Editing Amino acid (section)

==General structure==
[[File:ProteinogenicAminoAcids.svg|thumb|upright=2.75|The 21 [[Proteinogenic amino acid|proteinogenic α-amino acids]] found in [[eukaryote]]s, grouped according to their side chains' [[PKa|p''K''<sub>a</sub>]] values and charges carried at [[PH#Living systems|physiological pH (7.4)]]]]
'''2-''', '''alpha-''', or '''α-amino acids'''<ref>{{cite web |url=http://www.merriam-webster.com/medical/alpha-amino%20acid |title=Alpha amino acid |work=Merriam-Webster Medical |access-date=3 January 2015|archive-date=3 January 2015|archive-url=https://web.archive.org/web/20150103191856/http://www.merriam-webster.com/medical/alpha-amino%20acid|url-status=live}}.</ref> have the generic [[Chemical formula|formula]] {{chem2|H2NCHRCOOH}} in most cases,{{efn|[[Proline]] and other cyclic amino acids are an exception to this general formula. Cyclization of the α-amino acid creates the corresponding secondary amine. These are occasionally referred to as [[imino acid]]s.}} where R is an [[organic chemistry|organic]] [[substituent]] known as a "[[Substituent|side chain]]".<ref>{{Cite web | vauthors = Clark J |date=August 2007 |title=An introduction to amino acids |url=http://www.chemguide.co.uk/organicprops/aminoacids/background.html |website=chemguide |access-date=4 July 2015 |url-status=live |archive-date=30 April 2015|archive-url=https://web.archive.org/web/20150430051143/http://www.chemguide.co.uk/organicprops/aminoacids/background.html}}</ref>

Of the many hundreds of described amino acids, 22 are [[Proteinogenic amino acid|proteinogenic]] ("protein-building").<ref>{{cite encyclopedia |year=2008|title=Amino acids |encyclopedia=Peptides from A to Z: A Concise Encyclopedia |url=https://books.google.com/books?id=doe9NwgJTAsC&pg=PA20 |publisher=Wiley-VCH|location=Germany|isbn=9783527621170 |via=Google Books|page=20| vauthors = Jakubke HD, Sewald N |access-date=5 January 2016|archive-date=17 May 2016|archive-url = https://web.archive.org/web/20160517144350/https://books.google.com/books?id=doe9NwgJTAsC&pg=PA20|url-status = live}}</ref><ref>{{cite book | veditors = Pollegioni L, Servi S | title = Unnatural Amino Acids: Methods and Protocols|year = 2012|publisher = Humana Press|isbn = 978-1-61779-331-8|page = v|oclc = 756512314|series = Methods in Molecular Biology |volume=794|doi = 10.1007/978-1-61779-331-8|s2cid = 3705304 }}</ref><ref>{{cite journal | vauthors = Hertweck C | title = Biosynthesis and charging of pyrrolysine, the 22nd genetically encoded amino acid | journal = Angewandte Chemie | volume = 50 | issue = 41 | pages = 9540–9541 | date = October 2011 | pmid = 21796749 | doi = 10.1002/anie.201103769 | s2cid = 5359077 }}{{Closed access}}
</ref> It is these 22 compounds that combine to give a vast array of peptides and proteins assembled by [[ribosome]]s.<ref name="NIGMS">{{cite web |title=Chapter 1: Proteins are the Body's Worker Molecules |date=27 October 2011 |website=The Structures of Life |publisher=National Institute of General Medical Sciences |url=https://publications.nigms.nih.gov/structlife/chapter1.html |access-date=20 May 2008 |archive-date=7 June 2014 |archive-url=https://web.archive.org/web/20140607084902/https://publications.nigms.nih.gov/structlife/chapter1.html}}</ref> Non-proteinogenic or modified amino acids may arise from [[post-translational modification]] or during [[nonribosomal peptide]] synthesis.

===Chirality===
The [[carbon]] atom next to the [[carboxyl group]] is called the [[alpha carbon|α–carbon]]. In proteinogenic amino acids, it bears the amine and the R group or [[Substituent|side chain]] specific to each amino acid, as well as a hydrogen atom. With the exception of glycine, for which the side chain is also a hydrogen atom, the α–carbon is [[stereogenic]]. All [[chiral]] proteogenic amino acids have the <small>L</small> configuration. They are "left-handed" [[enantiomer]]s, which refers to the [[stereoisomers]] of the alpha carbon.

A few <small>D</small>-amino acids ("right-handed") have been found in nature, e.g., in [[bacterial envelope]]s, as a [[Neuromodulation|neuromodulator]] (<small>D</small>-[[serine]]), and in some [[antibiotic]]s.<ref>{{cite book | title = Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology | publisher = Wiley-Blackwell | year = 2012 | isbn = 978-0-470-14684-2 | location = Oxford | veditors = Michal G, Schomburg D | page = 5 | edition = 2nd }}</ref><ref name="Creighton">{{Cite book | vauthors = Creighton TH |title=Proteins: structures and molecular properties |publisher=W. H. Freeman |location=San Francisco |year=1993 |chapter=Chapter 1 |isbn=978-0-7167-7030-5 |chapter-url-access=registration |chapter-url=https://archive.org/details/proteinsstructur0000crei }}</ref> Rarely, [[D-Amino acid|<small>D</small>-amino acid residues]] are found in proteins, and are converted from the <small>L</small>-amino acid as a [[post-translational modification]].<ref>{{cite journal | vauthors = Genchi G | title = An overview on D-amino acids | journal = Amino Acids | volume = 49 | issue = 9 | pages = 1521–1533 | date = September 2017 | pmid = 28681245 | doi = 10.1007/s00726-017-2459-5 | s2cid = 254088816 }}</ref>{{efn|The <small>L</small> and <small>D</small> convention for amino acid configuration refers not to the optical activity of the amino acid itself but rather to the optical activity of the isomer of [[glyceraldehyde]] from which that amino acid can, in theory, be synthesized (<small>D</small>-glyceraldehyde is dextrorotatory; <small>L</small>-glyceraldehyde is levorotatory).

An alternative convention is to use the [[Cahn–Ingold–Prelog priority rules|(''S'') and (''R'') designators]] to specify the ''absolute configuration''.<ref name=Cahn>{{Cite journal | vauthors = Cahn RS, Ingold C, Prelog V | author-link = Robert Sidney Cahn | author2-link = Christopher Kelk Ingold | author3-link = Vladimir Prelog | title = Specification of Molecular Chirality | journal = [[Angewandte Chemie International Edition]] | volume = 5 | issue = 4 | pages = 385–415 | year = 1966 | doi = 10.1002/anie.196603851}}</ref> Almost all of the amino acids in proteins are (''S'') at the α carbon, with [[cysteine]] being (''R'') and glycine non-[[Chirality (chemistry)|chiral]].<ref>{{cite web | vauthors = Hatem SM | year = 2006 | url = http://geb.uni-giessen.de/geb/volltexte/2006/3038/index.html | title = Gas chromatographic determination of Amino Acid Enantiomers in tobacco and bottled wines | publisher = University of Giessen | access-date = 17 November 2008 | archive-url = https://web.archive.org/web/20090122104055/http://geb.uni-giessen.de/geb/volltexte/2006/3038/index.html | archive-date = 22 January 2009 | url-status = dead }}</ref> Cysteine has its side chain in the same geometric location as the other amino acids, but the ''R''/''S'' terminology is reversed because [[sulfur]] has higher atomic number compared to the carboxyl oxygen which gives the side chain a higher priority by the [[Cahn–Ingold–Prelog priority rules|Cahn-Ingold-Prelog sequence rules]].}}

===Side chains===

==== Polar charged side chains ====

Five amino acids possess a charge at neutral pH. Often these side chains appear at the surfaces on proteins to enable their solubility in water, and side chains with opposite charges form important electrostatic contacts called [[Salt bridge (protein and supramolecular)|salt bridges]] that maintain structures within a single protein or between interfacing proteins.<ref name="Garrett-2010">{{Cite book | vauthors = Garrett RH, Grisham CM |title=Biochemistry  |date=2010 |publisher=Brooks/Cole, Cengage Learning |isbn=978-0-495-10935-8 |edition=4th |location=Belmont, CA |pages=74,134–176,430–442 |oclc=297392560}}</ref> Many proteins bind metal into their structures specifically, and these interactions are commonly mediated by charged side chains such as [[aspartate]], [[glutamate]] and [[histidine]]. Under certain conditions, each ion-forming group can be charged, forming double salts.<ref>{{Cite journal | vauthors = Novikov AP, Safonov AV, German KE, Grigoriev MS |date=2023-12-01 |title=What kind of interactions we may get moving from zwitter to "dritter" ions: C–O⋯Re(O<sub>4</sub>) and Re–O⋯Re(O<sub>4</sub>) anion⋯anion interactions make structural difference between <small>L</small>-histidinium perrhenate and pertechnetate |journal=CrystEngComm |volume=26 |pages=61–69 |language=en |doi=10.1039/D3CE01164J |s2cid=265572280 |issn=1466-8033}}</ref>

The two negatively charged amino acids at neutral pH are [[Aspartic acid|aspartate]] (Asp, D) and [[Glutamic acid|glutamate]] (Glu, E). The anionic carboxylate groups behave as [[Brønsted–Lowry acid–base theory|Brønsted bases]] in most circumstances.<ref name="Garrett-2010" /> Enzymes in very low pH environments, like the aspartic protease [[pepsin]] in mammalian stomachs, may have catalytic aspartate or glutamate residues that act as Brønsted acids.

[[File:Histidine lysine arginine sidechains.png|class=skin-invert-image|thumb|upright=2.05 |Functional groups found in histidine (left), lysine (middle) and arginine (right)]]

There are three amino acids with side chains that are cations at neutral pH: [[arginine]] (Arg, R), [[lysine]] (Lys, K) and [[histidine]] (His, H). Arginine has a charged [[Guanidine|guanidino]] group and lysine a charged alkyl amino group, and are fully protonated at pH 7. Histidine's imidazole group has a pK<sub>a</sub> of 6.0, and is only around 10% protonated at neutral pH. Because histidine is easily found in its basic and conjugate acid forms it often participates in catalytic proton transfers in enzyme reactions.<ref name="Garrett-2010" />

==== Polar uncharged side chains ====

The polar, uncharged amino acids [[serine]] (Ser, S), [[threonine]] (Thr, T), [[asparagine]] (Asn, N) and [[glutamine]] (Gln, Q) readily form hydrogen bonds with water and other amino acids.<ref name="Garrett-2010" /> They do not ionize in normal conditions, a prominent exception being the catalytic serine in [[Serine protease#Catalytic mechanism|serine proteases]]. This is an example of severe perturbation, and is not characteristic of serine residues in general. Threonine has two chiral centers, not only the <small>L</small> (2''S'') chiral center at the α-carbon shared by all amino acids apart from achiral glycine, but also (3''R'') at the β-carbon. The full [[stereochemical]] specification is (2''S'',3''R'')-<small>L</small>-[[threonine]].

==== Hydrophobic side chains ====

Nonpolar amino acid interactions are the primary driving force behind the processes that [[Protein folding|fold proteins]] into their functional three dimensional structures.<ref name="Garrett-2010" /> None of these amino acids' side chains ionize easily, and therefore do not have pK<sub>a</sub>s, with the exception of [[tyrosine]] (Tyr, Y). The hydroxyl of tyrosine can deprotonate at high pH forming the negatively charged phenolate. Because of this one could place tyrosine into the polar, uncharged amino acid category, but its very low solubility in water matches the characteristics of hydrophobic amino acids well.

==== Special case side chains ====

Several side chains are not described well by the charged, polar and hydrophobic categories. [[Glycine]] (Gly, G) could be considered a polar amino acid since its small size means that its solubility is largely determined by the amino and carboxylate groups. However, the lack of any side chain provides glycine with a unique flexibility among amino acids with large ramifications to protein folding.<ref name="Garrett-2010" /> [[Cysteine]] (Cys, C) can also form hydrogen bonds readily, which would place it in the polar amino acid category, though it can often be found in protein structures forming covalent bonds, called [[disulphide bonds]], with other cysteines. These bonds influence the folding and stability of proteins, and are essential in the formation of [[Antibody#Structure|antibodies]]. [[Proline]] (Pro, P) has an alkyl side chain and could be considered hydrophobic, but because the side chain joins back onto the alpha amino group it becomes particularly inflexible when incorporated into proteins. Similar to glycine this influences protein structure in a way unique among amino acids. [[Selenocysteine]] (Sec, U) is a rare amino acid not directly encoded by DNA, but is incorporated into proteins via the ribosome. Selenocysteine has a lower redox potential compared to the similar cysteine, and participates in several unique enzymatic reactions.<ref>{{cite journal | vauthors = Papp LV, Lu J, Holmgren A, Khanna KK | title = From selenium to selenoproteins: synthesis, identity, and their role in human health | journal = Antioxidants & Redox Signaling | volume = 9 | issue = 7 | pages = 775–806 | date = July 2007 | pmid = 17508906 | doi = 10.1089/ars.2007.1528 }}</ref> [[Pyrrolysine]] (Pyl, O) is another amino acid not encoded in DNA, but synthesized into protein by ribosomes.<ref>{{cite journal | vauthors = Hao B, Gong W, Ferguson TK, James CM, Krzycki JA, Chan MK | title = A new UAG-encoded residue in the structure of a methanogen methyltransferase | journal = Science | volume = 296 | issue = 5572 | pages = 1462–1466 | date = May 2002 | pmid = 12029132 | doi = 10.1126/science.1069556 | s2cid = 35519996 | bibcode = 2002Sci...296.1462H }}</ref> It is found in archaeal species where it participates in the catalytic activity of several methyltransferases.

==== β- and γ-amino acids ====
Amino acids with the structure {{chem2|NH3+\sCXY\sCXY\sCO2-}}, such as [[β-alanine]], a component of [[carnosine]] and a few other peptides, are β-amino acids. Ones with the structure {{chem2|NH3+\sCXY\sCXY\sCXY\sCO2-}} are γ-amino acids, and so on, where X and Y are two substituents (one of which is normally H).<ref name = iupaciub />

===Zwitterions===
<!--[[File:Amino acid zwitterions.svg|thumb|right|An amino acid in its (1) molecular and (2) zwitterionic forms]]-->
{{main|Zwitterion}}

[[File:Bronsted_character_of_ionizing_groups_in_proteins.png|class=skin-invert-image|thumb|upright=1.5|Ionization and Brønsted character of N-terminal amino, C-terminal carboxylate, and side chains of amino acid residues]]
The common natural forms of amino acids have a [[zwitterionic]] structure, with {{chem2|\sNH3+}} ({{chem2|\sNH2+\s}} in the case of proline) and {{chem2|\sCO2-}} functional groups attached to the same C atom, and are thus α-amino acids, and are the only ones found in proteins during translation in the ribosome.
In aqueous solution at pH close to neutrality, amino acids exist as [[zwitterion]]s, i.e. as dipolar ions with both {{chem2|NH3+}} and {{chem2|CO2-}} in charged states, so the overall structure is {{chem2|NH3+\sCHR\sCO2-}}. At [[Acid–base homeostasis|physiological pH]] the so-called "neutral forms" {{chem2|\sNH2\sCHR\sCO2H}} are not present to any measurable degree.<ref>{{cite book | vauthors = Steinhardt J, Reynolds JA |title=Multiple equilibria in proteins |publisher=Academic Press |place=New York |isbn=978-0126654509| pages=176–21 |date=1969}}</ref> Although the two charges in the zwitterion structure add up to zero it is misleading to call a species with a net charge of zero "uncharged".

In strongly acidic conditions (pH below 3), the carboxylate group becomes protonated and the structure becomes an ammonio carboxylic acid, {{chem2|NH3+\sCHR\sCO2H}}. This is relevant for enzymes like pepsin that are active in acidic environments such as the mammalian stomach and [[lysosomes]], but does not significantly apply to intracellular enzymes. In highly basic conditions (pH greater than 10, not normally seen in physiological conditions), the ammonio group is deprotonated to give {{chem2|NH2\sCHR\sCO2-}}.

Although various definitions of acids and bases are used in chemistry, the only one that is useful for chemistry in aqueous solution is [[Brønsted–Lowry acid–base theory|that of Brønsted]]:<ref>{{cite journal | vauthors = Brønsted JN | journal = Recueil des Travaux Chimiques des Pays-Bas | volume = 42 | pages = 718–728 |year= 1923| title = Einige Bemerkungen über den Begriff der Säuren und Basen| issue= 8 | doi= 10.1002/recl.19230420815 |trans-title = Remarks on the concept of acids and bases}}</ref><ref name="Vollhardt-2007" /> an acid is a species that can donate a proton to another species, and a base is one that can accept a proton. This criterion is used to label the groups in the above illustration. The carboxylate side chains of aspartate and glutamate residues are the principal Brønsted bases in proteins. Likewise, lysine, tyrosine and cysteine will typically act as a Brønsted acid. Histidine under these conditions can act both as a Brønsted acid and a base.

===Isoelectric point===
[[File:Titration Curves of 20 Amino Acids Organized by Side Chain.png|class=skin-invert-image|thumb|right|upright=1.5|Composite of [[titration curve]]s of twenty proteinogenic amino acids grouped by side chain category]]

For amino acids with uncharged side-chains the zwitterion predominates at pH values between the two p''K''<sub>a</sub> values, but coexists in [[Chemical equilibrium|equilibrium]] with small amounts of net negative and net positive ions. At the midpoint between the two p''K''<sub>a</sub> values, the trace amount of net negative and trace of net positive ions balance, so that average net charge of all forms present is zero.<ref>{{cite book | vauthors = Fennema OR |title=Food Chemistry 3rd Ed |publisher=CRC Press |pages=327–328 |isbn=978-0-8247-9691-4 |date=1996-06-19 }}</ref> This pH is known as the [[isoelectric point]] p''I'', so p''I'' = {{sfrac|1|2}}(p''K''<sub>a1</sub> + p''K''<sub>a2</sub>).

For amino acids with charged side chains, the p''K''<sub>a</sub> of the side chain is involved. Thus for aspartate or glutamate with negative side chains, the terminal amino group is essentially entirely in the charged form {{chem2|\sNH3+}}, but this positive charge needs to be balanced by the state with just one C-terminal carboxylate group is negatively charged. This occurs halfway between the two carboxylate p''K''<sub>a</sub> values: p''I'' = {{sfrac|1|2}}(p''K''<sub>a1</sub> + p''K''<sub>a(R)</sub>), where p''K''<sub>a(R)</sub> is the side chain p''K''<sub>a</sub>.<ref name="Vollhardt-2007">{{Cite book | vauthors = Vollhardt KP |title=Organic chemistry : structure and function |date=2007 |publisher=W.H. Freeman |others=Neil Eric Schore |isbn=978-0-7167-9949-8 |edition=5th |location=New York |pages=58–66 |oclc=61448218}}</ref>

Similar considerations apply to other amino acids with ionizable side-chains, including not only glutamate (similar to aspartate), but also cysteine, histidine, lysine, tyrosine and arginine with positive side chains.

Amino acids have zero mobility in [[electrophoresis]] at their isoelectric point, although this behaviour is more usually exploited for peptides and proteins than single amino acids. Zwitterions have minimum solubility at their isoelectric point, and some amino acids (in particular, with nonpolar side chains) can be isolated by precipitation from water by adjusting the pH to the required isoelectric point.