Editing Phenylalanine

{{short description|Type of α-amino acid}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{chembox
| pronounce      = {{IPAc-en|US|ˌ|f|ɛ|n|əl|ˈ|æ|l|ə|n|iː|n|audio=LL-Q1860 (eng)-Naomi Persephone Amethyst (NaomiAmethyst)-phenylalanine.wav}}; {{IPAc-en|UK|ˌ|f|iː|n|aɪ|l|-}}
| ImageFile      = L-Phenylalanin - L-Phenylalanine.svg
| ImageClass     = skin-invert
| ImageName      = Skeletal formula
| ImageCaption   = [[Skeletal formula]] of <small>L</small>-phenylalanine
| ImageFile1     = 1PhenylalanineAtPhysiologicalpH.svg
| ImageClass1     = skin-invert
| ImageSize1     = 180px
| ImageCaption1  = <small>L</small>-Phenylalanine at physiological pH
| ImageFileL2    = Phenylalanine-from-xtal-3D-bs-17.png
| ImageSizeL2    = 120px
| ImageCaptionL2 = [[Ball-and-stick model]]<ref name="Ihlefeldt">{{ cite journal | title = The Polymorphs of L-Phenylalanine | first1 = Franziska Stefanie | last1 = Ihlefeldt | first2 = Fredrik Bjarte | last2 = Pettersen | first3 = Aidan | last3 = von Bonin | first4 = Malgorzata | last4 = Zawadzka | first5 = Prof. Carl Henrik | last5 = Görbitz | journal = [[Angewandte Chemie International Edition|Angew. Chem. Int. Ed.]] | volume = 53 | issue = 49 | pages = 13600–13604 | year = 2014 | doi = 10.1002/anie.201406886 | pmid = 25336255}}</ref>
| ImageFileR2    = Phenylalanine-from-xtal-3D-sf.png
| ImageSizeR2    = 120px
| ImageCaptionR2 = [[Space-filling model]]<ref name="Ihlefeldt" />
| SystematicName = (''S'')-2-Amino-3-phenylpropanoic acid
| IUPACName      = Phenylalanine
| 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 -->
|IUPHAR_ligand = 3313
|UNII1_Ref = {{fdacite|correct|FDA}}
|UNII1 = 8P946UF12S
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = 47E5O17Y3R
|UNII2_Ref = {{fdacite|correct|FDA}}
|UNII2 = 032K16VRCU
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 301523
|KEGG_Ref = {{keggcite|correct|kegg}}
|KEGG = D00021
|InChIKey = COLNVLDHVKWLRT-QMMMGPOBBC
|SMILES = c1ccc(cc1)C[C@@H](C(=O)O)N
|SMILES2 = c1ccc(cc1)C[C@H](C(=O)O)N
|SMILES3 = [NH3+][C@@H](CC1=CC=CC=C1)C([O-])=O
|SMILES3_Comment = L [[Zwitterion]]
|SMILES4 = [NH3+][C@H](CC1=CC=CC=C1)C([O-])=O
|SMILES4_Comment = D [[Zwitterion]]
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C9H11NO2/c10-8(9(11)12)6-7-4-2-1-3-5-7/h1-5,8H,6,10H2,(H,11,12)/t8-/m0/s1
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = COLNVLDHVKWLRT-QMMMGPOBSA-N
|InChIKey1 = COLNVLDHVKWLRT-UHFFFAOYSA-N
|InChIKey2 = COLNVLDHVKWLRT-MRVPVSSYSA-N
|CASNo1 = 150-30-1
|CASNo1_Ref = {{cascite|correct|CAS}}
|CASNo_Ref = {{cascite|correct|CAS}}
|CASNo = 63-91-2
|CASNo2_Ref = {{cascite|correct|CAS}}
|CASNo2 = 673-06-3
|PubChem = 6140
|PubChem1 = 994
|PubChem2 = 71567
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID = 5910
|ChemSpiderID1_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID1 = 969
|ChemSpiderID2_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID2 = 64639
|DrugBank_Ref = {{drugbankcite|correct|drugbank}}
|DrugBank=DB00120
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI = 17295
|ChEBI1 = 28044
|ChEBI2_Ref = {{ebicite|correct|EBI}}
|ChEBI2 = 16998
}}
| Section2       = {{Chembox Properties
|C=9 | H=11 | N=1 | O=2
|pKa=1.83 (carboxyl), 9.13 (amino)<ref>{{ cite book | vauthors = Dawson RM | title = Data for Biochemical Research | year = 1959 | location = Oxford | publisher = Clarendon Press |display-authors=etal}}</ref> | Solubility = 9.97 g/L at 0 °C {{Break}}
14.11 g/L at 25 °C {{Break}}
21.87 g/L at 50 °C {{Break}}
37.08 g/L at 75 °C {{Break}}
68.9 g/L at 100 °C
}}
| Section3       = {{Chembox Hazards
|NFPA-H = 2
|NFPA-F = 1
|NFPA-R = 0
}}
}}
[[File:Phenylalanine-spin.gif|thumb|Phenylalanine ball and stick model spinning]]
'''Phenylalanine''' (symbol '''Phe''' or '''F''')<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 essential α-[[amino acid]] with the [[chemical formula|formula]] {{chem|C|9|H|11|N|O|2}}. It can be viewed as a [[benzyl]] group [[substituent|substituted]] for the [[methyl group]] of [[alanine]], or a [[phenyl]] group in place of a terminal hydrogen of alanine. This [[essential amino acid]] is classified as neutral, and [[chemical polarity|nonpolar]] because of the inert and [[hydrophobic]] nature of the [[benzyl]] side chain. The [[chirality (chemistry)#Naming conventions|<small>L</small>-isomer]] is used to biochemically form [[protein]]s coded for by [[DNA]]. Phenylalanine is a precursor for [[tyrosine]], the [[monoamine neurotransmitter]]s [[dopamine]], [[norepinephrine]] (noradrenaline), and [[epinephrine]] (adrenaline), and the [[biological pigment]] [[melanin]]. It is [[Genetic code|encoded]] by the [[messenger RNA]] [[codons]] UUU and UUC.

Phenylalanine is found naturally in the milk of [[mammal]]s. It is used in the manufacture of food and drink products and sold as a nutritional supplement  as it is a direct precursor to the [[neuromodulation|neuromodulator]] [[phenethylamine]]. As an essential amino acid, phenylalanine is not synthesized [[De novo synthesis|de novo]] in humans and other animals, who must ingest phenylalanine or phenylalanine-containing proteins.

The one-letter symbol F was assigned to phenylalanine for its phonetic similarity.<ref name=":0">{{Cite journal |date=10 July 1968 |title=IUPAC-IUB Commission on Biochemical Nomenclature A One-Letter Notation for Amino Acid Sequences |url=https://www.jbc.org/article/S0021-9258(19)34176-6/pdf |journal=Journal of Biological Chemistry |language=en |volume=243 |issue=13 |pages=3557–3559 |doi=10.1016/S0021-9258(19)34176-6|doi-access=free }}</ref>

==History==
The first description of phenylalanine was made in 1879, when [[Ernst Schulze (chemist)|Schulze]] and Barbieri identified a compound with the [[empirical formula]], C<sub>9</sub>H<sub>11</sub>NO<sub>2</sub>, in [[Lupinus luteus|yellow lupine]] (''Lupinus luteus'') seedlings. In 1882, [[Emil Erlenmeyer|Erlenmeyer]] and Lipp first synthesized phenylalanine from [[phenylacetaldehyde]], [[hydrogen cyanide]], and [[ammonia]].<ref>{{ cite book | vauthors = Thorpe TE | author-link = Thomas Edward Thorpe | title = A Dictionary of Applied Chemistry | url = https://archive.org/details/bub_gb_6uVYAAAAYAAJ | access-date = 2012-06-04 | year = 1913 | publisher = Longmans, Green, and Co. | pages = [https://archive.org/details/bub_gb_6uVYAAAAYAAJ/page/n202 191]–193 }}</ref><ref>{{ cite book | 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=PA93 | access-date = 2012-06-04 | edition = 2nd | series = Monographs on Biochemistry | volume = Part I. Analysis | orig-year = 1908 | year = 1912 | publisher = Longmans, Green and Co. | location = London | pages = 93–97 }}</ref>

The genetic [[codon]] for phenylalanine was first discovered by [[J. Heinrich Matthaei]] and [[Marshall W. Nirenberg]] in 1961. They showed that by using [[messenger RNA|mRNA]] to insert multiple [[uracil]] repeats into the [[genome]] of the [[bacterium]] ''[[Escherichia coli|E. coli]]'', they could cause the bacterium to produce a [[peptide|polypeptide]] consisting solely of repeated phenylalanine amino acids. This discovery helped to establish the nature of the [[coding strand|coding]] relationship that links information stored in [[genome|genomic]] nucleic acid with [[proteome|protein expression]] in the living cell.

==Dietary sources==
Good sources of phenylalanine are eggs, chicken, liver, beef, milk, and soybeans.<ref name="RossRoth1991">{{cite book | first1 = Harvey M. | last1 = Ross | first2 = June | last2 = Roth | title = The Mood Control Diet: 21 Days to Conquering Depression and Fatigue | url = https://books.google.com/books?id=hHWQCZvGUMEC | date = 1 April 1991 | publisher = Simon & Schuster | isbn = 978-0-13-590449-7 | page = 59 }}</ref> Another common source of phenylalanine is anything sweetened with the artificial sweetener [[aspartame]], such as [[diet drink]]s, [[diet food]]s and medication; the metabolism of aspartame produces phenylalanine as one of the compound's [[metabolite]]s.<ref>{{cite web |last1=Zeratsky |first1=Katherine |title=Phenylalanine in diet soda: Is it harmful? |url=https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/phenylalanine/faq-20058361 |website=Mayo Clinic |access-date=30 April 2019}}</ref>

==Dietary recommendations==
The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) for [[essential amino acid]]s in 2002. For phenylalanine plus tyrosine, for adults 19 years and older, 33&nbsp;mg/kg body weight/day.<ref name="DRItext">{{cite book | last1 = Institute of Medicine | title = Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids | chapter = Protein and Amino Acids | publisher = The National Academies Press | year = 2002 | location = Washington, DC | pages = 589–768 | doi = 10.17226/10490 | isbn = 978-0-309-08525-0 | chapter-url = https://www.nap.edu/read/10490/chapter/12| author1-link = Institute of Medicine }}</ref> In 2005 the DRI is set to 27&nbsp;mg/kg per day  (with no tyrosine), the [[Food and Agriculture Organization|FAO]]/[[World Health Organization|WHO]]/[[United Nations University|UNU]] recommendation of 2007 is 25&nbsp;mg/kg per day (with no tyrosine).<ref>{{Cite journal |last1=Elango |first1=Rajavel |last2=Ball |first2=Ronald O. |last3=Pencharz |first3=Paul B. |date=August 2012 |title=Recent advances in determining protein and amino acid requirements in humans |journal=British Journal of Nutrition |language=en |volume=108 |issue=S2 |pages=S22–S30 |doi=10.1017/S0007114512002504 |pmid=23107531 |issn=0007-1145|doi-access=free }}</ref>

==Other biological roles==
<small>L</small>-Phenylalanine is biologically converted into <small>L</small>-[[tyrosine]], another one of the DNA-encoded amino acids.  <small>L</small>-tyrosine in turn is converted into [[L-DOPA|<small>L</small>-DOPA]], which is further converted into [[dopamine]], [[norepinephrine]] (noradrenaline), and [[epinephrine]] (adrenaline). The latter three are known as the [[catecholamines]].

Phenylalanine uses the same active transport channel as [[tryptophan]] to cross the [[blood–brain barrier]]. In excessive quantities, supplementation can interfere with the production of [[serotonin]] and other [[aromatic amino acid]]s<ref>{{Cite journal |last1=Eriksson |first1=Johan G |last2=Guzzardi |first2=Maria-Angela |last3=Iozzo |first3=Patricia |last4=Kajantie |first4=Eero |last5=Kautiainen |first5=Hannu |last6=Salonen |first6=Minna K |date=2017-01-01 |title=Higher serum phenylalanine concentration is associated with more rapid telomere shortening in men |journal=The American Journal of Clinical Nutrition |volume=105 |issue=1 |pages=144–150 |doi=10.3945/ajcn.116.130468 |pmid=27881392 |issn=0002-9165|doi-access=free }}</ref> as well as [[nitric oxide]] due to the overuse (eventually, limited availability) of the associated cofactors, [[iron]] or [[tetrahydrobiopterin]]. {{citation needed|date=December 2018}} The corresponding enzymes for those compounds are the [[aromatic amino acid hydroxylase]] family and [[nitric oxide synthase]].{{Phenylalanine biosynthesis|caption=Phenylalanine in humans may ultimately be metabolized into a range of different substances.}}<!--
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===In plants===
Phenylalanine is the starting compound used in the [[biosynthesis|synthesis]] of  [[flavonoid]]s.  [[Lignan]] is derived from phenylalanine and from [[tyrosine]]. Phenylalanine is converted to [[cinnamic acid]] by the enzyme [[phenylalanine ammonia-lyase]].<ref name=Nelson>{{cite book | vauthors = Nelson DL, Cox MM | title = Lehninger, Principles of Biochemistry | edition = 3rd | publisher = Worth Publishing | location = New York | year = 2000 | isbn = 1-57259-153-6 | url-access = registration | url = https://archive.org/details/lehningerprincip01lehn }}</ref>

==Biosynthesis==
Phenylalanine is biosynthesized via the [[shikimate pathway]].

==Phenylketonuria==
{{main|Phenylketonuria}}
The genetic disorder [[phenylketonuria]] (PKU) is the inability to metabolize phenylalanine because of a lack of the enzyme [[phenylalanine hydroxylase]]. Individuals with this disorder are known as "phenylketonurics" and must regulate their intake of phenylalanine. Phenylketonurics often use blood tests to monitor the amount of phenylalanine in their blood.  Lab results may report phenylalanine levels using either mg/dL and μmol/L. One mg/dL of phenylalanine is approximately equivalent to 60 μmol/L.

A (rare) "variant form" of phenylketonuria called [[hyperphenylalaninemia]] is caused by the inability to synthesize a [[Cofactor (biochemistry)|cofactor]] called [[tetrahydrobiopterin]], which can be supplemented. Pregnant women with hyperphenylalaninemia may show similar symptoms of the disorder (high levels of phenylalanine in blood), but these indicators will usually disappear at the end of gestation.  Pregnant women with PKU must control their blood phenylalanine levels even if the fetus is heterozygous for the defective gene because the fetus could be adversely affected due to hepatic immaturity.{{medcn|date=April 2016}}

A non-food source of phenylalanine is the artificial sweetener [[aspartame]]. This compound is metabolized by the body into several chemical byproducts including phenylalanine. The breakdown problems phenylketonurics have with the buildup of phenylalanine in the body also occurs with the ingestion of aspartame, although to a lesser degree. Accordingly, all products in Australia, the U.S. and Canada that contain aspartame must be labeled: "Phenylketonurics: Contains phenylalanine." In the UK, foods containing aspartame must carry ingredient panels that refer to the presence of "aspartame or E951"<ref>{{cite web | url = http://www.food.gov.uk/safereating/chemsafe/additivesbranch/sweeteners/55174#h_4 | title = Aspartame | publisher = Food Standards Agency | location = UK | access-date = 2007-06-19 | archive-date = 2012-02-21 | archive-url = https://web.archive.org/web/20120221223646/http://www.food.gov.uk/safereating/chemsafe/additivesbranch/sweeteners/55174#h_4 | url-status = dead }}</ref> and they must be labeled with a warning "Contains a source of phenylalanine." In Brazil, the label "Contém Fenilalanina" (Portuguese for "Contains Phenylalanine") is also mandatory in products which contain it. These warnings are placed to help individuals avoid such foods.

==<small>D</small>-, <small>L</small>- and <small>DL</small>-phenylalanine==
{{See also|D-Phenylalanine}}

The [[stereoisomer]] [[D-phenylalanine|<small>D</small>-phenylalanine]] (DPA) can be produced by conventional [[organic synthesis]], either as a single [[enantiomer]] or as a component of the [[racemic]] mixture. It does not participate in [[protein biosynthesis]] although it is found in proteins in small amounts - particularly aged proteins and food proteins that have been [[food processing|processed]]. The biological functions of <small>D</small>-amino acids remain unclear, although <small>D</small>-phenylalanine has [[pharmacological activity]] at [[niacin receptor 2]].<ref name="IUPHAR/BPS-bio">{{cite web|title=D-Phenylalanine: Biological activity |url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=5797|website=The IUPHAR/BPS Guide to PHARMACOLOGY|access-date=27 December 2018}}</ref>

<small>DL</small>-Phenylalanine (DLPA) is marketed as a nutritional supplement for its purported [[analgesic]] and [[antidepressant]] activities, which have been supported by clinical trials.<ref name="Wood Reimherr Wender 1985 pp. 21–26">{{cite journal | last1=Wood | first1=David R. | last2=Reimherr | first2=Fred W. | last3=Wender | first3=Paul H. | title=Treatment of attention deficit disorder with DL-phenylalanine | journal=Psychiatry Research | publisher=Elsevier BV | volume=16 | issue=1 | year=1985 | issn=0165-1781 | doi=10.1016/0165-1781(85)90024-1 | pages=21–26| pmid=3903813 | s2cid=3077060 }}</ref><ref name="Beckmann Strauss Ludolph 1977 pp. 123–134">{{cite journal | last1=Beckmann | first1=H. | last2=Strauss | first2=M. A. | last3=Ludolph | first3=E. | title=DL-Phenylalanine in depressed patients: An open study | journal=Journal of Neural Transmission | publisher=Springer Science and Business Media LLC | volume=41 | issue=2–3 | year=1977 | issn=0300-9564 | doi=10.1007/bf01670277 | pages=123–134| pmid=335027 | s2cid=5849451 }}</ref><ref name="Beckmann Athen Olteanu Zimmer 1979 pp. 49–58">{{cite journal | last1=Beckmann | first1=Helmut | last2=Athen | first2=Dieter | last3=Olteanu | first3=Margit | last4=Zimmer | first4=Reinhild | title=DL-Phenylalanine versus imipramine: A double-blind controlled study | journal=Archiv für Psychiatrie und Nervenkrankheiten | publisher=Springer Science and Business Media LLC | volume=227 | issue=1 | year=1979 | issn=0003-9373 | doi=10.1007/bf00585677 | pages=49–58| pmid=387000 | s2cid=23531579 }}</ref>  <small>DL</small>-Phenylalanine is a mixture of <small>D</small>-phenylalanine and <small>L</small>-phenylalanine. The reputed analgesic activity of <small>DL</small>-phenylalanine may be explained by the possible blockage by <small>D</small>-phenylalanine of [[enkephalin]]  [[Chemical decomposition|degradation]] by the [[enzyme]] [[carboxypeptidase A]].<ref name="IUPHAR/BPS-clinical">{{cite web|title=D-Phenylalanine: Clinical data|url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=clinical&ligandId=5797|website=The IUPHAR/BPS Guide to PHARMACOLOGY|access-date=27 December 2018}}</ref><ref>{{cite journal |author1-link=David W. Christianson | vauthors = Christianson DW, Mangani S, Shoham G, Lipscomb WN | title = Binding of D-phenylalanine and D-tyrosine to carboxypeptidase A | journal = The Journal of Biological Chemistry | volume = 264 | issue = 22 | pages = 12849–12853 | date = August 1989 | doi = 10.1016/S0021-9258(18)51564-7 | pmid = 2568989 | url = http://www.jbc.org/content/264/22/12849.full.pdf | doi-access = free }}</ref> Enkephalins act as agonists of the [[mu opioid receptor|mu]] and [[delta opioid receptor]]s, and agonists of these receptors are known to produce antidepressant effects.<ref name="Jelen Stone Young Mehta 2022 p=104800">{{cite journal | last1=Jelen | first1=Luke A. | last2=Stone | first2=James M. | last3=Young | first3=Allan H. | last4=Mehta | first4=Mitul A. | title=The opioid system in depression | journal=Neuroscience & Biobehavioral Reviews | publisher=Elsevier BV | volume=140 | year=2022 | issn=0149-7634 | doi=10.1016/j.neubiorev.2022.104800 | page=104800| pmid=35914624 | pmc=10166717 | s2cid=251163234 | doi-access=free }}</ref> The mechanism of <small>DL</small>-phenylalanine's supposed antidepressant activity may also be accounted for in part by the [[protein precursor|precursor]] role of <small>L</small>-phenylalanine in the synthesis of the [[neurotransmitter]]s [[norepinephrine]] and [[dopamine]], though clinical trials have not found an antidepressant effect from <small>L</small>-phenylalanine alone.<ref name="Wood Reimherr Wender 1985 pp. 21–26"/> Elevated brain levels of norepinephrine and dopamine are thought to have an antidepressant effect.  <small>D</small>-Phenylalanine is absorbed from the [[small intestine]] and transported to the liver via the [[portal circulation]]. A small amount of <small>D</small>-phenylalanine appears to be converted to <small>L</small>-phenylalanine. <small>D</small>-Phenylalanine is distributed to the various tissues of the body via the [[systemic circulation]]. It appears to cross the [[blood–brain barrier]] less efficiently than <small>L</small>-phenylalanine, and so a small amount of an ingested dose of <small>D</small>-phenylalanine is excreted in the [[urine]] without penetrating the central nervous system.<ref>{{Cite journal|last1=Lehmann|first1=W. D.|last2=Theobald|first2=N.|last3=Fischer|first3=R.|last4=Heinrich|first4=H. C.|date=1983-03-14|title=Stereospecificity of phenylalanine plasma kinetics and hydroxylation in man following oral application of a stable isotope-labelled pseudo-racemic mixture of L- and D-phenylalanine|journal=Clinica Chimica Acta; International Journal of Clinical Chemistry|volume=128|issue=2–3|pages=181–198|issn=0009-8981|pmid=6851137|doi=10.1016/0009-8981(83)90319-4}}</ref>

<small>L</small>-Phenylalanine is an antagonist at [[Voltage-gated calcium channel|α<sub>2</sub>δ Ca<sup>2+</sup> calcium channels]] with a K<sub>i</sub> of 980 nM.<ref name="pmid16380257">{{cite journal | vauthors = Mortell KH, Anderson DJ, Lynch JJ, Nelson SL, Sarris K, McDonald H, Sabet R, Baker S, Honore P, Lee CH, Jarvis MF, Gopalakrishnan M | title = Structure-activity relationships of alpha-amino acid ligands for the alpha2delta subunit of voltage-gated calcium channels | journal = Bioorganic & Medicinal Chemistry Letters | volume = 16 | issue = 5 | pages = 1138–4111 | date = March 2006 | pmid = 16380257 | doi = 10.1016/j.bmcl.2005.11.108 }}</ref>

In the brain, <small>L</small>-phenylalanine is a [[competitive antagonist]] at the [[glycine]] binding site of [[NMDA receptor]]<ref>{{cite journal | vauthors = Glushakov AV, Dennis DM, Morey TE, Sumners C, Cucchiara RF, Seubert CN, Martynyuk AE | title = Specific inhibition of ''N''-methyl-D-aspartate receptor function in rat hippocampal neurons by L-phenylalanine at concentrations observed during phenylketonuria | journal = Molecular Psychiatry | volume = 7 | issue = 4 | pages = 359–367 | year = 2002 | pmid = 11986979 | doi = 10.1038/sj.mp.4000976 | doi-access = free }}</ref>  and at the [[glutamate]] binding site of [[AMPA receptor]].<ref name="Glushakov 116–24">{{cite journal | vauthors = Glushakov AV, Dennis DM, Sumners C, Seubert CN, Martynyuk AE | title = L-Phenylalanine selectively depresses currents at glutamatergic excitatory synapses | journal = Journal of Neuroscience Research | volume = 72 | issue = 1 | pages = 116–124 | date = April 2003 | pmid = 12645085 | doi = 10.1002/jnr.10569 | s2cid = 42087834 }}</ref>  At the [[glycine]] binding site of [[NMDA receptor]] <small>L</small>-phenylalanine has an apparent equilibrium dissociation constant (K<sub>B</sub>) of 573 μM estimated by [[Schild regression]]<ref>{{cite journal | vauthors = Glushakov AV, Glushakova O, Varshney M, Bajpai LK, Sumners C, Laipis PJ, Embury JE, Baker SP, Otero DH, Dennis DM, Seubert CN, Martynyuk AE | title = Long-term changes in glutamatergic synaptic transmission in phenylketonuria | journal = Brain | volume = 128 | issue = Pt 2 | pages = 300–307 | date = February 2005 | pmid = 15634735 | doi = 10.1093/brain/awh354 | doi-access = free }}</ref> which is considerably lower than brain <small>L</small>-phenylalanine concentration observed in untreated human [[phenylketonuria]].<ref>{{cite journal | vauthors = Möller HE, Weglage J, Bick U, Wiedermann D, Feldmann R, Ullrich K | title = Brain imaging and proton magnetic resonance spectroscopy in patients with phenylketonuria | journal = Pediatrics | volume = 112 | issue = 6 Pt 2 | pages = 1580–1583 | date = December 2003 | doi = 10.1542/peds.112.S4.1580 | pmid = 14654669 | hdl = 11858/00-001M-0000-0010-A24A-C | s2cid = 2198040 | hdl-access = free }}</ref>
<small>L</small>-Phenylalanine also inhibits [[neurotransmitter]] release at [[glutamatergic]] [[synapses]] in [[hippocampus]] and [[Cerebral cortex|cortex]] with [[IC50|IC<sub>50</sub>]] of 980 μM, a brain concentration seen in classical [[phenylketonuria]], whereas <small>D</small>-phenylalanine has a significantly smaller effect.<ref name="Glushakov 116–24"/>

==Commercial synthesis==
<small>L</small>-Phenylalanine is produced for medical, feed, and nutritional applications, such as [[aspartame]], in large quantities by utilizing the bacterium ''[[Escherichia coli]]'', which naturally produces [[aromatic amino acids]] like phenylalanine.  The quantity of <small>L</small>-phenylalanine produced commercially has been increased by [[genetic engineering|genetically engineering]] ''E. coli'', such as by altering the regulatory [[Promoter (biology)|promoters]] or amplifying the number of [[genes]] controlling enzymes responsible for the synthesis of the amino acid.<ref>{{ cite book | last = Sprenger  | first = G. A. | title = Amino Acid Biosynthesis: Pathways, Regulation and Metabolic Engineering | publisher = Springer  | year = 2007 | edition = 1st  | chapter = Aromatic Amino Acids | pages = 106–113 | isbn = 978-3-540-48595-7 }}</ref>

==Derivatives==
'''Boronophenylalanine''' (BPA) is a dihydroxyboryl derivative of phenylalanine, used in [[neutron capture therapy]].

'''4-Azido-<small>L</small>-phenylalanine''' is a protein-incorporated unnatural amino acid used as a tool for [[bioconjugation]] in the field of [[chemical biology]].

==See also==
* [[Phenylalaninol]]

== References ==
{{reflist|30em|refs =

<!--unused<ref name = "Gibbs_2007">{{cite journal | vauthors = Gibbs RA, Rogers J, Katze MG, Bumgarner R, Weinstock GM, Mardis ER, Remington KA, Strausberg RL, Venter JC, Wilson RK, Batzer MA, Bustamante CD, Eichler EE, Hahn MW, Hardison RC, Makova KD, Miller W, Milosavljevic A, Palermo RE, Siepel A, Sikela JM, Attaway T, Bell S, Bernard KE, Buhay CJ, Chandrabose MN, Dao M, Davis C, Delehaunty KD, Ding Y, Dinh HH, Dugan-Rocha S, Fulton LA, Gabisi RA, Garner TT, Godfrey J, Hawes AC, Hernandez J, Hines S, Holder M, Hume J, Jhangiani SN, Joshi V, Khan ZM, Kirkness EF, Cree A, Fowler RG, Lee S, Lewis LR, Li Z, Liu YS, Moore SM, Muzny D, Nazareth LV, Ngo DN, Okwuonu GO, Pai G, Parker D, Paul HA, Pfannkoch C, Pohl CS, Rogers YH, Ruiz SJ, Sabo A, Santibanez J, Schneider BW, Smith SM, Sodergren E, Svatek AF, Utterback TR, Vattathil S, Warren W, White CS, Chinwalla AT, Feng Y, Halpern AL, Hillier LW, Huang X, Minx P, Nelson JO, Pepin KH, Qin X, Sutton GG, Venter E, Walenz BP, Wallis JW, Worley KC, Yang SP, Jones SM, Marra MA, Rocchi M, Schein JE, Baertsch R, Clarke L, Csürös M, Glasscock J, Harris RA, Havlak P, Jackson AR, Jiang H, Liu Y, Messina DN, Shen Y, Song HX, Wylie T, Zhang L, Birney E, Han K, Konkel MK, Lee J, Smit AF, Ullmer B, Wang H, Xing J, Burhans R, Cheng Z, Karro JE, Ma J, Raney B, She X, Cox MJ, Demuth JP, Dumas LJ, Han SG, Hopkins J, Karimpour-Fard A, Kim YH, Pollack JR, Vinar T, Addo-Quaye C, Degenhardt J, Denby A, Hubisz MJ, Indap A, Kosiol C, Lahn BT, Lawson HA, Marklein A, Nielsen R, Vallender EJ, Clark AG, Ferguson B, Hernandez RD, Hirani K, Kehrer-Sawatzki H, Kolb J, Patil S, Pu LL, Ren Y, Smith DG, Wheeler DA, Schenck I, Ball EV, Chen R, Cooper DN, Giardine B, Hsu F, Kent WJ, Lesk A, Nelson DL, O'brien WE, Prüfer K, Stenson PD, Wallace JC, Ke H, Liu XM, Wang P, Xiang AP, Yang F, Barber GP, Haussler D, Karolchik D, Kern AD, Kuhn RM, Smith KE, Zweig AS | title = Evolutionary and biomedical insights from the rhesus macaque genome | journal = Science | volume = 316 | issue = 5822 | pages = 222–234 | date = April 2007 | pmid = 17431167 | doi = 10.1126/science.1139247  | bibcode = 2007Sci...316..222. | doi-access = free }}</ref>-->

}}

== External links ==
{{Commons category|L-Phenylalanine}}
*[http://gmd.mpimp-golm.mpg.de/Spectrums/53729aa2-297a-4bc7-818b-be4515403113.aspx Phenylalanine mass spectrum]
*[http://www.chemsynthesis.com/base/chemical-structure-453.html Phenylalanine at ChemSynthesis]

{{Amino acids}}
{{Amino acid metabolism intermediates}}
{{Dopaminergics}}
{{Opioidergics}}
{{Phenethylamines}}
{{Chocolate}}

[[Category:Alpha-Amino acids]]
[[Category:Animal products]]
[[Category:Proteinogenic amino acids]]
[[Category:Glucogenic amino acids]]
[[Category:Ketogenic amino acids]]
[[Category:Aromatic amino acids]]
[[Category:Essential amino acids]]
[[Category:Enkephalinase inhibitors]]
[[Category:Phenethylamines]]
[[Category:Dopamine agonists]]
[[Category:Carbonic anhydrase activators]]
[[Category:Monoamine precursors]]
 <!--https://www.ncbi.nlm.nih.gov/pubmed/29478330-->