View source for Serine

{{short description|Amino acid}}
{{About||the French wine grape|Sérine|the toxic substance|Sarin}}
{{cs1 config|name-list-style=vanc}}
{{chembox
| Name           = Serine
| ImageFileL1    = L-Serin - L-Serine.svg
| ImageClassL1   = skin-invert-image
| ImageNameL1    = Skeletal formula
| ImageCaptionL1 = [[Skeletal formula]] of <small>L</small>-serine
| ImageFileR1    = Serine at 7.4 pH.png
| ImageClassR1   = skin-invert-image
| ImageNameR1    = Serine at physiological pH
| ImageCaptionR1 = <small>L</small>-serine [[zwitterion]]
| ImageFileL2    = Serine-from-xtal-view-1-3D-bs-17.png
| ImageClassL2   = bg-transparent
| ImageSizeL2    = 115
| ImageCaptionL2 = [[Ball-and-stick model]]
| ImageFileR2    = Serine-from-xtal-view-1-3D-sf.png
| ImageClassR2   = bg-transparent
| ImageSizeR2    = 110
| ImageCaptionR2 = [[Space-filling model]]
| IUPACName      = Serine
| OtherNames     = 
| SystematicName = 2-Amino-3-hydroxypropanoic acid
| Section1       = {{Chembox Identifiers
|index1_label = D/L
|index2_label = D
|index_label = L <!-- needs to be L (natural isomer) so drugbank etc. take correct index_label -->
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 11298
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C3H7NO3/c4-2(1-5)3(6)7/h2,5H,1,4H2,(H,6,7)/t2-/m0/s1
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = MTCFGRXMJLQNBG-REOHCLBHSA-N
|InChIKey1 = MTCFGRXMJLQNBG-UHFFFAOYSA-N
|InChIKey2 = MTCFGRXMJLQNBG-UWTATZPHSA-N
|CASNo_Ref = {{cascite|correct|CAS}}
|CASNo = 56-45-1
|CASNo1_Ref = {{cascite|correct|CAS}}
|CASNo1 = 302-84-1
|CASNo2_Ref = {{cascite|correct|CAS}}
|CASNo2 = 312-84-5
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = 452VLY9402
|UNII1_Ref = {{fdacite|correct|FDA}}
|UNII1 = 00PAR1C66F
|UNII2_Ref = {{fdacite|correct|FDA}}
|UNII2 = 1K77H2Z9B1
|EC_number = 206-130-6
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID = 5736
|ChemSpiderID1_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID1 = 597
|ChemSpiderID2_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID2 =64231
|KEGG = C00065
|KEGG2 = C00740
|PubChem = 5951
|PubChem1 = 617
|PubChem2 = 71077
|IUPHAR_ligand = 726
|DrugBank_Ref = {{drugbankcite|correct|drugbank}}
|DrugBank = DB00133
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI = 17115
|SMILES = C([C@@H](C(=O)O)N)O
|SMILES1 = C([C@@H](C(=O)[O-])[NH3+])O
|SMILES1_Comment = [[Zwitterion]]
}}
| Section2       = {{Chembox Properties
| Properties_ref = <ref>{{cite book | editor-last = Weast | editor-first = Robert C. | title = CRC Handbook of Chemistry and Physics | edition = 62nd | location = Boca Raton, FL | publisher = CRC Press | date = 1981 | isbn = 0-8493-0462-8 |  page = C-512}}</ref>
|C=3 | H=7 | N=1 | O=3
|Appearance = white crystals or powder
|Density = 1.603 g/cm<sup>3</sup> (22&nbsp;°C)
|MeltingPtC = 246
|MeltingPt_notes = decomposes
|Solubility = soluble
|pKa=2.21 (carboxyl), 9.15 (amino)<ref>Dawson, R.M.C., et al., ''Data for Biochemical Research'', Oxford, Clarendon Press, 1959.</ref>
}}
}}
[[File:Serine-spin.gif|thumb|Serine ball and stick model spinning]]
'''Serine'''
{{IPA|en| ˈsɪəriːn }}
(symbol '''Ser''' or '''S''')<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= live}}</ref><ref>{{IUPAC-IUB amino acids 1983}}.</ref> is an α-[[amino acid]] that is used in the biosynthesis of proteins. It contains an α-[[amino group]] (which is in the [[protonated]] −{{chem|N|H|3|+}} form under biological conditions), a [[carboxyl group]] (which is in the [[deprotonated]] −{{chem|C|O|O|-}} form under biological conditions), and a side chain consisting of a [[hydroxymethyl]] group, classifying it as a [[Chemical polarity|polar]] amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the [[codons]] UCU, UCC, UCA, UCG, AGU and AGC.

== Occurrence ==
[[File:Betain-Serin.png|class=skin-invert-image|thumb|left|250px|<small>L</small>-Serine (left) and <small>D</small>-serine (right) in zwitterionic form at neutral pH]]
This compound is one of the [[proteinogenic amino acid]]s. Only the <small>L</small>-[[stereoisomer]] appears naturally in proteins. It is [[non-essential amino acid|not essential]] to the human diet, since it is synthesized in the body from other [[metabolites]], including [[glycine]]. Serine was first obtained from [[silk]] protein, a particularly rich source, in 1865 by Emil Cramer.<ref>{{cite journal |last1=Cramer |first1=Emil |title=Ueber die Bestandtheile der Seide |journal=Journal für praktische Chemie |date=1865 |volume=96 |pages=76–98 |url=https://babel.hathitrust.org/cgi/pt?id=hvd.hxgq72&view=1up&seq=94 |trans-title=On the constituents of silk |language=German}}  Serine is named on p. 93:  ''"Ich werde den in Frage stehenden Körper unter dem Namen Serin beschreiben."'' (I will describe the body [i.e., substance] in question by the name "serine".)</ref> Its name is derived from the [[Latin]] for silk, ''[[wikt:sericum|sericum]]''.  Serine's structure was established in 1902.<ref>{{cite journal |last1=Fischer |first1=Emil |last2=Leuchs |first2=Hermann |title=Synthese des Serins, der ''l''-Glucosaminsäure und anderer Oxyaminosäuren |journal=Berichte der Deutschen Chemischen Gesellschaft |date=1902 |volume=35 |issue=3 |pages=3787–3805 |doi=10.1002/cber.190203503213 |url=https://babel.hathitrust.org/cgi/pt?id=hvd.cl1i27&view=1up&seq=1255 |trans-title=Synthesis of serine, of ''l''-glucosaminic acid, and other oxyamino acids |language=de|url-access=subscription }}</ref><ref>{{cite encyclopedia|title=Serine|url=http://www.encyclopedia.com/topic/serine.aspx|encyclopedia=The Columbia Encyclopedia 6th ed.|publisher=encyclopedia.com|access-date=22 October 2012}}</ref>

== Biosynthesis ==
The biosynthesis of serine starts with the [[oxidation]] of [[3-phosphoglycerate]] (an intermediate from [[glycolysis]]) to [[3-phosphohydroxypyruvate]] and [[NADH]] by [[phosphoglycerate dehydrogenase]] ({{EC number|1.1.1.95}}). [[Reductive amination]] (transamination) of this ketone by [[phosphoserine transaminase]] ({{EC number|2.6.1.52}}) yields [[3-phosphoserine]] (''O''-phosphoserine) which is hydrolyzed to  serine by [[phosphoserine phosphatase]] ({{EC number|3.1.3.3}}).<ref name=Stryer1988>{{cite book | last1 = Stryer | first1 = Lubert | title = Biochemistry | date = 1988 | publisher = W.H. Freeman | location = New York | isbn = 978-0-7167-1843-7 | edition = 3rd | page = [https://archive.org/details/biochemistry3rdedi00stry/page/580 580] | url-access = registration | url = https://archive.org/details/biochemistry3rdedi00stry/page/580 }}</ref><ref>KEGG [http://www.genome.jp/dbget-bin/www_bget?ec:3.1.3.3 EC 3.1.3.3] etc.</ref>

In bacteria such as [[Escherichia coli|''E. coli'']] these enzymes are encoded by the genes serA (EC 1.1.1.95), serC (EC 2.6.1.52), and serB (EC 3.1.3.3).<ref>Uniprot: [https://www.uniprot.org/uniprot/P0AGB0 serB]</ref>
[[File:Serine biosynthesis.svg|class=skin-invert-image|left|thumb|400x400px|Serine biosynthesis]]

[[Serine hydroxymethyltransferase]] (SMHT) also catalyzes the biosynthesis of [[glycine]] (retro-aldol cleavage) from serine, transferring the resulting formaldehyde synthon to [[5,6,7,8-tetrahydrofolate]].  However, that reaction is reversible, and will convert excess glycine to serine.<ref>{{cite book | first1 = Albert L. | last1 = Lehninger | first2 = David L. | last2 = Nelson | first3 = Michael M. | last3 = Cox | title = Principles of Biochemistry | edition = 3rd | publisher = W.&nbsp;H. Freeman | location = New York | year = 2000 | isbn = 1-57259-153-6 | url-access = registration | url = https://archive.org/details/lehningerprincip01lehn }}</ref> SHMT is a [[pyridoxal phosphate]] (PLP) dependent enzyme.<ref name="Stryer1988"/>

==Synthesis and reactions==
Industrially, <small>L</small>-serine is produced from glycine and methanol catalyzed by [[hydroxymethyltransferase]].<ref>{{Ullmann|author=Karlheinz Drauz, Ian Grayson, Axel Kleemann, Hans-Peter Krimmer, Wolfgang Leuchtenberger, Christoph Weckbecker|year=2006|doi=10.1002/14356007.a02_057.pub2}}</ref>

Racemic serine can be prepared in the laboratory from [[methyl acrylate]] in several steps:<ref>{{cite journal | journal =  [[Organic Syntheses|Org. Synth.]] | last1 = Carter | first1 = Herbert E. | author-link1 = H. E. Carter | last2 = West | first2 = Harold D. | author-link2 = Harold Dadford West | title = ''dl''-Serine | url = http://www.orgsyn.org/demo.aspx?prep=cv3p0774 | volume = 20 | page = 81 | year = 1940 | doi=10.15227/orgsyn.020.0081| url-access = subscription }}</ref>
:[[File:Synthesis of dl-serine.svg|class=skin-invert-image|450x450px]]

Hydrogenation of serine gives the diol [[serinol]]:
:{{chem2|HOCH2CH(NH2)CO2H  +  2 H2  →  HOCH2CH(NH2)CH2OH  +  2 H2O}}

== Biological function ==

=== Metabolic ===
[[File:Cysteine biosynthesis.svg|class=skin-invert-image|thumb|150px|Cysteine synthesis from serine. [[Cystathionine beta synthase]] catalyzes the upper reaction and [[cystathionine gamma-lyase]] catalyzes the lower reaction.]]

Serine is important in [[metabolism]] in that it participates in the [[biosynthesis]] of [[purines]] and [[pyrimidines]]. It is the precursor to several amino acids including [[glycine]] and [[cysteine]], as well as [[tryptophan]] in bacteria. It is also the precursor to numerous other metabolites, including [[sphingolipid]]s and [[folate]], which is the principal donor of one-carbon fragments in biosynthesis.{{Citation needed|date=January 2021}}

=== Signaling ===
<small>D</small>-Serine, synthesized in neurons by [[serine racemase]] from <small>L</small>-serine (its [[enantiomer]]), serves as a neuromodulator by coactivating [[NMDA receptor]]s, making them able to open if they then also bind [[glutamate]]. <small>D</small>-serine is a potent [[agonist]] at the [[glycine]] site (NR1) of canonical diheteromeric [[NMDA receptor]]s. For the receptor to open, glutamate and either glycine or <small>D</small>-serine must bind to it; in addition a pore blocker must not be bound (e.g. Mg<sup>2+</sup> or Zn<sup>2+</sup>).<ref>{{cite journal |vauthors=Liu Y, Hill RH, Arhem P, von Euler G |title=NMDA and glycine regulate the affinity of the Mg2+-block site in NR1-1a/NR2A NMDA receptor channels expressed in Xenopus oocytes |journal=Life Sciences |volume=68 |issue=16 |pages=1817–1826 |year=2001 |pmid=11292060 |doi=10.1016/S0024-3205(01)00975-4 }}</ref> Some research has shown that <small>D</small>-serine is a more potent agonist at the NMDAR glycine site than glycine itself.<ref name="MacKay 2019">{{cite journal | last1=MacKay | first1=Mary-Anne B. | last2=Kravtsenyuk | first2=Maryana | last3=Thomas | first3=Rejish | last4=Mitchell | first4=Nicholas D. | last5=Dursun | first5=Serdar M. | last6=Baker | first6=Glen B. | title=D-Serine: Potential Therapeutic Agent and/or Biomarker in Schizophrenia and Depression? | journal=Frontiers in Psychiatry | date=6 February 2019 | volume=10 | page=25 | issn=1664-0640 | doi=10.3389/fpsyt.2019.00025 | pmid=30787885 | pmc=6372501 | quote=D-Serine is more potent than glycine as a coagonist at the NMDA receptor, has a regional distribution in the brain that is similar to that of NMDA receptors and appears to be more closely associated with synaptic NMDA receptors than glycine (which is more closely associated with non-synaptic NMDA receptors).| doi-access=free }}</ref><ref name="Wolosker 2020">{{cite journal | last1=Wolosker | first1=Herman | last2=Balu | first2=Darrick T. | title=D-Serine as the gatekeeper of NMDA receptor activity: implications for the pharmacologic management of anxiety disorders | journal=Translational Psychiatry | volume=10 | issue=1 | date=9 June 2020 | page=184 | issn=2158-3188 | doi=10.1038/s41398-020-00870-x | pmid=32518273 | pmc=7283225 | quote=D-Serine is functionally a more potent activator of synaptic NMDARs than glycine, and mounting evidence suggests that it serves as the major NMDAR co-agonist in limbic brain regions implicated in neuropsychiatric disorders.}}</ref> However, D-serine has been shown to work as an antagonist/inverse co-agonist of [[NMDA receptor|''t''-NMDA receptors]] through the glycine binding site on the GluN3 subunit.<ref>{{cite journal |last1=Pilli |first1=J. |last2=Kumar |first2=S. S. |date=2012-10-11 |title=Triheteromeric N-methyl-D-aspartate receptors differentiate synaptic inputs onto pyramidal neurons in somatosensory cortex: involvement of the GluN3A subunit |journal=Neuroscience |volume=222 |pages=75–88 |doi=10.1016/j.neuroscience.2012.07.020 |issn=1873-7544 |pmid=22814002|s2cid=23158971 }}</ref><ref>{{cite journal |last1=Beesley |first1=Stephen |last2=Kumar |first2=Sanjay S. |date=2023-11-01 |title=The t-N-methyl-d-aspartate receptor: Making the case for d-Serine to be considered its inverse co-agonist |journal=Neuropharmacology |volume=238 |article-number=109654 |doi=10.1016/j.neuropharm.2023.109654 |issn=1873-7064 |pmid=37437688|doi-access=free }}</ref>

== Ligands ==
<small>D</small>-serine was thought to exist only in bacteria until relatively recently; it was the second <small>D</small> amino acid discovered to naturally exist in humans, present as a signaling molecule in the brain, soon after the discovery of [[aspartate|<small>D</small>-aspartate]]. Had <small>D</small> amino acids been discovered in humans sooner, the glycine site on the NMDA receptor might instead be named the <small>D</small>-serine site.<ref>{{cite journal | vauthors = Mothet JP, Parent AT, Wolosker H, Brady RO, Linden DJ, Ferris CD, Rogawski MA, Snyder SH | title = D-Serine is an endogenous ligand for the glycine site of the ''N''-methyl-D-aspartate receptor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 9 | pages = 4926–4931 | date = Apr 2000 | pmid = 10781100 | pmc = 18334 | doi = 10.1073/pnas.97.9.4926 | bibcode = 2000PNAS...97.4926M | doi-access = free }}</ref> Apart from central nervous system, <small>D</small>-serine plays a signaling role in peripheral tissues and organs such as cartilage,<ref>{{cite journal | vauthors = Takarada T, Hinoi E, Takahata Y, Yoneda Y | title = Serine racemase suppresses chondrogenic differentiation in cartilage in a Sox9-dependent manner | journal = Journal of Cellular Physiology | volume = 215 | issue = 2 | pages = 320–328 | date = May 2008 | pmid = 17929246 | doi = 10.1002/jcp.21310 | s2cid = 45669104 }}</ref> kidney,<ref>{{cite journal | vauthors = Ma MC, Huang HS, Chen YS, Lee SH | title = Mechanosensitive ''N''-methyl-D-aspartate receptors contribute to sensory activation in the rat renal pelvis | journal = Hypertension | volume = 52 | issue = 5 | pages = 938–944 | date = Nov 2008 | pmid = 18809793 | doi = 10.1161/HYPERTENSIONAHA.108.114116 | doi-access = free }}</ref> and corpus cavernosum.<ref>{{cite journal | vauthors = Ghasemi M, Rezania F, Lewin J, Moore KP, Mani AR | title = D-Serine modulates neurogenic relaxation in rat corpus cavernosum | journal = Biochemical Pharmacology | volume = 79 | issue = 12 | pages = 1791–1796 | date = Jun 2010 | pmid = 20170643 | doi = 10.1016/j.bcp.2010.02.007 }}</ref>

=== Gustatory sensation ===
Pure <small>D</small>-serine is an off-white crystalline powder with a very faint musty aroma.  <small>D</small>-Serine is sweet with an additional minor sour taste at medium and high concentrations.<ref name="AAs">{{cite journal | vauthors = Kawai M, Sekine-Hayakawa Y, Okiyama A, Ninomiya Y | title = Gustatory sensation of L- and D-amino acids in humans | journal = Amino Acids | volume = 43 | issue = 6 | pages = 2349–2358 | date = Dec 2012 | pmid = 22588481 | doi = 10.1007/s00726-012-1315-x | s2cid = 17671611 }}</ref>

== Clinical significance ==
Serine deficiency disorders are rare defects in the biosynthesis of the amino acid <small>L</small>-serine. At present three disorders have been reported:

* [[3-phosphoglycerate dehydrogenase deficiency]]
* [[3-phosphoserine phosphatase deficiency]]
* [[Phosphoserine aminotransferase deficiency]]

These enzyme defects lead to severe neurological symptoms such as congenital microcephaly and severe psychomotor retardation and in addition, in patients with 3-phosphoglycerate dehydrogenase deficiency to intractable seizures. These symptoms respond to a variable degree to treatment with <small>L</small>-serine, sometimes combined with glycine.<ref>{{cite journal| author = de Koning TJ| title = Treatment with amino acids in serine deficiency disorders | journal= [[Journal of Inherited Metabolic Disease]]| volume = 29| issue = 2|  pages = 347–351|date=April 2006|pmid = 16763900| doi=10.1007/s10545-006-0269-0| s2cid = 25013468 }}</ref><ref>{{cite journal|author1=Tabatabaie L |author2=Klomp LW |author3=Berger R |author4=de Koning TJ | title = L-Serine synthesis in the central nervous system: a review on serine deficiency disorders| journal = [[Mol Genet Metab]]| volume = 99| issue = 3|  pages = 256–262|date=March 2010| doi= 10.1016/j.ymgme.2009.10.012| pmid = 19963421}}</ref>
Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, as well as for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial [[International Working Group on Neurotransmitter Related Disorders]] (iNTD).<ref>{{cite web|title=Patient registry|url=http://intd-online.org/}}</ref>

Besides disruption of serine biosynthesis, its transport may also become disrupted. One example is [[spastic tetraplegia, thin corpus callosum, and progressive microcephaly]], a disease caused by mutations that affect the function of the [[neutral amino acid transporter A]].

=== Research for therapeutic use ===
The classification of <small>L</small>-serine as a non-essential amino acid has come to be considered as conditional, since vertebrates such as humans cannot always synthesize optimal quantities over entire lifespans.<ref name="MetcalfDunlop2017">{{cite journal|last1=Metcalf|first1=J. S.|last2=Dunlop|first2=R. A.|last3=Powell|first3=J. T.|last4=Banack|first4=S. A.|last5=Cox|first5=P. A.|title=L-Serine: a Naturally-Occurring Amino Acid with Therapeutic Potential|journal=Neurotoxicity Research|volume=33|issue=1|year=2017|pages=213–221|issn=1029-8428|doi=10.1007/s12640-017-9814-x|pmid=28929385|s2cid=20271849}}</ref> Safety of <small>L</small>-serine has been demonstrated in an FDA-approved human phase I clinical trial with Amyotrophic Lateral Sclerosis, [[ALS]], patients (ClinicalTrials.gov identifier: NCT01835782),<ref>{{cite journal | vauthors = Dunlop RA, Cox PA, Banack SA, Rodgers KJ | title = The non-protein amino acid BMAA is misincorporated into human proteins in place of L-serine causing protein misfolding and aggregation | journal = PLOS ONE | year = 2013 | volume = 8 | issue = 9 | article-number = e75376 | pmid = 24086518 | pmc = 3783393 | doi = 10.1371/journal.pone.0075376 | bibcode = 2013PLoSO...875376D | doi-access = free }}</ref><ref>{{cite journal|last1=Levine|first1=Todd D.|last2=Miller|first2=Robert G.|last3=Bradley|first3=Walter G.|last4=Moore|first4=Dan H.|last5=Saperstein|first5=David S.|last6=Flynn|first6=Lynne E.|last7=Katz|first7=Jonathan S.|last8=Forshew|first8=Dallas A.|last9=Metcalf|first9=James S.|last10=Banack|first10=Sandra A.|last11=Cox|first11=Paul A.|date=2017-01-02|title=Phase I clinical trial of safety of L-serine for ALS patients|journal=Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration|language=en|volume=18|issue=1–2|pages=107–111|doi=10.1080/21678421.2016.1221971|pmid=27589995|s2cid=4584977|issn=2167-8421|doi-access=free}}</ref> but treatment of ALS symptoms has yet to be shown. A 2011 meta-analysis found adjunctive [[sarcosine]] to have a medium effect size for negative and total symptoms of schizophrenia.<ref>{{cite journal | vauthors = Singh SP, Singh V | title = Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia | journal = CNS Drugs | volume = 25 | issue = 10 | pages = 859–885 | date = Oct 2011 | pmid = 21936588 | doi = 10.2165/11586650-000000000-00000 | s2cid = 207299820 }}</ref> There also is evidence that <small>L</small>‐serine could acquire a therapeutic role in diabetes.<ref name="HolmBuschard2019">{{cite journal|last1=Holm|first1=Laurits J.|last2=Buschard|first2=Karsten|title=L-serine: a neglected amino acid with a potential therapeutic role in diabetes|journal=APMIS|year=2019|volume=127|issue=10|pages=655–659|issn=0903-4641|doi=10.1111/apm.12987|pmid=31344283|pmc=6851881|doi-access=free}}</ref>
 
<small>D</small>-Serine is being studied in rodents as a potential treatment for schizophrenia.<ref>{{cite journal | vauthors = Balu DT, Li Y, Puhl MD, Benneyworth MA, Basu AC, Takagi S, Bolshakov VY, Coyle JT | title = Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 26 | pages = E2400–E2409 | date = Jun 2013 | pmid = 23729812 | doi = 10.1073/pnas.1304308110 | pmc=3696825| bibcode = 2013PNAS..110E2400B | doi-access = free }}</ref> <small>D</small>-Serine also has been described as a potential biomarker for early [[Alzheimer's disease]] (AD) diagnosis, due to a relatively high concentration of it in the [[cerebrospinal fluid]] of probable AD patients.<ref>{{cite journal | vauthors = Madeira C, Lourenco MV, Vargas-Lopes C, Suemoto CK, Brandão CO, Reis T, Leite RE, Laks J, Jacob-Filho W, Pasqualucci CA, Grinberg LT, Ferreira ST, Panizzutti R | title = D-Serine levels in Alzheimer's disease: implications for novel biomarker development | journal = Translational Psychiatry | volume = 5 | issue = 5 | pages = e561 | date = May 5, 2015 | pmid = 25942042 | doi = 10.1038/tp.2015.52 | pmc=4471283}}</ref> D-serine, which is made in the brain, has been shown to work as an antagonist/inverse co-agonist of ''t''-NMDA receptors mitigating neuron loss in an animal model of [[temporal lobe epilepsy]].<ref name=":3">{{cite journal |last1=Beesley |first1=Stephen |last2=Sullenberger |first2=Thomas |last3=Crotty |first3=Kathryn |last4=Ailani |first4=Roshan |last5=D'Orio |first5=Cameron |last6=Evans |first6=Kimberly |last7=Ogunkunle |first7=Emmanuel O. |last8=Roper |first8=Michael G. |last9=Kumar |first9=Sanjay S. |date=2020-10-02 |title=D-serine mitigates cell loss associated with temporal lobe epilepsy |journal=Nature Communications |volume=11 |issue=1 |page=4966 |doi=10.1038/s41467-020-18757-2 |issn=2041-1723 |pmc=7532172 |pmid=33009404|bibcode=2020NatCo..11.4966B }}</ref>

<small>D</small>-Serine has been theorized as a potential treatment for sensorineural hearing disorders such as [[hearing loss]] and [[tinnitus]].<ref name="Wang 2021">{{cite journal | last1=Wang | first1=Jing | last2=Serratrice | first2=Nicolas | last3=Lee | first3=Cindy J. | last4=François | first4=Florence | last5=Sweedler | first5=Jonathan V. | last6=Puel | first6=Jean-Luc | last7=Mothet | first7=Jean-Pierre | last8=Ruel | first8=Jérôme | title=Physiopathological Relevance of D-Serine in the Mammalian Cochlea | journal=Frontiers in Cellular Neuroscience | publisher=Frontiers Media SA | volume=15 | date=17 December 2021 | article-number=733004 | issn=1662-5102 | doi=10.3389/fncel.2021.733004| pmid=34975405 | pmc=8718999 | doi-access=free }}</ref>

== See also ==
* [[Isoserine]]
* [[Homoserine]] (isothreonine)
* [[Serine octamer cluster]]

== References ==
{{reflist|33em}}

== External links ==
* [http://gmd.mpimp-golm.mpg.de/Spectrums/5aef15ff-bca8-4625-9dc1-a1c891cf43a7.aspx Serine MS Spectrum]

{{Amino acids}}
{{Amino acid metabolism intermediates}}
{{Neurotransmitters}}
{{Ionotropic glutamate receptor modulators}}
{{Glycine receptor modulators}}
{{Lysophospholipid signaling}}

[[Category:Alpha-Amino acids]]
[[Category:Proteinogenic amino acids]]
[[Category:Glucogenic amino acids]]
[[Category:NMDA receptor agonists]]
[[Category:Glycine receptor agonists]]
[[Category:Aldols]]
[[Category:Amino alcohols]]
[[Category:Inhibitory amino acids]]