 1.2.1.95) in a unique process involving both ] and reduction that is activated by a ] (E.C 2.7.8.7).<ref name="Xu_2006" /> Once the semialdehyde is formed, ] ] (E.C 1.5.1.10) catalyses a condensation reaction with glutamate and NAD(P)H, as a proton donor, and the ] is reduced to produce the penultimate product, saccharopine.<ref name="Nishida_1999" /> The final step of the pathway in fungi involves the ] (E.C 1.5.1.8) catalysed oxidative ] of saccharopine, resulting in <small>L</small>-lysine.<ref name="Xu_2006" /> In a variant AAA pathway found in some prokaryotes, AAA is first converted to ''N''‑acetyl-α-aminoadipate, which is ] and then reductively ] to the ε-aldehyde.<ref name="Nishida_1999" /><ref name="Nishida_2000" /> The aldehyde is then ] to ''N''‑acetyllysine, which is deacetylated to give <small>L</small>-lysine.<ref name="Nishida_1999" /><ref name="Nishida_2000" /> However, the enzymes involved in this variant pathway need further validation.

==Catabolism==
]

As with all amino acids, ] of lysine is initiated from the uptake of dietary lysine or from the breakdown of ] protein. Catabolism is also used as a means to control the intracellular concentration of free lysine and maintain a ] to prevent the toxic effects of excessive free lysine.<ref name="Zhu_2004">{{cite journal | vauthors = Zhu X, Galili G | title = Lysine metabolism is concurrently regulated by synthesis and catabolism in both reproductive and vegetative tissues | journal = Plant Physiology | volume = 135 | issue = 1 | pages = 129–136 | date = May 2004 | pmid = 15122025 | pmc = 429340 | doi = 10.1104/pp.103.037168 }}</ref> There are several pathways involved in lysine catabolism but the most commonly used is the saccharopine pathway, which primarily takes place in the ] (and equivalent organs) in animals, specifically within the ].<ref name="Tomé_2007">{{cite journal | vauthors = Tomé D, Bos C | title = Lysine requirement through the human life cycle | journal = The Journal of Nutrition | volume = 137 | issue = 6 Suppl 2 | pages = 1642S–1645S | date = June 2007 | pmid = 17513440 | doi = 10.1093/jn/137.6.1642S | doi-access = free }}</ref><ref name="Zhu_2004" /><ref>{{cite journal | vauthors = Blemings KP, Crenshaw TD, Swick RW, Benevenga NJ | title = Lysine-alpha-ketoglutarate reductase and saccharopine dehydrogenase are located only in the mitochondrial matrix in rat liver | journal = The Journal of Nutrition | volume = 124 | issue = 8 | pages = 1215–1221 | date = August 1994 | pmid = 8064371 | doi = 10.1093/jn/124.8.1215 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Galili G, Tang G, Zhu X, Gakiere B | title = Lysine catabolism: a stress and development super-regulated metabolic pathway | journal = Current Opinion in Plant Biology | volume = 4 | issue = 3 | pages = 261–266 | date = June 2001 | pmid = 11312138 | doi = 10.1016/s1369-5266(00)00170-9 | bibcode = 2001COPB....4..261G }}</ref> This is the reverse of the previously described AAA pathway.<ref name="Tomé_2007" /><ref>{{cite journal | vauthors = Arruda P, Kemper EL, Papes F, Leite A | title = Regulation of lysine catabolism in higher plants | journal = Trends in Plant Science | volume = 5 | issue = 8 | pages = 324–330 | date = August 2000 | pmid = 10908876 | doi = 10.1016/s1360-1385(00)01688-5 }}</ref> In animals and plants, the first two steps of the saccharopine pathway are catalysed by the bifunctional enzyme, ], which possess both lysine-ketoglutarate reductase (LKR) (E.C 1.5.1.8) and SDH activities, whereas in other organisms, such as bacteria and fungi, both of these enzymes are encoded by separate ]s.<ref>{{cite journal | vauthors = Sacksteder KA, Biery BJ, Morrell JC, Goodman BK, Geisbrecht BV, Cox RP, Gould SJ, Geraghty MT | title = Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia | journal = American Journal of Human Genetics | volume = 66 | issue = 6 | pages = 1736–1743 | date = June 2000 | pmid = 10775527 | pmc = 1378037 | doi = 10.1086/302919 }}</ref><ref>{{cite journal | vauthors = Zhu X, Tang G, Galili G | title = The activity of the Arabidopsis bifunctional lysine-ketoglutarate reductase/saccharopine dehydrogenase enzyme of lysine catabolism is regulated by functional interaction between its two enzyme domains | journal = The Journal of Biological Chemistry | volume = 277 | issue = 51 | pages = 49655–49661 | date = December 2002 | pmid = 12393892 | doi = 10.1074/jbc.m205466200 | doi-access = free }}</ref> The first step involves the LKR catalysed reduction of <small>L</small>-lysine in the presence of α-ketoglutarate to produce saccharopine, with NAD(P)H acting as a proton donor.<ref name="Kiyota_2015">{{cite journal | vauthors = Kiyota E, Pena IA, Arruda P | title = The saccharopine pathway in seed development and stress response of maize | journal = Plant, Cell & Environment | volume = 38 | issue = 11 | pages = 2450–2461 | date = November 2015 | pmid = 25929294 | doi = 10.1111/pce.12563 | doi-access = free }}</ref> Saccharopine then undergoes a dehydration reaction, catalysed by SDH in the presence of ], to produce AAS and glutamate.<ref>{{cite journal | vauthors = Serrano GC, Rezende e Silva Figueira T, Kiyota E, Zanata N, Arruda P | title = Lysine degradation through the saccharopine pathway in bacteria: LKR and SDH in bacteria and its relationship to the plant and animal enzymes | journal = FEBS Letters | volume = 586 | issue = 6 | pages = 905–911 | date = March 2012 | pmid = 22449979 | doi = 10.1016/j.febslet.2012.02.023 | s2cid = 32385212 | doi-access = free | bibcode = 2012FEBSL.586..905D }}</ref> ] (E.C 1.2.1.31) then further dehydrates the molecule into AAA.<ref name="Kiyota_2015" /> Subsequently, PLP-AT catalyses the reverse reaction to that of the AAA biosynthesis pathway, resulting in AAA being converted to α-ketoadipate. The product, α‑ketoadipate, is decarboxylated in the presence of NAD<sup>+</sup> and coenzyme A to yield glutaryl-CoA, however the enzyme involved in this is yet to be fully elucidated.<ref name="Danhauser_2012">{{cite journal | vauthors = Danhauser K, Sauer SW, Haack TB, Wieland T, Staufner C, Graf E, Zschocke J, Strom TM, Traub T, Okun JG, Meitinger T, Hoffmann GF, Prokisch H, Kölker S | title = DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria | journal = American Journal of Human Genetics | volume = 91 | issue = 6 | pages = 1082–1087 | date = December 2012 | pmid = 23141293 | pmc = 3516599 | doi = 10.1016/j.ajhg.2012.10.006 }}</ref><ref>{{cite journal | vauthors = Sauer SW, Opp S, Hoffmann GF, Koeller DM, Okun JG, Kölker S | title = Therapeutic modulation of cerebral <small>L</small>-lysine metabolism in a mouse model for glutaric aciduria type I | journal = Brain | volume = 134 | issue = Pt 1 | pages = 157–170 | date = January 2011 | pmid = 20923787 | doi = 10.1093/brain/awq269 | doi-access = free }}</ref> Some evidence suggests that the 2-oxoadipate dehydrogenase complex (OADHc), which is structurally homologous to the E1 subunit of the ] (E.C 1.2.4.2), is responsible for the decarboxylation reaction.<ref name="Danhauser_2012" /><ref>{{cite journal | vauthors = Goncalves RL, Bunik VI, Brand MD | title = Production of superoxide/hydrogen peroxide by the mitochondrial 2-oxoadipate dehydrogenase complex | journal = Free Radical Biology & Medicine | volume = 91 | pages = 247–255 | date = February 2016 | pmid = 26708453 | doi = 10.1016/j.freeradbiomed.2015.12.020 | doi-access = free }}</ref> Finally, glutaryl-CoA is oxidatively decarboxylated to crotonyl-CoA by ] (E.C 1.3.8.6), which goes on to be further processed through multiple enzymatic steps to yield acetyl-CoA; an essential carbon ] involved in the ].<ref name="Kiyota_2015" /><ref>{{cite journal | vauthors = Goh DL, Patel A, Thomas GH, Salomons GS, Schor DS, Jakobs C, Geraghty MT | title = Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT) | journal = Molecular Genetics and Metabolism | volume = 76 | issue = 3 | pages = 172–180 | date = July 2002 | pmid = 12126930 | doi = 10.1016/s1096-7192(02)00037-9 }}</ref><ref>{{cite journal | vauthors = Härtel U, Eckel E, Koch J, Fuchs G, Linder D, Buckel W | title = Purification of glutaryl-CoA dehydrogenase from Pseudomonas sp., an enzyme involved in the anaerobic degradation of benzoate | journal = Archives of Microbiology | volume = 159 | issue = 2 | pages = 174–181 | date = 1993-02-01 | pmid = 8439237 | doi = 10.1007/bf00250279 | bibcode = 1993ArMic.159..174H | s2cid = 2262592 }}</ref><ref>{{cite journal | vauthors = Sauer SW | title = Biochemistry and bioenergetics of glutaryl-CoA dehydrogenase deficiency | journal = Journal of Inherited Metabolic Disease | volume = 30 | issue = 5 | pages = 673–680 | date = October 2007 | pmid = 17879145 | doi = 10.1007/s10545-007-0678-8 | s2cid = 20609879}}</ref>

== Nutritional value ==
Lysine is an essential amino acid in humans.<ref name="Nelson_2013">{{cite book |title=Lehninger principles of biochemistry | first1 = David L | last1 = Nelson | first2 = Michael M | last2 = Cox | first3 = Albert L | last3 = Lehninger | name-list-style = vanc |date=2013|publisher=W.H. Freeman and Company |isbn=978-1-4641-0962-1|edition=6th |location=New York|oclc=824794893}}</ref> The human daily nutritional requirement varies from ~60&nbsp;mg/kg in infancy to ~30&nbsp;mg/kg in adults.<ref name="Tomé_2007" /> This requirement is commonly met in a ] with the intake of ] well in excess of the recommended requirement.<ref name="Tomé_2007" /> In vegetarian diets, the intake of lysine is less due to the limited quantity of lysine in ] compared to meat sources.<ref name="Tomé_2007" />

Given the limiting concentration of lysine in cereal crops, it has long been speculated that the content of lysine can be increased through ] practices.<ref name="Galili_2013">{{cite journal | vauthors = Galili G, Amir R | title = Fortifying plants with the essential amino acids lysine and methionine to improve nutritional quality | journal = Plant Biotechnology Journal | volume = 11 | issue = 2 | pages = 211–222 | date = February 2013 | pmid = 23279001 | doi = 10.1111/pbi.12025 | doi-access = free }}</ref><ref name="Wang_2017">{{cite journal | vauthors = Wang G, Xu M, Wang W, Galili G | title = Fortifying Horticultural Crops with Essential Amino Acids: A Review | journal = International Journal of Molecular Sciences | volume = 18 | issue = 6 | pages = 1306 | date = June 2017 | pmid = 28629176 | pmc = 5486127 | doi = 10.3390/ijms18061306 | doi-access = free }}</ref> Often these practices have involved the intentional dysregulation of the DAP pathway by means of introducing lysine feedback-insensitive ] of the DHDPS enzyme.<ref name="Galili_2013" /><ref name="Wang_2017" /> These methods have met limited success likely due to the ] side effects of increased free lysine and indirect effects on the TCA cycle.<ref>{{cite journal | vauthors = Angelovici R, Fait A, Fernie AR, Galili G | title = A seed high-lysine trait is negatively associated with the TCA cycle and slows down Arabidopsis seed germination | journal = The New Phytologist | volume = 189 | issue = 1 | pages = 148–159 | date = January 2011 | pmid = 20946418 | doi = 10.1111/j.1469-8137.2010.03478.x | doi-access = free }}</ref> Plants accumulate lysine and other amino acids in the form of seed ]s, found within the seeds of the plant, and this represents the edible component of cereal crops.<ref>{{cite journal | vauthors = Edelman M, Colt M | title = Nutrient Value of Leaf vs. Seed | journal = Frontiers in Chemistry | volume = 4 | pages = 32 | date = 2016 | pmid = 27493937 | pmc = 4954856 | doi = 10.3389/fchem.2016.00032 | doi-access = free }}</ref> This highlights the need to not only increase free lysine, but also direct lysine towards the synthesis of stable seed storage proteins, and subsequently, increase the nutritional value of the consumable component of crops.<ref>{{cite journal | vauthors = Jiang SY, Ma A, Xie L, Ramachandran S | title = Improving protein content and quality by over-expressing artificially synthetic fusion proteins with high lysine and threonine constituent in rice plants | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 34427 | date = September 2016 | pmid = 27677708 | pmc = 5039639 | doi = 10.1038/srep34427 | bibcode = 2016NatSR...634427J }}</ref><ref name="Shewry_2007">{{Cite journal|last=Shewry|first=Peter R. | name-list-style = vanc |title=Improving the protein content and composition of cereal grain |journal=Journal of Cereal Science | date = November 2007 |volume=46|issue=3|pages=239–250|doi=10.1016/j.jcs.2007.06.006}}</ref> While genetic modification practices have met limited success, more traditional ] techniques have allowed for the isolation of "]", which has significantly increased levels of lysine and ], also an essential amino acid. This increase in lysine content is attributed to an ''opaque-2'' mutation that reduced the ] of lysine-lacking ]-related seed storage proteins and, as a result, increased the abundance of other proteins that are rich in lysine.<ref name="Shewry_2007" /><ref>{{Cite journal | vauthors = Prasanna B, Vasal SK, Kassahun B, Singh NN |date=2001|title=Quality protein maize| jstor = 24105845 |journal=Current Science|volume=81|issue=10|pages=1308–1319}}</ref> Commonly, to overcome the limiting abundance of lysine in ] feed, industrially produced lysine is added.<ref name="Kircher_2001">{{cite journal | vauthors = Kircher M, Pfefferle W | title = The fermentative production of <small>L</small>-lysine as an animal feed additive | journal = Chemosphere | volume = 43 | issue = 1 | pages = 27–31 | date = April 2001 | pmid = 11233822 | doi = 10.1016/s0045-6535(00)00320-9 | bibcode = 2001Chmsp..43...27K }}</ref><ref>{{Cite journal|last1=Junior|first1=Letti|last2=Alberto|first2=Luiz|last3=Letti|first3=Gilberto Vinícius Melo|last4=Soccol|first4=Carlos Ricardo|last5=Junior|first5=Letti|last6=Alberto|first6=Luiz|last7=Letti|first7=Gilberto Vinícius Melo|last8=Soccol|first8=Carlos Ricardo | name-list-style = vanc |date=2016|title=Development of an <small>L</small>-Lysine Enriched Bran for Animal Nutrition via Submerged Fermentation by Corynebacterium glutamicum using Agroindustrial Substrates|journal=Brazilian Archives of Biology and Technology|volume=59|doi=10.1590/1678-4324-2016150519|issn=1516-8913|doi-access=free}}</ref> The industrial process includes the ] culturing of '']'' and the subsequent purification of lysine.<ref name="Kircher_2001" />

=== Dietary sources ===
Good sources of lysine are high-protein foods such as eggs, meat (specifically red meat, lamb, pork, and poultry), ], beans and peas, cheese (particularly Parmesan), and certain fish (such as ] and ]s).<ref>{{cite web|url=http://www.umm.edu/altmed/articles/lysine-000312.htm|title=Lysine|author=University of Maryland Medical Center|access-date=2009-12-30}}</ref> Lysine is the ] (the essential amino acid found in the smallest quantity in the particular foodstuff) in most ]s, but is plentiful in most ] (legumes).<ref name="VRYoung">{{cite journal|vauthors=Young VR, Pellett PL|year=1994|title=Plant proteins in relation to human protein and amino acid nutrition|journal=American Journal of Clinical Nutrition|volume=59|issue=5&nbsp;Suppl|pages=1203S–1212S|doi=10.1093/ajcn/59.5.1203s|pmid=8172124|s2cid=35271281|doi-access=free}}</ref> Beans contain the lysine that ] lacks, and in the human archeological record beans and maize often appear together, as in the ]: beans, maize, and squash.<ref>{{cite journal |title=The 'How' of the Three Sisters: The Origins of Agriculture in Mesoamerica and the Human Niche |first=Amanda J. |last=Landon |url=https://digitalcommons.unl.edu/nebanthro/40/ |accessdate=9 August 2022 |year=2008 |journal=Nebraska Anthropologist |pages=110–124}}</ref>

A food is considered to have sufficient lysine if it has at least 51&nbsp;mg of lysine per gram of protein (so that the protein is 5.1% lysine).<ref>{{cite book|url=https://www.nap.edu/read/10490/chapter/12|title=Dietary Reference Intakes for Macronutrients|author=Institute of Medicine of the National Academies|year=2005|page=589|doi=10.17226/10490|isbn=978-0-309-08525-0|access-date=2017-10-29}}</ref> <small>L</small>-lysine HCl is used as a ], providing 80.03% <small>L</small>-lysine.<ref name="DSBI">{{cite web|url=https://www.cdc.gov/nchs/nhanes/nhanes1999-2000/DSBI.htm|title=Dietary Supplement Database: Blend Information (DSBI)|quote=<small>L</small>-Lysine HCl 10000820 80.03% lysine}}</ref> As such, 1&nbsp;g of <small>L</small>-lysine is contained in 1.25&nbsp;g of <small>L</small>-lysine HCl.

== Biological roles ==
The most common role for lysine is proteinogenesis. Lysine frequently plays an important role in ]. Since its side chain contains a positively charged group on one end and a long ] carbon tail close to the backbone, lysine is considered somewhat ]. For this reason, lysine can be found buried as well as more commonly in solvent channels and on the exterior of proteins, where it can interact with the aqueous environment.<ref name="Betts_2003">{{Cite book|title=Bioinformatics for Geneticists|last1=Betts|first1=Matthew J.|last2=Russell|first2=Robert B. | name-list-style = vanc |date=2003|publisher=John Wiley & Sons, Ltd|isbn=978-0-470-86730-3|editor-last=Barnes|editor-first=Michael R.|pages=289–316|doi=10.1002/0470867302.ch14|editor-last2=Gray|editor-first2=Ian C. }}</ref> Lysine can also contribute to protein stability as its ε-amino group often participates in ]ing, ] and ] interactions to form a ].<ref name="Betts_2003" /><ref>{{cite journal | vauthors = Blickling S, Renner C, Laber B, Pohlenz HD, Holak TA, Huber R | title = Reaction mechanism of Escherichia coli dihydrodipicolinate synthase investigated by X-ray crystallography and NMR spectroscopy | journal = Biochemistry | volume = 36 | issue = 1 | pages = 24–33 | date = January 1997 | pmid = 8993314 | doi = 10.1021/bi962272d | s2cid = 23072673 }}</ref><ref>{{cite journal | vauthors = Kumar S, Tsai CJ, Nussinov R | title = Factors enhancing protein thermostability | journal = Protein Engineering | volume = 13 | issue = 3 | pages = 179–91 | date = March 2000 | pmid = 10775659 | doi = 10.1093/protein/13.3.179 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sokalingam S, Raghunathan G, Soundrarajan N, Lee SG | title = A study on the effect of surface lysine to arginine mutagenesis on protein stability and structure using green fluorescent protein | journal = PLOS ONE | volume = 7 | issue = 7 | pages = e40410 | date = 2012-07-09 | pmid = 22792305 | pmc = 3392243 | doi = 10.1371/journal.pone.0040410 | bibcode = 2012PLoSO...740410S | doi-access = free }}</ref>

A second major role of lysine is in ] regulation by means of ] ].<ref name="Dambacher_2010">{{cite journal | vauthors = Dambacher S, Hahn M, Schotta G | title = Epigenetic regulation of development by histone lysine methylation | journal = Heredity | volume = 105 | issue = 1 | pages = 24–37 | date = July 2010 | pmid = 20442736 | doi = 10.1038/hdy.2010.49 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Martin C, Zhang Y | title = The diverse functions of histone lysine methylation | journal = Nature Reviews. Molecular Cell Biology | volume = 6 | issue = 11 | pages = 838–849 | date = November 2005 | pmid = 16261189 | doi = 10.1038/nrm1761 | s2cid = 31300025 }}</ref> There are several types of covalent histone modifications, which commonly involve lysine residues found in the protruding tail of histones. Modifications often include the addition or removal of an ] forming ] or reverting to lysine, up to three ], ] or a ] group.<ref name="Dambacher_2010" /><ref>{{cite journal | vauthors = Black JC, Van Rechem C, Whetstine JR | title = Histone lysine methylation dynamics: establishment, regulation, and biological impact | journal = Molecular Cell | volume = 48 | issue = 4 | pages = 491–507 | date = November 2012 | pmid = 23200123 | pmc = 3861058 | doi = 10.1016/j.molcel.2012.11.006 }}</ref><ref>{{cite journal | vauthors = Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M | title = Lysine acetylation targets protein complexes and co-regulates major cellular functions | journal = Science | volume = 325 | issue = 5942 | pages = 834–840 | date = August 2009 | pmid = 19608861 | doi = 10.1126/science.1175371 | bibcode = 2009Sci...325..834C | s2cid = 206520776 | url = https://semanticscholar.org/paper/af946911954f7ec506e0afa6faec466ece09b117 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Shiio Y, Eisenman RN | title = Histone sumoylation is associated with transcriptional repression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 23 | pages = 13225–13230 | date = November 2003 | pmid = 14578449 | pmc = 263760 | doi = 10.1073/pnas.1735528100 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, Jones RS, Zhang Y | title = Role of histone H2A ubiquitination in Polycomb silencing | journal = Nature | volume = 431 | issue = 7010 | pages = 873–878 | date = October 2004 | pmid = 15386022 | doi = 10.1038/nature02985 | bibcode = 2004Natur.431..873W | hdl = 10261/73732 | s2cid = 4344378}}</ref> The various modifications have downstream effects on ], in which genes can be activated or repressed.

Lysine has also been implicated to play a key role in other biological processes including; structural proteins of ]s, ] ], and ].<ref name="Shoulders_2009">{{cite journal | vauthors = Shoulders MD, Raines RT | title = Collagen structure and stability | journal = Annual Review of Biochemistry | volume = 78 | pages = 929–958 | date = 2009 | pmid = 19344236 | pmc = 2846778 | doi = 10.1146/annurev.biochem.77.032207.120833 }}</ref><ref name="Civitelli_1992">{{cite journal | vauthors = Civitelli R, Villareal DT, Agnusdei D, Nardi P, Avioli LV, Gennari C | title = Dietary <small>L</small>-lysine and calcium metabolism in humans | journal = Nutrition | volume = 8 | issue = 6 | pages = 400–405 | date = 1992 | pmid = 1486246 }}</ref><ref name="Vaz_2002">{{cite journal | vauthors = Vaz FM, Wanders RJ | title = Carnitine biosynthesis in mammals | journal = The Biochemical Journal | volume = 361 | issue = Pt 3 | pages = 417–429 | date = February 2002 | pmid = 11802770 | pmc = 1222323 | doi = 10.1042/bj3610417 }}</ref> Lysine has been shown to be involved in the ] between the three ] in ], resulting in its stability and tensile strength.<ref name="Shoulders_2009" /><ref>{{cite journal | vauthors = Yamauchi M, Sricholpech M | title = Lysine post-translational modifications of collagen | journal = Essays in Biochemistry | volume = 52 | pages = 113–133 | date = 2012-05-25 | pmid = 22708567 | pmc = 3499978 | doi = 10.1042/bse0520113 }}</ref> This mechanism is akin to the role of lysine in ], in which lysine (and ''meso''-diaminopimelate) are critical to the formation of crosslinks, and therefore, stability of the cell wall.<ref>{{cite journal | vauthors = Vollmer W, Blanot D, de Pedro MA | title = Peptidoglycan structure and architecture | journal = FEMS Microbiology Reviews | volume = 32 | issue = 2 | pages = 149–167 | date = March 2008 | pmid = 18194336 | doi = 10.1111/j.1574-6976.2007.00094.x | doi-access = free }}</ref> This concept has previously been explored as a means to circumvent the unwanted release of potentially ] genetically modified bacteria. It was proposed that an ] strain of '']'' (<sub>X</sub>1776) could be used for all genetic modification practices, as the strain is unable to survive without the supplementation of DAP, and thus, cannot live outside of a laboratory environment.<ref>{{cite journal | vauthors = Curtiss R | title = Biological containment and cloning vector transmissibility | journal = The Journal of Infectious Diseases | volume = 137 | issue = 5 | pages = 668–675 | date = May 1978 | pmid = 351084 | doi = 10.1093/infdis/137.5.668 }}</ref> Lysine has also been proposed to be involved in calcium intestinal absorption and renal retention, and thus, may play a role in ].<ref name="Civitelli_1992" /> Finally, lysine has been shown to be a precursor for ], which transports fatty acids to the ], where they can be oxidised for the release of energy.<ref name="Vaz_2002" /><ref name="Rudman_1977">{{cite journal | vauthors = Flanagan JL, Simmons PA, Vehige J, Willcox MD, Garrett Q | title = Role of carnitine in disease | journal = Nutrition & Metabolism | volume = 7 | pages = 30 | date = April 2010 | pmid = 20398344 | pmc = 2861661 | doi = 10.1186/1743-7075-7-30 | doi-access = free }}</ref> Carnitine is synthesised from ], which is a product of the degradation of certain proteins, as such lysine must first be incorporated into proteins and be methylated prior to being converted to carnitine.<ref name="Vaz_2002" /> However, in mammals the primary source of carnitine is through dietary sources, rather than through lysine conversion.<ref name="Vaz_2002" />

In ] like ] and the visual opsins (encoded by the genes ], ], and ]), ] forms a ] with a conserved lysine residue, and interaction of light with the ] group causes signal transduction in ] (See ] for details).

=== Disputed roles ===
There has been a long discussion that lysine, when administered intravenously or orally, can significantly increase the release of ]s.<ref name="Chromiak_2002">{{cite journal | vauthors = Chromiak JA, Antonio J | title = Use of amino acids as growth hormone-releasing agents by athletes | journal = Nutrition | year = 2002 | volume = 18 | issue = 7–8 | pages = 657–661 | pmid = 12093449 | doi = 10.1016/s0899-9007(02)00807-9 }}</ref> This has led to athletes using lysine as a means of promoting muscle growth while training, however, no significant evidence to support this application of lysine has been found to date.<ref name="Chromiak_2002" /><ref>{{cite journal | vauthors = Corpas E, Blackman MR, Roberson R, Scholfield D, Harman SM | title = Oral arginine-lysine does not increase growth hormone or insulin-like growth factor-I in old men | journal = Journal of Gerontology | volume = 48 | issue = 4 | pages = M128–M133 | date = July 1993 | pmid = 8315224 | doi = 10.1093/geronj/48.4.M128 }}</ref>

Because ] (HSV) proteins are richer in arginine and poorer in lysine than the cells they infect, lysine supplements have been tried as a treatment. Since the two amino acids are taken up in the intestine, reclaimed in the kidney, and moved into cells by the same ]s, an abundance of lysine would, in theory, limit the amount of arginine available for viral replication.<ref name="pmid16813459">{{cite journal| author=Gaby AR| title=Natural remedies for Herpes simplex. | journal=Altern Med Rev | year= 2006 | volume= 11 | issue= 2 | pages= 93–101 | pmid=16813459 }}</ref> Clinical studies do not provide good evidence for effectiveness as a ] or in the treatment for HSV outbreaks.<ref name="pmid11225166">{{cite journal| author=Tomblin FA, Lucas KH| title=Lysine for management of herpes labialis. | journal=Am J Health Syst Pharm | year= 2001 | volume= 58 | issue= 4 | pages= 298–300, 304 | pmid=11225166 | doi= 10.1093/ajhp/58.4.298| url=https://www.medscape.com/viewarticle/406943 | doi-access=free }}</ref><ref>{{cite journal | vauthors = Chi CC, Wang SH, Delamere FM, Wojnarowska F, Peters MC, Kanjirath PP | title = Interventions for prevention of herpes simplex labialis (cold sores on the lips) | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD010095 | date = 7 August 2015 | volume = 2016 | pmid = 26252373 | doi = 10.1002/14651858.CD010095.pub2 | pmc = 6461191 }}</ref> In response to product claims that lysine could improve immune responses to HSV, a review by the ] found no evidence of a cause–effect relationship. The same review, published in 2011, found no evidence to support claims that lysine could lower cholesterol, increase appetite, contribute to protein synthesis in any role other than as an ordinary nutrient, or increase calcium absorption or retention.<ref>{{cite journal|title=Scientific Opinion on the substantiation of health claims related to <small>L</small>-lysine and immune defence against herpes virus (ID 453), maintenance of normal blood LDL-cholesterol concentrations (ID 454, 4669), increase in appetite leading to an increase in energ|journal=EFSA Journal|volume=9|issue=4|year=2011|pages=2063|issn=1831-4732|doi=10.2903/j.efsa.2011.2063}}</ref>

== Roles in disease ==
Diseases related to lysine are a result of the downstream processing of lysine, i.e. the incorporation into proteins or modification into alternative biomolecules. The role of lysine in collagen has been outlined above, however, a lack of lysine and ] involved in the crosslinking of collagen peptides has been linked to a disease state of the connective tissue.<ref>{{cite journal | vauthors = Pinnell SR, Krane SM, Kenzora JE, Glimcher MJ | title = A heritable disorder of connective tissue. Hydroxylysine-deficient collagen disease | journal = The New England Journal of Medicine | volume = 286 | issue = 19 | pages = 1013–1020 | date = May 1972 | pmid = 5016372 | doi = 10.1056/NEJM197205112861901 }}</ref> As carnitine is a key lysine-derived metabolite involved in fatty acid metabolism, a substandard diet lacking sufficient carnitine and lysine can lead to decreased carnitine levels, which can have significant cascading effects on an individual's health.<ref name="Rudman_1977" /><ref>{{cite journal | vauthors = Rudman D, Sewell CW, Ansley JD | title = Deficiency of carnitine in cachectic cirrhotic patients | journal = The Journal of Clinical Investigation | volume = 60 | issue = 3 | pages = 716–723 | date = September 1977 | pmid = 893675 | pmc = 372417 | doi = 10.1172/jci108824 }}</ref> Lysine has also been shown to play a role in ], as lysine is suspected to have an effect on the uptake of ] and, subsequently, the concentration of ] in ].<ref name="Rushton_2002">{{cite journal | vauthors = Rushton DH | title = Nutritional factors and hair loss | journal = Clinical and Experimental Dermatology | volume = 27 | issue = 5 | pages = 396–404 | date = July 2002 | pmid = 12190640 | doi = 10.1046/j.1365-2230.2002.01076.x | s2cid = 39327815 }}</ref> However, the exact mechanism of action is yet to be elucidated.<ref name="Rushton_2002" /> Most commonly, lysine deficiency is seen in non-western societies and manifests as ], which has profound and systemic effects on the health of the individual.<ref>{{cite journal | vauthors = Emery PW | title = Metabolic changes in malnutrition | journal = Eye | volume = 19 | issue = 10 | pages = 1029–1034 | date = October 2005 | pmid = 16304580 | doi = 10.1038/sj.eye.6701959 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ghosh S, Smriga M, Vuvor F, Suri D, Mohammed H, Armah SM, Scrimshaw NS | title = Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana | journal = The American Journal of Clinical Nutrition | volume = 92 | issue = 4 | pages = 928–939 | date = October 2010 | pmid = 20720257 | doi = 10.3945/ajcn.2009.28834 | doi-access = free }}</ref> There is also a ] genetic disease that involves ]s in the enzymes responsible for lysine catabolism, namely the bifunctional AASS enzyme of the saccharopine pathway.<ref name="Houten_2013">{{cite journal | vauthors = Houten SM, Te Brinke H, Denis S, Ruiter JP, Knegt AC, de Klerk JB, Augoustides-Savvopoulou P, Häberle J, Baumgartner MR, Coşkun T, Zschocke J, Sass JO, Poll-The BT, Wanders RJ, Duran M | title = Genetic basis of hyperlysinemia | journal = Orphanet Journal of Rare Diseases | volume = 8 | pages = 57 | date = April 2013 | pmid = 23570448 | pmc = 3626681 | doi = 10.1186/1750-1172-8-57 | doi-access = free }}</ref> Due to a lack of lysine catabolism, the amino acid accumulates in plasma and patients develop ], which can present as asymptomatic to severe ], including ], ], ], and ].<ref name="Houten_2013" /><ref>{{Cite book|title=Inborn Metabolic Diseases|last1=Hoffmann|first1=Georg F.|last2=Kölker|first2=Stefan |chapter=Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism | name-list-style = vanc |date=2016|publisher=Springer, Berlin, Heidelberg|isbn=978-3-662-49769-2|pages=333–348|doi=10.1007/978-3-662-49771-5_22}}</ref> The clinical significance of hyperlysinemia is the subject of debate in the field with some studies finding no correlation between physical or mental disabilities and hyperlysinemia.<ref>{{cite journal | vauthors = Dancis J, Hutzler J, Ampola MG, Shih VE, van Gelderen HH, Kirby LT, Woody NC | title = The prognosis of hyperlysinemia: an interim report | journal = American Journal of Human Genetics | volume = 35 | issue = 3 | pages = 438–442 | date = May 1983 | pmid = 6407303 | pmc = 1685659 }}</ref> In addition to this, mutations in genes related to lysine metabolism have been implicated in several disease states, including ] (]), ] (]), and ] (]).<ref name="Danhauser_2012" /><ref>{{cite journal | vauthors = Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MA, Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT | title = Mutations in antiquitin in individuals with pyridoxine-dependent seizures | journal = Nature Medicine | volume = 12 | issue = 3 | pages = 307–309 | date = March 2006 | pmid = 16491085 | doi = 10.1038/nm1366 | s2cid = 27940375 }}</ref><ref>{{cite journal | vauthors = Mills PB, Footitt EJ, Mills KA, Tuschl K, Aylett S, Varadkar S, Hemingway C, Marlow N, Rennie J, Baxter P, Dulac O, Nabbout R, Craigen WJ, Schmitt B, Feillet F, Christensen E, De Lonlay P, Pike MG, Hughes MI, Struys EA, Jakobs C, Zuberi SM, Clayton PT | title = Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency) | journal = Brain | volume = 133 | issue = Pt 7 | pages = 2148–2159 | date = July 2010 | pmid = 20554659 | pmc = 2892945 | doi = 10.1093/brain/awq143 }}</ref><ref>{{cite journal | vauthors = Hagen J, te Brinke H, Wanders RJ, Knegt AC, Oussoren E, Hoogeboom AJ, Ruijter GJ, Becker D, Schwab KO, Franke I, Duran M, Waterham HR, Sass JO, Houten SM | title = Genetic basis of alpha-aminoadipic and alpha-ketoadipic aciduria | journal = Journal of Inherited Metabolic Disease | volume = 38 | issue = 5 | pages = 873–879 | date = September 2015 | pmid = 25860818 | doi = 10.1007/s10545-015-9841-9 | s2cid = 20379124 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hedlund GL, Longo N, Pasquali M | title = Glutaric acidemia type 1 | journal = American Journal of Medical Genetics Part C: Seminars in Medical Genetics | volume = 142C | issue = 2 | pages = 86–94 | date = May 2006 | pmid = 16602100 | pmc = 2556991 | doi = 10.1002/ajmg.c.30088 }}</ref>

Hyperlysinuria is marked by high amounts of lysine in the urine.<ref>{{cite web |url=http://dictionary.reference.com/browse/hyperlysinuria |title=Hyperlysinuria &#124; Define Hyperlysinuria at Dictionary.com }}</ref> It is often due to a ] in which a ] involved in the breakdown of lysine is non functional due to a genetic mutation.<ref name=Book06/> It may also occur due to a failure of ] tubular transport.<ref name=Book06>{{cite book |author1=Walter, John |author2=John Fernandes |author3=Jean-Marie Saudubray |author4=Georges van den Berghe |title=Inborn Metabolic Diseases: Diagnosis and Treatment |publisher=Springer |location=Berlin |year=2006 |pages=296 |isbn=978-3-540-28783-4 }}</ref>

==Use of lysine in animal feed==
]

Lysine production for animal feed is a major global industry, reaching in 2009 almost 700,000 tons for a market value of over €1.22&nbsp;billion.<ref name=lysineanimalfeed1>{{cite web | url = http://www.allaboutfeed.net/news/norwegian-granted-for-improving-lysine-production-process-id4052.html | archive-url=https://web.archive.org/web/20120311103403/http://www.allaboutfeed.net/news/norwegian-granted-for-improving-lysine-production-process-id4052.html | archive-date = 11 March 2012 | url-status = dead | title = Norwegian granted for improving lysine production process | date = 26 January 2010 | work = All About Feed }}</ref> Lysine is an important additive to animal feed because it is a limiting amino acid when optimizing the growth of certain animals such as pigs and chickens for the production of meat. Lysine supplementation allows for the use of lower-cost plant protein (maize, for instance, rather than ]) while maintaining high growth rates, and limiting the pollution from nitrogen excretion.<ref name=lysineanimalfeed>{{cite book | vauthors = Toride Y | chapter = Lysine and other amino acids for feed: production and contribution to protein utilization in animal feeding | chapter-url = http://www.fao.org/docrep/007/y5019e/y5019e0a.htm | title = Protein sources for the animal feed industry; FAO Expert Consultation and Workshop on Protein Sources for the Animal Feed Industry; Bangkok, 29 April - 3 May 2002 | date = 2004 | publisher = Food and Agriculture Organization of the United Nations | location = Rome | isbn = 978-92-5-105012-5 |url-status=live |archive-url=https://web.archive.org/web/20190201183109/http://www.fao.org/docrep/007/y5019e/y5019e0a.htm |archive-date= Feb 1, 2019 }}</ref> In turn, however, phosphate pollution is a major environmental cost when corn is used as feed for poultry and swine.<ref>{{cite journal | vauthors = Abelson PH | title = A potential phosphate crisis | journal = Science | volume = 283 | issue = 5410 | pages = 2015 | date = March 1999 | pmid = 10206902 | doi = 10.1126/science.283.5410.2015 | bibcode = 1999Sci...283.2015A | s2cid = 28106949 |bibcode-access=free |s2cid-access=free |doi-access=free }}</ref>

Lysine is industrially produced by microbial fermentation, from a base mainly of sugar. Genetic engineering research is actively pursuing bacterial strains to improve the efficiency of production and allow lysine to be made from other substrates.<ref name=lysineanimalfeed1/> The most common bacteria used is ] specially mutagenized or gene-engineered to produce lysine, but analogous strains of ] are also employed.

==In popular culture==
The 1993 film '']'', which is based on the 1990 novel '']'' by ], features ]s that were ] so that they could not produce lysine, an example of engineered ].<ref>{{cite news | last = Coyne | first = Jerry A. | name-list-style = vanc | title = The Truth Is Way Out There | work = ] | date = 10 October 1999 | url = https://query.nytimes.com/gst/fullpage.html?res=9E0DE6D7153EF933A25753C1A96F958260 |url-access=subscription | access-date = 2008-04-06 |url-status=live |archive-url=https://web.archive.org/web/20121110071830/http://www.nytimes.com/1999/10/10/books/the-truth-is-way-out-there.html |archive-date= Nov 10, 2012 }}</ref> This was known as the "lysine contingency" and was supposed to prevent the ] dinosaurs from surviving outside the park, forcing them to depend on lysine supplements provided by the park's veterinary staff. In reality, no animal can produce lysine; it is an ].<ref>{{cite journal | vauthors = Wu G | title = Amino acids: metabolism, functions, and nutrition | journal = Amino Acids | volume = 37 | issue = 1 | pages = 1–17 | date = May 2009 | pmid = 19301095 | doi = 10.1007/s00726-009-0269-0 | s2cid = 1870305 }}</ref>

In 1996, lysine became the focus of a ], the largest in United States history. The ] paid a fine of US$100&nbsp;million, and three of its executives were convicted and served prison time. Also found guilty in the price-fixing case were two Japanese firms (], Kyowa Hakko) and a South Korean firm (Sewon).<ref>{{cite book | vauthors = Connor JM | title = Global Price Fixing | edition = 2nd | publisher = Springer-Verlag | location = Heidelberg | year = 2008 | isbn = 978-3-540-78669-6 }}</ref> Secret video recordings of the conspirators fixing lysine's price can be found online or by requesting the video from the ], Antitrust Division. This case gave the basis for the book '']'',<ref>{{cite book | last = Eichenwald | first = Kurt | name-list-style = vanc | title = The Informant: a true story | publisher = Broadway Books | location = New York | date = 2000 | isbn = 978-0-7679-0326-4 | url-access = registration | url = https://archive.org/details/informanttruest00eich }}</ref> and the movie '']''.

== References ==
{{Academic peer reviewed|Q55120301|doi-access=free }}
{{Reflist}}

{{Amino acids}}
{{Amino acid metabolism intermediates}}

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