Editing Lysine (section)

== Biological roles ==
The most common role for lysine is proteinogenesis. Lysine frequently plays an important role in [[protein structure]]. Since its side chain contains a positively charged group on one end and a long [[Hydrophobe|hydrophobic]] carbon tail close to the backbone, lysine is considered somewhat [[Amphiphile|amphipathic]]. 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 [[hydrogen bond]]ing, [[Salt bridge (protein and supramolecular)|salt bridges]] and [[Covalent bond|covalent]] interactions to form a [[Schiff base]].<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 [[Epigenetics|epigenetic]] regulation by means of [[histone]] [[Histone#Histone modification|modification]].<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 [[Acetylation|acetyl (−CH<sub>3</sub>CO)]] forming [[acetyllysine]] or reverting to lysine, up to three [[Methylation|methyl (−CH<sub>3</sub>)]], [[Ubiquitin#Ubiquitylation|ubiquitin]] or a [[SUMO protein|sumo protein]] 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 [[Regulation of gene expression|gene regulation]], 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 [[connective tissue]]s, [[calcium]] [[homeostasis]], and [[fatty acid metabolism]].<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 [[Cross-link|crosslinking]] between the three [[Alpha helix|helical polypeptides]] in [[collagen]], 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 [[Bacterial cell structure#Cell wall|bacterial cell walls]], 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 [[Pathogen#Bacteria|pathogenic]] genetically modified bacteria. It was proposed that an [[Auxotrophy|auxotrophic]] strain of ''[[Escherichia coli]]'' (<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 [[Calcium metabolism|calcium homeostasis]].<ref name="Civitelli_1992" /> Finally, lysine has been shown to be a precursor for [[carnitine]], which transports fatty acids to the [[mitochondria]], 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 [[methyllysine|trimethyllysine]], 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 [[opsins]] like [[rhodopsin]] and the visual opsins (encoded by the genes [[OPN1SW]], [[OPN1MW]], and [[OPN1LW]]), [[retinaldehyde]] forms a [[Schiff base]] with a conserved lysine residue, and interaction of light with the [[retinylidene]] group causes signal transduction in [[color vision]] (See [[visual cycle]] for details).

=== Disputed roles ===
There has been a long discussion that lysine, when administered intravenously or orally, can significantly increase the release of [[growth hormone]]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 [[herpes simplex virus]] (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 [[amino acid transporter]]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 [[Preventive healthcare|prophylactic]] 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 [[European Food Safety Authority]] 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 energy intake...|journal=EFSA Journal|volume=9|issue=4|year=2011|pages=2063|issn=1831-4732|doi=10.2903/j.efsa.2011.2063}}</ref>