Phenylalanine

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Phenylalanine
Skeletal formula
Skeletal formula of L-phenylalanine

L-Phenylalanine at physiological pH
Names
Pronunciation US: /ˌfɛnəlˈælənn/; UK: /ˌfnl-/
IUPAC name
Phenylalanine
Systematic IUPAC name
(S)-2-Amino-3-phenylpropanoic acid
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
100.000.517 Edit this at Wikidata
IUPHAR/BPS
KEGG
UNII
  • InChI=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 checkY
    Key: COLNVLDHVKWLRT-QMMMGPOBSA-N checkY
  • L: Key: COLNVLDHVKWLRT-QMMMGPOBBC
  • D/L: Key: COLNVLDHVKWLRT-UHFFFAOYSA-N
  • D: Key: COLNVLDHVKWLRT-MRVPVSSYSA-N
  • L: c1ccc(cc1)C[C@@H](C(=O)O)N
  • D: c1ccc(cc1)C[C@H](C(=O)O)N
  • L Zwitterion: [NH3+][C@@H](CC1=CC=CC=C1)C([O-])=O
  • D Zwitterion: [NH3+][C@H](CC1=CC=CC=C1)C([O-])=O
Properties
C9H11NO2
Molar mass 165.192 g·mol−1
9.97 g/L at 0 °C

14.11 g/L at 25 °C
21.87 g/L at 50 °C
37.08 g/L at 75 °C
68.9 g/L at 100 °C

Acidity (pKa) 1.83 (carboxyl), 9.13 (amino)[2]
Hazards
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Supplementary data page
Phenylalanine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Phenylalanine (symbol Phe or F)

codons
UUU and UUC.

Phenylalanine is found naturally in the milk of mammals. It is used in the manufacture of food and drink products and sold as a nutritional supplement for its analgesic and antidepressant effects. It is a direct precursor to the neuromodulator phenethylamine, a commonly used dietary supplement. As an essential amino acid, phenylalanine is not synthesized 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.[4]

History

The first description of phenylalanine was made in 1879, when Schulze and Barbieri identified a compound with the empirical formula, C9H11NO2, in yellow lupine (Lupinus luteus) seedlings. In 1882, Erlenmeyer and Lipp first synthesized phenylalanine from phenylacetaldehyde, hydrogen cyanide, and ammonia.[5][6]

The genetic

bacterium E. coli, they could cause the bacterium to produce a polypeptide consisting solely of repeated phenylalanine amino acids. This discovery helped to establish the nature of the coding relationship that links information stored in genomic nucleic acid with protein expression
in the living cell.

Dietary sources

Good sources of phenylalanine are eggs, chicken, liver, beef, milk, and soybeans.

diet drinks, diet foods and medication; the metabolism of aspartame produces phenylalanine as one of the compound's metabolites.[8]

Dietary recommendations

The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) for essential amino acids in 2002. For phenylalanine plus tyrosine, for adults 19 years and older, 33 mg/kg body weight/day.[9] In 2005 the DRI is set to 27 mg/kg per day (with no tyrosine), the FAO/WHO/UNU recommendation of 2007 is 25 mg/kg per day (with no tyrosine).[10]

Other biological roles

L-Phenylalanine is biologically converted into L-

catecholamines
.

Phenylalanine uses the same active transport channel as

aromatic amino acid hydroxylase family and nitric oxide synthase
.

Biosynthetic pathways for catecholamines and trace amines in the human brain[12][13][14]
The image above contains clickable links
Phenylalanine in humans may ultimately be metabolized into a range of different substances.

In plants

Phenylalanine is the starting compound used in the synthesis of flavonoids. Lignan is derived from phenylalanine and from tyrosine. Phenylalanine is converted to cinnamic acid by the enzyme phenylalanine ammonia-lyase.[15]

Biosynthesis

Phenylalanine is biosynthesized via the shikimate pathway.

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 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.[medical citation needed]

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"[16] 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.

D-, L- and DL-phenylalanine

The

niacin receptor 2.[17]

DL-Phenylalanine (DLPA) is marketed as a nutritional supplement for its purported

systemic circulation. It appears to cross the blood–brain barrier less efficiently than L-phenylalanine, and so a small amount of an ingested dose of D-phenylalanine is excreted in the urine without penetrating the central nervous system.[24]

L-Phenylalanine is an antagonist at α2δ Ca2+ calcium channels with a Ki of 980 nM.[25]

In the brain, L-phenylalanine is a

Schild regression[28] which is considerably lower than brain L-phenylalanine concentration observed in untreated human phenylketonuria.[29]
L-Phenylalanine also inhibits
synapses in hippocampus and cortex with IC50 of 980 μM, a brain concentration seen in classical phenylketonuria, whereas D-phenylalanine has a significantly smaller effect.[27]

Commercial synthesis

L-Phenylalanine is produced for medical, feed, and nutritional applications, such as

genes controlling enzymes responsible for the synthesis of the amino acid.[30]

Derivatives

Boronophenylalanine (BPA) is a dihydroxyboryl derivative of phenylalanine, used in

neutron capture therapy
.

4-Azido-L-phenylalanine is a protein-incorporated unnatural amino acid used as a tool for bioconjugation in the field of chemical biology.

References

  1. ^
    PMID 25336255
    .
  2. ^ Dawson RM, et al. (1959). Data for Biochemical Research. Oxford: Clarendon Press.
  3. ^ "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 9 October 2008. Retrieved 5 March 2018.
  4. .
  5. ^ Thorpe TE (1913). A Dictionary of Applied Chemistry. Longmans, Green, and Co. pp. 191–193. Retrieved 2012-06-04.
  6. ^ Plimmer RH (1912) [1908]. Plimmer RH, Hopkins FG (eds.). The Chemical Composition of the Proteins. Monographs on Biochemistry. Vol. Part I. Analysis (2nd ed.). London: Longmans, Green and Co. pp. 93–97. Retrieved 2012-06-04.
  7. .
  8. ^ Zeratsky K. "Phenylalanine in diet soda: Is it harmful?". Mayo Clinic. Retrieved 30 April 2019.
  9. .
  10. .
  11. .
  12. .
  13. .
  14. .
  15. .
  16. ^ "Aspartame". UK: Food Standards Agency. Archived from the original on 2012-02-21. Retrieved 2007-06-19.
  17. ^ "D-Phenylalanine: Biological activity". The IUPHAR/BPS Guide to PHARMACOLOGY. Retrieved 27 December 2018.
  18. ^
    S2CID 3077060
    .
  19. .
  20. .
  21. ^ "D-Phenylalanine: Clinical data". The IUPHAR/BPS Guide to PHARMACOLOGY. Retrieved 27 December 2018.
  22. PMID 2568989
    .
  23. .
  24. .
  25. .
  26. .
  27. ^ .
  28. .
  29. .
  30. .

External links