Editing Proline

{{Other uses}}
{{Distinguish|Prolene}}
{{Chembox
| ImageFileL2 = Prolin - Proline.svg
| ImageNameL2 = Structural formula of proline
| ImageClassL2 = skin-invert-image
| ImageFileR2 = L-Proline.svg
| ImageCaption = [[skeletal formula]] of proline
| ImageClassR2 = skin-invert-image
| ImageFileL3 = Proline-from-xtal-3D-bs-17-view-B.png
| ImageClassL3 = bg-transparent
| ImageCaptionL3 = [[ball-and-stick model]]
| ImageFileR3 = Proline-from-xtal-3D-sf-view-B.png
| ImageClassR3 = bg-transparent
| ImageCaptionR3 = [[space-filling model]]
| IUPACName = Proline
| SystematicName = Pyrrolidine-2-carboxylic acid<ref>{{cite web| url= https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=614&loc=ec_rcs |title=Proline| work = PubChem |publisher = U.S. National Library of Medicine |access-date=8 May 2018|url-status=live|archive-url=https://web.archive.org/web/20140116114913/http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=614&loc=ec_rcs|archive-date=16 January 2014}}</ref>
|Section1={{Chembox Identifiers
| index1_label = D/L
| index2_label = D
| index_label = L <!-- needs to be L (natural isomer) so drugbank etc. take correct index_label -->
| CASNo1 = 609-36-9
| CASNo1_Ref = {{cascite|correct|CAS}}
| CASNo2 = 344-25-2
| CASNo2_Ref = {{cascite|correct|CAS}}
| CASNo = 147-85-3
| CASNo_Ref = {{cascite|correct|CAS}}
| PubChem1 = 614
| PubChem2 = 8988
| PubChem = 145742
| ChemSpiderID1 = 594
| ChemSpiderID1_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID2 = 8640
| ChemSpiderID2_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 128566
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| UNII1 = DCS9E77JPQ
| UNII1_Ref = {{fdacite|correct|FDA}}
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = L01Q4LGZ5L
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9DLQ4CIU6V
| EINECS = 210-189-3
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00172
| KEGG = C00148
| KEGG_Ref = {{keggcite|correct|kegg}}
| MeSHName = Proline
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17203
| ChEBI1_Ref = {{ebicite|correct|EBI}}
| ChEBI1 = 26271
| ChEBI2_Ref = {{ebicite|correct|EBI}}
| ChEBI2 = 16313
| ChEMBL = 72275
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| RTECS = TW3584000
| Beilstein = 80812
| Gmelin = 26927
| SMILES = C1C[C@H](NC1)C(=O)O
| SMILES3 = [O-]C(=O)[C@H](CCC2)[NH2+]2
| SMILES3_Comment = L [[Zwitterion]]
| StdInChI = 1S/C5H9NO2/c7-5(8)4-2-1-3-6-4/h4,6H,1-3H2,(H,7,8)/t4-/m0/s1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ONIBWKKTOPOVIA-BYPYZUCNSA-N
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| InChIKey1 = ONIBWKKTOPOVIA-UHFFFAOYSA-N
| InChIKey2 = ONIBWKKTOPOVIA-SCSAIBSYSA-N
}}
|Section2={{Chembox Properties
| C = 5
| H = 9
| N = 1
| O = 2
| Appearance = Transparent crystals
| MeltingPtC = 205 to 228
| MeltingPt_notes = (decomposes)
| LogP = −0.06
| pKa=1.99 (carboxyl), 10.96 (amino)<ref>{{cite book | vauthors = Nelson DL, Cox MM | title = Principles of Biochemistry | location = New York | publisher = W.H. Freeman and Company }}</ref>
| SolubleOther = 1.5g/100g ethanol 19 degC<ref>{{cite book |title=Food Chemistry | vauthors = Belitz HD, Grosch W, Schieberle P |isbn= 978-3-540-69933-0 |page=15 |url=https://books.google.com/books?id=xteiARU46SQC&q=proline&pg=PA15 |url-status=live |archive-url=https://web.archive.org/web/20160515000801/https://books.google.com/books?id=xteiARU46SQC&pg=PA15&lpg=PA15&dq=proline&redir_esc=y#v=onepage&q=proline&f=false |archive-date=2016-05-15 |date=2009-01-15 | publisher = Springer }}
</ref>
}}
|Section3={{Chembox Hazards
}}
}}
[[File:Proline-spin.gif|thumb|Proline ball and stick model spinning]]
'''Proline''' (symbol '''Pro''' or '''P''')<ref>{{cite web| url = http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html | title = Nomenclature and Symbolism for Amino Acids and Peptides | publisher = IUPAC-IUB Joint Commission on Biochemical Nomenclature | year = 1983 | access-date = 5 March 2018| archive-url= https://web.archive.org/web/20081009023202/http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html| archive-date= 9 October 2008 | url-status= dead}}</ref> is an organic acid classed as a [[proteinogenic amino acid]] (used in the [[Protein biosynthesis|biosynthesis of proteins]]), although it does not contain the [[amino group]] {{chem|-NH|2}} but is rather a [[secondary amine]]. The secondary amine nitrogen is in the protonated form (NH<sub>2</sub><sup>+</sup>) under biological conditions, while the [[carboxyl group]] is in the [[deprotonated]] −COO<sup>−</sup> form. The "side chain" from the [[Alpha and beta carbon|α carbon]] connects to the nitrogen forming a [[pyrrolidine]] loop, classifying it as a [[aliphatic]] [[amino acid]]. It is non-essential in humans, meaning the body can synthesize it from the non-essential amino acid <small>L</small>-[[glutamate]]. It is [[Genetic code|encoded]] by all the [[codon]]s starting with CC (CCU, CCC, CCA, and CCG).

Proline is the only proteinogenic [[secondary amino acid|amino acid which is a secondary amine]], as the nitrogen atom is attached both to the α-carbon and to a chain of three carbons that together form a five-membered ring.

==History and etymology==
Proline was first isolated in 1900 by [[Richard Willstätter]] who obtained the amino acid while studying ''N''-methylproline, and synthesized proline by the reaction of sodium salt of [[diethyl malonate]] with [[1,3-dibromopropane]]. The next year, [[Emil Fischer]] isolated proline from [[casein]] and the decomposition products of γ-phthalimido-propylmalonic ester,<ref>{{Citation | vauthors = Plimmer RH |author-link=R. H. A. Plimmer | veditors = Plimmer RH, Hopkins FG |title= The chemical composition of the proteins |url= https://books.google.com/books?id=7JM8AAAAIAAJ&pg=PA130 |access-date= September 20, 2010 |edition= 2nd |series= Monographs on biochemistry |volume= Part I. Analysis |orig-year= 1908 |year= 1912 |publisher= Longmans, Green and Co. |location= London|page= 130}}</ref> and published the synthesis of proline from phthalimide propylmalonic ester.<ref>{{cite web|title=Proline|url=http://www.aminoacidsguide.com/Pro.html|url-status=live|archive-url=https://web.archive.org/web/20151127055301/http://www.aminoacidsguide.com/Pro.html|archive-date=2015-11-27 | work = Amino Acids Guide }}</ref>

The name proline comes from [[pyrrolidine]], one of its constituents.<ref>{{cite web |url=http://www.yourdictionary.com/proline |title=Proline |work=American Heritage Dictionary of the English Language, 4th edition |access-date=2015-12-06 |url-status=live |archive-url=https://web.archive.org/web/20150915121147/http://www.yourdictionary.com/proline |archive-date=2015-09-15 }}</ref>

== Biosynthesis ==
Proline is [[Biosynthesis|biosynthetically]] derived from the amino acid <small>L</small>-[[glutamate]].  [[Glutamate-5-semialdehyde]] is first formed by [[glutamate 5-kinase]] (ATP-dependent) and [[glutamate-5-semialdehyde dehydrogenase]] (which requires NADH or NADPH). This can then either spontaneously cyclize to form [[1-pyrroline-5-carboxylic acid]], which is reduced to proline by [[pyrroline-5-carboxylate reductase]] (using NADH or NADPH), or turned into [[ornithine]] by [[ornithine aminotransferase]], followed by cyclisation by [[ornithine cyclodeaminase]] to form proline.<ref>{{Lehninger3rd|name-list-style=vanc}}.</ref>

[[File:Betain-Proline.png|thumb|left|260px|[[Zwitterion]]ic structure of both proline enantiomers: (''S'')-proline (left) and (''R'')-proline]]

==Biological activity==
<small>L</small>-Proline has been found to act as a weak [[agonist]] of the [[glycine receptor]] and of both [[NMDA receptor|NMDA]] and non-NMDA ([[AMPA receptor|AMPA]]/[[kainate receptor|kainate]]) [[ionotropic glutamate receptor]]s.<ref name="AcademicPress1995">{{cite book|title=Ion Channel Factsbook: Extracellular Ligand-Gated Channels|url=https://books.google.com/books?id=XqzdupxdZUgC&pg=PA126|date=16 November 1995|publisher=Academic Press|isbn=978-0-08-053519-7|pages=126|url-status=live|archive-url=https://web.archive.org/web/20160426213947/https://books.google.com/books?id=XqzdupxdZUgC&pg=PA126|archive-date=26 April 2016}}</ref><ref name="pmid1349155">{{cite journal | vauthors = Henzi V, Reichling DB, Helm SW, MacDermott AB | title = L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons | journal = Molecular Pharmacology | volume = 41 | issue = 4 | pages = 793–801 | date = April 1992 | doi = 10.1016/S0026-895X(25)09065-0 | pmid = 1349155 | url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1349155 | archive-url = https://archive.today/20150115015124/http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1349155 | url-status = dead | archive-date = January 15, 2015 | url-access = subscription }}</ref><ref name="Arslan2014">{{cite book| vauthors = Arslan OE |title=Neuroanatomical Basis of Clinical Neurology | edition = Second |url=https://books.google.com/books?id=UTv6AwAAQBAJ&pg=PA309|date=7 August 2014|publisher=CRC Press|isbn=978-1-4398-4833-3|pages=309|url-status=live|archive-url=https://web.archive.org/web/20160514155908/https://books.google.com/books?id=UTv6AwAAQBAJ&pg=PA309|archive-date=14 May 2016}}</ref> It has been proposed to be a potential [[endogenous]] [[excitotoxin]].<ref name="AcademicPress1995" /><ref name="pmid1349155" /><ref name="Arslan2014" /> In [[plants]], proline accumulation is a common physiological response to various stresses but is also part of the developmental program in [[generative tissues]] (e.g. [[pollen]]).<ref name="pmid18379856">{{cite journal | vauthors = Verbruggen N, Hermans C | title = Proline accumulation in plants: a review | journal = Amino Acids | volume = 35 | issue = 4 | pages = 753–759 | date = November 2008 | pmid = 18379856 | doi = 10.1007/s00726-008-0061-6 | s2cid = 21788988 | url = https://dipot.ulb.ac.be/dspace/bitstream/2013/57922/4/Verbruggen_and_Hermans_2008_Amino_Acids.pdf }}</ref><ref>{{cite journal | vauthors = Shrestha A, Fendel A, Nguyen TH, Adebabay A, Kullik AS, Benndorf J, Leon J, Naz AA | display-authors = 6 | title = Natural diversity uncovers P5CS1 regulation and its role in drought stress tolerance and yield sustainability in barley | journal = Plant, Cell & Environment | pages = 3523–3536 | date = September 2022 | volume = 45 | issue = 12 | pmid = 36130879 | doi = 10.1111/pce.14445 | s2cid = 252438394 | doi-access = free | bibcode = 2022PCEnv..45.3523S }}</ref><ref>{{cite journal | vauthors = Shrestha A, Cudjoe DK, Kamruzzaman M, Siddique S, Fiorani F, Léon J, Naz AA | title = Abscisic acid-responsive element binding transcription factors contribute to proline synthesis and stress adaptation in Arabidopsis | journal = Journal of Plant Physiology | volume = 261 | pages = 153414 | date = June 2021 | pmid = 33895677 | doi = 10.1016/j.jplph.2021.153414 | bibcode = 2021JPPhy.26153414S | s2cid = 233397785 }}</ref><ref>{{cite journal | vauthors = Muzammil S, Shrestha A, Dadshani S, Pillen K, Siddique S, Léon J, Naz AA | title = An Ancestral Allele of ''Pyrroline-5-carboxylate synthase1'' Promotes Proline Accumulation and Drought Adaptation in Cultivated Barley | journal = Plant Physiology | volume = 178 | issue = 2 | pages = 771–782 | date = October 2018 | pmid = 30131422 | pmc = 6181029 | doi = 10.1104/pp.18.00169 }}</ref>

A diet rich in proline was linked to an increased risk of depression in humans in a study from 2022 that was tested on a limited pre-clinical trial on humans and primarily in other organisms. Results were significant in the other organisms.<ref name="pmid35508109">{{cite journal | vauthors = Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, Martin M, de la Vega-Correa L, Zapata C, Burokas A, Blasco G, Coll C, Escrichs A, Biarnés C, Moreno-Navarrete JM, Puig J, Garre-Olmo J, Ramos R, Pedraza S, Brugada R, Vilanova JC, Serena J, Gich J, Ramió-Torrentà L, Pérez-Brocal V, Moya A, Pamplona R, Sol J, Jové M, Ricart W, Portero-Otin M, Deco G, Maldonado R, Fernández-Real JM | display-authors = 6 | title = Microbiota alterations in proline metabolism impact depression | journal = Cell Metabolism | volume = 34 | issue = 5 | pages = 681–701.e10 | date = May 2022 | pmid = 35508109 | doi = 10.1016/j.cmet.2022.04.001 | s2cid = 248528026 | hdl = 10230/53513 | doi-access = free | hdl-access = free }}</ref>

==Properties in protein structure==
The distinctive cyclic structure of proline's side chain gives proline an exceptional conformational rigidity compared to other amino acids.  It also affects the rate of peptide bond formation between proline and other amino acids.  When proline is bound as an amide in a peptide bond, its nitrogen is not bound to any hydrogen, meaning it cannot act as a [[hydrogen bond]] donor, but can be a hydrogen bond acceptor.

Peptide bond formation with incoming Pro-tRNA<sup>Pro</sup> in the ribosome is considerably slower than with any other tRNAs, which is a general feature of ''N''-alkylamino acids.<ref>{{cite journal | vauthors = Pavlov MY, Watts RE, Tan Z, Cornish VW, Ehrenberg M, Forster AC | title = Slow peptide bond formation by proline and other ''N''-alkylamino acids in translation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 1 | pages = 50–54 | date = January 2009 | pmid = 19104062 | pmc = 2629218 | doi = 10.1073/pnas.0809211106 | bibcode = 2009PNAS..106...50P | doi-access = free }}.</ref>  Peptide bond formation is also slow between an incoming tRNA and a chain ending in proline; with the creation of proline-proline bonds slowest of all.<ref>{{cite journal | vauthors = Buskirk AR, Green R | title = Biochemistry. Getting past polyproline pauses | journal = Science | volume = 339 | issue = 6115 | pages = 38–39 | date = January 2013 | pmid = 23288527 | pmc = 3955122 | doi = 10.1126/science.1233338 | bibcode = 2013Sci...339...38B }}</ref>

The exceptional conformational rigidity of proline affects the [[secondary structure]] of proteins near a proline residue and may account for proline's higher prevalence in the proteins of [[thermophile|thermophilic]] organisms.  [[Protein secondary structure]] can be described in terms of the [[dihedral angle]]s [[Dihedral angle#Dihedral angles of biological molecules|φ, ψ and ω]] of the protein backbone.  The cyclic structure of proline's side chain locks the angle φ at approximately −65°.<ref>{{cite journal | vauthors = Morris AL, MacArthur MW, Hutchinson EG, Thornton JM | title = Stereochemical quality of protein structure coordinates | journal = Proteins | volume = 12 | issue = 4 | pages = 345–364 | date = April 1992 | pmid = 1579569 | doi = 10.1002/prot.340120407 | s2cid = 940786 }}</ref>

Proline acts as a structural disruptor in the middle of regular [[secondary structure]] elements such as [[alpha helix|alpha helices]] and [[beta sheet]]s; however, proline is commonly found as the first residue of an [[alpha helix]] and also in the edge strands of [[beta sheet]]s.  Proline is also commonly found in [[turn (biochemistry)|turns]] (another kind of secondary structure), and aids in the formation of beta turns.  This may account for the curious fact that proline is usually solvent-exposed, despite having a completely [[aliphatic]] side chain.

Multiple prolines and/or [[hydroxyproline]]s in a row can create a [[polyproline helix]], the predominant [[secondary structure]] in [[collagen]]. The [[hydroxylation]] of proline by [[prolyl hydroxylase]] (or other additions of electron-withdrawing substituents such as [[fluorine]]) increases the conformational stability of [[collagen]] significantly.<ref name="SzpakJAS">{{Cite journal | vauthors = Szpak P  |title=Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis |url=https://uwo.academia.edu/PaulSzpak/Papers/827788/Fish_Bone_Chemistry_and_Ultrastructure_Implications_for_Taphonomy_and_Stable_Isotope_Analysis |journal=[[Journal of Archaeological Science]] |year=2011 |volume=38 |issue=12 |pages=3358–3372 |doi=10.1016/j.jas.2011.07.022 |bibcode=2011JArSc..38.3358S |url-status=live |archive-url=https://web.archive.org/web/20120118065911/http://uwo.academia.edu/PaulSzpak/Papers/827788/Fish_Bone_Chemistry_and_Ultrastructure_Implications_for_Taphonomy_and_Stable_Isotope_Analysis |archive-date=2012-01-18 }}</ref>  Hence, the hydroxylation of proline is a critical biochemical process for maintaining the [[connective tissue]] of higher organisms.  Severe diseases such as [[scurvy]] can result from defects in this hydroxylation, e.g., mutations in the enzyme prolyl hydroxylase or lack of the necessary [[vitamin C|ascorbate (vitamin C)]] cofactor.

==''Cis''–''trans'' isomerization==
[[Peptide bond]]s to proline, and to other ''N''-substituted amino acids (such as [[sarcosine]]), are able to populate both the ''[[Cis-trans isomerism|cis]]'' and ''[[trans isomer|trans]]'' isomers.  Most peptide bonds overwhelmingly adopt the ''trans'' isomer (typically 99.9% under unstrained conditions), chiefly because the amide hydrogen (''trans'' isomer) offers less steric repulsion to the preceding C<sub>α</sub> atom than does the following C<sub>α</sub> atom (''cis'' isomer).  By contrast, the ''cis'' and ''trans'' isomers of the X-Pro peptide bond (where X represents any amino acid) both experience steric clashes with the neighboring substitution and have a much lower energy difference.  Hence, the fraction of X-Pro peptide bonds in the ''cis'' isomer under unstrained conditions is significantly elevated, with ''cis'' fractions typically in the range of 3-10%.<ref name="alderson">{{cite journal | vauthors = Alderson TR, Lee JH, Charlier C, Ying J, Bax A | title = Propensity for ''cis''-Proline Formation in Unfolded Proteins | journal = ChemBioChem | volume = 19 | issue = 1 | pages = 37–42 | date = January 2018 | pmid = 29064600 | pmc = 5977977 | doi = 10.1002/cbic.201700548 | name-list-style = amp }}</ref> However, these values depend on the preceding amino acid, with Gly<ref name="sarkar">{{cite journal | vauthors = Sarkar SK, Young PE, Sullivan CE, Torchia DA | title = Detection of ''cis'' and ''trans'' X–Pro peptide bonds in proteins by 13C NMR: application to collagen | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 15 | pages = 4800–4803 | date = August 1984 | pmid = 6589627 | pmc = 391578 | doi = 10.1073/pnas.81.15.4800 | name-list-style = amp | doi-access = free | bibcode = 1984PNAS...81.4800S }}</ref> and aromatic<ref name="thomas">{{cite journal | vauthors = Thomas KM, Naduthambi D, Zondlo NJ | title = Electronic control of amide ''cis''–''trans'' isomerism via the aromatic-prolyl interaction | journal = Journal of the American Chemical Society | volume = 128 | issue = 7 | pages = 2216–2217 | date = February 2006 | pmid = 16478167 | doi = 10.1021/ja057901y | name-list-style = amp }}</ref> residues yielding increased fractions of the ''cis'' isomer. ''Cis'' fractions up to 40% have been identified for aromatic–proline peptide bonds.<ref name="gustafson">{{cite journal | vauthors = Gustafson CL, Parsley NC, Asimgil H, Lee HW, Ahlbach C, Michael AK, Xu H, Williams OL, Davis TL, Liu AC, Partch CL | display-authors = 6 | title = A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates Circadian Rhythms | journal = Molecular Cell | volume = 66 | issue = 4 | pages = 447–457.e7 | date = May 2017 | pmid = 28506462 | pmc = 5484534 | doi = 10.1016/j.molcel.2017.04.011 | name-list-style = amp }}</ref>

From a kinetic standpoint, ''cis''–''trans'' proline [[isomerization]] is a very slow process that can impede the progress of [[protein folding]] by trapping one or more proline residues crucial for folding in the non-native isomer, especially when the native protein requires the ''cis'' isomer.  This is because proline residues are exclusively synthesized in the [[ribosome]] as the ''trans'' isomer form. All organisms possess [[prolyl isomerase]] [[enzyme]]s to catalyze this isomerization, and some [[bacteria]] have specialized prolyl isomerases associated with the ribosome.  However, not all prolines are essential for folding, and protein folding may proceed at a normal rate despite having non-native conformers of many X–Pro peptide bonds.

==Uses==
Proline and its derivatives are often used as asymmetric catalysts in [[proline organocatalysis]] reactions. The [[CBS reduction]] and proline catalysed [[aldol condensation]] are prominent examples.

In brewing, proteins rich in proline combine with polyphenols to produce haze (turbidity).<ref>{{cite web | vauthors = Siebert KJ | title = Haze and Foam | url= http://www.nysaes.cornell.edu/fst/faculty/siebert/haze.html |website=Cornell AgriTech |access-date=2010-07-13 |url-status=live |archive-url=https://web.archive.org/web/20100711180909/http://www.nysaes.cornell.edu/fst/faculty/siebert/haze.html |archive-date=2010-07-11 }} Accessed July 12, 2010.</ref>

<small>L</small>-Proline is an [[osmoprotectant]] and therefore is used in many pharmaceutical and biotechnological applications.

The [[growth medium]] used in [[plant tissue culture]] may be supplemented with proline.  This can increase growth, perhaps because it helps the plant tolerate the stresses of tissue culture.<ref name="pazuki">{{cite journal | vauthors = Pazuki A, Asghari J, Sohani MM, Pessarakli M, Aflaki F |year=2015 |title= Effects of Some Organic Nitrogen Sources and Antibiotics on Callus Growth of Indica Rice Cultivars |journal= Journal of Plant Nutrition |volume=38 |issue=8 |pages=1231–1240 |doi=10.1080/01904167.2014.983118 |bibcode=2015JPlaN..38.1231P |s2cid=84495391 }}</ref>{{Better source needed|reason=Source is a primary study, claiming supplementation improves rice growth.  We want a review or book that shows proline supplementation is ''often'' used to culture a ''variety'' of plants.|date=June 2016}}  For proline's role in the stress response of plants, see {{slink||Biological activity}}.

==Specialties==
Proline is one of the two amino acids that do not follow along with the typical [[Ramachandran plot]], along with [[glycine]]. Due to the ring formation connected to the beta carbon, the ''ψ'' and ''φ'' angles about the peptide bond have fewer allowable degrees of rotation. As a result, it is often found in "turns" of proteins as its free entropy (Δ''S'') is not as comparatively large to other amino acids and thus in a folded form vs. unfolded form, the change in entropy is smaller. Furthermore, proline is rarely found in α and β structures as it would reduce the stability of such structures, because its side chain α-nitrogen can only form one nitrogen bond.

Additionally, proline is the only amino acid that does not form a red-purple colour when developed by spraying with [[ninhydrin]] for uses in [[chromatography]]. Proline, instead, produces an orange-yellow colour.

==Synthesis==
[[Racemic]] proline can be synthesized from [[diethyl malonate]] and [[acrylonitrile]]:<ref>Vogel, ''Practical Organic Chemistry'' 5th edition</ref>
:[[File:DL-Proline synth.png|500px|class=skin-invert-image]]{{clear left}}

== See also ==
* [[Hyperprolinemia]]
* [[Inborn error of metabolism]]
* [[Prolidase deficiency]]
* [[Prolinol]]

== References ==
{{Reflist|30em}}

== Further reading ==
{{refbegin}}
* {{cite book | vauthors = Balbach J, Schmid FX | year = 2000 | contribution = Proline isomerization and its catalysis in protein folding | title = Mechanisms of Protein Folding | edition = 2nd | veditors = Pain RH | publisher = Oxford University Press | pages = 212–249 | isbn = 978-0-19-963788-1}}.
{{refend}}

== External links ==
* [http://gmd.mpimp-golm.mpg.de/Spectrums/421929e5-2ddf-45bc-a7a3-533eeee502a6.aspx Proline MS Spectrum]
* [https://web.archive.org/web/20110722050400/http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/Pro.html Proline biosynthesis]
* [http://www.biocarta.com/pathfiles/prolinePathway.asp Proline biosynthesis]

{{Amino acids}}
{{Amino acid metabolism intermediates}}
{{Ionotropic glutamate receptor modulators}}
{{Glycine receptor modulators}}
{{Authority control}}

[[Category:Alpha-Amino acids]]
[[Category:AMPA receptor agonists]]
[[Category:Kainate receptor agonists]]
[[Category:NMDA receptor agonists]]
[[Category:Proteinogenic amino acids]]
[[Category:Glucogenic amino acids]]
[[Category:Glycine receptor agonists]]
[[Category:Cyclic amino acids]]
[[Category:Pyrrolidines]]
[[Category:Secondary amino acids]]
[[Category:Excitatory amino acids]]