Phenylalanine is found naturally in the milk ofmammals. It is used in the manufacture of food and drink products and sold as a nutritional supplement as it is a direct precursor to theneuromodulatorphenethylamine. As an essential amino acid, phenylalanine is not synthesizedde 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]
The geneticcodon for phenylalanine was first discovered byJ. Heinrich Matthaei andMarshall W. Nirenberg in 1961. They showed that by usingmRNA to insert multipleuracil repeats into thegenome of thebacteriumE. coli, they could cause the bacterium to produce apolypeptide consisting solely of repeated phenylalanine amino acids. This discovery helped to establish the nature of thecoding relationship that links information stored ingenomic nucleic acid withprotein expression in the living cell.
Good sources of phenylalanine are eggs, chicken, liver, beef, milk, and soybeans.[7] Another common source of phenylalanine is anything sweetened with the artificial sweeteneraspartame, such asdiet drinks,diet foods and medication; the metabolism of aspartame produces phenylalanine as one of the compound'smetabolites.[8]
The Food and Nutrition Board (FNB) of the U.S. Institute of Medicine set Recommended Dietary Allowances (RDAs) foressential 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 was set to 27 mg/kg per day (with no tyrosine), theFAO/WHO/UNU recommendation of 2007 is 25 mg/kg per day (with no tyrosine).[10]
L-Phenylalanine is biologically converted intoL-tyrosine, another one of the DNA-encoded amino acids.L-tyrosine in turn is converted intoL-DOPA, which is further converted intodopamine,norepinephrine (noradrenaline), andepinephrine (adrenaline). The latter three are known as thecatecholamines.
The genetic disorderphenylketonuria (PKU) is the inability to metabolize phenylalanine because of a lack of the enzymephenylalanine 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 calledhyperphenylalaninemia is caused by the inability to synthesize acofactor calledtetrahydrobiopterin, 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 sweeteneraspartame. 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.
DL-Phenylalanine (DLPA) is marketed as a nutritional supplement for its purportedanalgesic andantidepressant activities, which have been supported by clinical trials.[18][19][20]DL-Phenylalanine is a mixture ofD-phenylalanine andL-phenylalanine. The reputed analgesic activity ofDL-phenylalanine may be explained by the possible blockage byD-phenylalanine ofenkephalindegradation by theenzymecarboxypeptidase A.[21][22] Enkephalins act as agonists of themu anddelta opioid receptors, and agonists of these receptors are known to produce antidepressant effects.[23] The mechanism ofDL-phenylalanine's supposed antidepressant activity may also be accounted for in part by theprecursor role ofL-phenylalanine in the synthesis of theneurotransmittersnorepinephrine anddopamine, though clinical trials have not found an antidepressant effect fromL-phenylalanine alone.[18] Elevated brain levels of norepinephrine and dopamine are thought to have an antidepressant effect.D-Phenylalanine is absorbed from thesmall intestine and transported to the liver via theportal circulation. A small amount ofD-phenylalanine appears to be converted toL-phenylalanine.D-Phenylalanine is distributed to the various tissues of the body via thesystemic circulation. It appears to cross theblood–brain barrier less efficiently thanL-phenylalanine, and so a small amount of an ingested dose ofD-phenylalanine is excreted in theurine without penetrating the central nervous system.[24]
L-Phenylalanine is produced for medical, feed, and nutritional applications, such asaspartame, in large quantities by utilizing the bacteriumEscherichia coli, which naturally producesaromatic amino acids like phenylalanine. The quantity ofL-phenylalanine produced commercially has been increased bygenetically engineeringE. coli, such as by altering the regulatorypromoters or amplifying the number ofgenes controlling enzymes responsible for the synthesis of the amino acid.[30]
^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. Retrieved2012-06-04.
^Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family".Trends in Pharmacological Sciences.26 (5):274–281.doi:10.1016/j.tips.2005.03.007.PMID15860375.
^Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D".European Journal of Pharmacology.724:211–218.doi:10.1016/j.ejphar.2013.12.025.PMID24374199.
^Beckmann H, Strauss MA, Ludolph E (1977). "DL-Phenylalanine in depressed patients: An open study".Journal of Neural Transmission.41 (2–3). Springer Science and Business Media LLC:123–134.doi:10.1007/bf01670277.ISSN0300-9564.PMID335027.S2CID5849451.
^Beckmann H, Athen D, Olteanu M, Zimmer R (1979). "DL-Phenylalanine versus imipramine: A double-blind controlled study".Archiv für Psychiatrie und Nervenkrankheiten.227 (1). Springer Science and Business Media LLC:49–58.doi:10.1007/bf00585677.ISSN0003-9373.PMID387000.S2CID23531579.
^Lehmann WD, Theobald N, Fischer R, Heinrich HC (1983-03-14). "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".Clinica Chimica Acta; International Journal of Clinical Chemistry.128 (2–3):181–198.doi:10.1016/0009-8981(83)90319-4.ISSN0009-8981.PMID6851137.
^Mortell KH, Anderson DJ, Lynch JJ, Nelson SL, Sarris K, McDonald H, et al. (March 2006). "Structure-activity relationships of alpha-amino acid ligands for the alpha2delta subunit of voltage-gated calcium channels".Bioorganic & Medicinal Chemistry Letters.16 (5):1138–4111.doi:10.1016/j.bmcl.2005.11.108.PMID16380257.
