Phenylalanine

Last updated

Contents

Phenylalanine
Skeletal formula L-Phenylalanin - L-Phenylalanine.svg
Skeletal formula
Skeletal formula of L-phenylalanine
1PhenylalanineAtPhysiologicalpH.svg
L-Phenylalanine at physiological pH
Phenylalanine-from-xtal-3D-bs-17.png
Phenylalanine-from-xtal-3D-sf.png
Names
Pronunciation US: /ˌfɛnəlˈæləniːn/ ; UK: /ˌfiːnaɪl-/
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 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
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 Yes check.svgY
    Key: COLNVLDHVKWLRT-QMMMGPOBSA-N Yes check.svgY
  • 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.svgHealth 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) [3] is an essential α-amino acid with the formula C
9H
11NO
2. It can be viewed as a benzyl group 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 nonpolar because of the inert and hydrophobic nature of the benzyl side chain. The L-isomer is used to biochemically form proteins coded for by DNA. Phenylalanine is a precursor for tyrosine, the monoamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), and the biological pigment melanin. It is encoded by the messenger RNA 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 as it is a direct precursor to the neuromodulator phenethylamine. 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 codon for phenylalanine was first discovered by J. Heinrich Matthaei and Marshall W. Nirenberg in 1961. They showed that by using mRNA to insert multiple uracil repeats into the genome of the 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. [7] Another common source of phenylalanine is anything sweetened with the artificial sweetener aspartame, such as 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-tyrosine, another one of the DNA-encoded amino acids. L-tyrosine in turn is converted into L-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 acids [11] as well as nitric oxide due to the overuse (eventually, limited availability) of the associated cofactors, iron or tetrahydrobiopterin. [ citation needed ] The corresponding enzymes for those compounds are the aromatic amino acid hydroxylase family and nitric oxide synthase.

Biosynthetic pathways for catecholamines and trace amines in the human brain [12] [13] [14]
Catecholamine and trace amine biosynthesis.svg
Interactive icon.svg
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 stereoisomer D-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 processed. The biological functions of D-amino acids remain unclear, although D-phenylalanine has pharmacological activity at niacin receptor 2. [17]

DL-Phenylalanine (DLPA) is marketed as a nutritional supplement for its purported analgesic and antidepressant activities, which have been supported by clinical trials. [18] [19] [20] DL-Phenylalanine is a mixture of D-phenylalanine and L-phenylalanine. The reputed analgesic activity of DL-phenylalanine may be explained by the possible blockage by D-phenylalanine of enkephalin degradation by the enzyme carboxypeptidase A. [21] [22] Enkephalins act as agonists of the mu and delta opioid receptors, and agonists of these receptors are known to produce antidepressant effects. [23] The mechanism of DL-phenylalanine's supposed antidepressant activity may also be accounted for in part by the precursor role of L-phenylalanine in the synthesis of the neurotransmitters norepinephrine and dopamine, though clinical trials have not found an antidepressant effect from L-phenylalanine alone. [18] Elevated brain levels of norepinephrine and dopamine are thought to have an antidepressant effect. D-Phenylalanine is absorbed from the small intestine and transported to the liver via the portal circulation. A small amount of D-phenylalanine appears to be converted to L-phenylalanine. D-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 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 competitive antagonist at the glycine binding site of NMDA receptor [26] and at the glutamate binding site of AMPA receptor. [27] At the glycine binding site of NMDA receptor L-phenylalanine has an apparent equilibrium dissociation constant (KB) of 573 μM estimated by Schild regression [28] which is considerably lower than brain L-phenylalanine concentration observed in untreated human phenylketonuria. [29] L-Phenylalanine also inhibits neurotransmitter release at glutamatergic 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 aspartame, in large quantities by utilizing the bacterium Escherichia coli , which naturally produces aromatic amino acids like phenylalanine. The quantity of L-phenylalanine produced commercially has been increased by genetically engineering E. coli, such as by altering the regulatory promoters or amplifying the number of 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.

See also

Related Research Articles

<span class="mw-page-title-main">Aspartame</span> Artificial non-saccharide sweetener

Aspartame is an artificial non-saccharide sweetener 200 times sweeter than sucrose and is commonly used as a sugar substitute in foods and beverages. It is a methyl ester of the aspartic acid/phenylalanine dipeptide with brand names NutraSweet, Equal, and Canderel. Discovered in 1965, aspartame was approved by the US Food and Drug Administration (FDA) in 1974 and re-approved in 1981 after its initial approval was briefly revoked.

<span class="mw-page-title-main">Neurotransmitter</span> Chemical substance that enables neurotransmission

A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.

<span class="mw-page-title-main">Phenylketonuria</span> Amino acid metabolic disorder

Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight.

<span class="mw-page-title-main">Tyrosine</span> Amino acid

L-Tyrosine or tyrosine or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is from the Greek tyrós, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. It is called tyrosyl when referred to as a functional group or side chain. While tyrosine is generally classified as a hydrophobic amino acid, it is more hydrophilic than phenylalanine. It is encoded by the codons UAC and UAU in messenger RNA.

<span class="mw-page-title-main">Dopamine</span> Organic chemical that functions both as a hormone and a neurotransmitter

Dopamine is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% of the catecholamine content in the brain. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical, L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons to send signals to other nerve cells. Neurotransmitters are synthesized in specific regions of the brain but affect many regions systemically. The brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, and many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory.

<span class="mw-page-title-main">Catecholamine</span> Class of chemical compounds

A catecholamine is a monoamine neurotransmitter, an organic compound that has a catechol and a side-chain amine.

<span class="mw-page-title-main">Phenylalanine hydroxylase</span> Mammalian protein found in Homo sapiens

Phenylalanine hydroxylase (PAH) (EC 1.14.16.1) is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PAH is one of three members of the biopterin-dependent aromatic amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin (BH4, a pteridine cofactor) and a non-heme iron for catalysis. During the reaction, molecular oxygen is heterolytically cleaved with sequential incorporation of one oxygen atom into BH4 and phenylalanine substrate. In humans, mutations in its encoding gene, PAH, can lead to the metabolic disorder phenylketonuria.

<span class="mw-page-title-main">Monoamine neurotransmitter</span> Monoamine that acts as a neurotransmitter or neuromodulator

Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.

<span class="mw-page-title-main">Phenethylamine</span> Organic compound, a stimulant in humans

Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.

<span class="mw-page-title-main">Tyramine</span> Chemical compound

Tyramine, also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-brain barrier, resulting in only non-psychoactive peripheral sympathomimetic effects following ingestion. A hypertensive crisis can result, however, from ingestion of tyramine-rich foods in conjunction with the use of monoamine oxidase inhibitors (MAOIs).

<small>L</small>-DOPA Chemical compound

l-DOPA, also known as l-3,4-dihydroxyphenylalanine and used medically as levodopa, is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize l-DOPA, make it via biosynthesis from the amino acid l-tyrosine.

Aromatic <small>L</small>-amino acid decarboxylase Class of enzymes

Aromatic L-amino acid decarboxylase, also known as DOPA decarboxylase (DDC), tryptophan decarboxylase, and 5-hydroxytryptophan decarboxylase, is a lyase enzyme, located in region 7p12.2-p12.1.

<span class="mw-page-title-main">Tetrahydrobiopterin</span> Chemical compound

Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN), is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT), melatonin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and is a cofactor for the production of nitric oxide (NO) by the nitric oxide synthases. Chemically, its structure is that of a (dihydropteridine reductase) reduced pteridine derivative (quinonoid dihydrobiopterin).

<span class="mw-page-title-main">Tetrahydrobiopterin deficiency</span> Medical condition

Tetrahydrobiopterin deficiency (THBD, BH4D) is a rare metabolic disorder that increases the blood levels of phenylalanine. Phenylalanine is an amino acid obtained normally through the diet, but can be harmful if excess levels build up, causing intellectual disability and other serious health problems. In healthy individuals, it is metabolised (hydroxylated) into tyrosine, another amino acid, by phenylalanine hydroxylase. However, this enzyme requires tetrahydrobiopterin as a cofactor and thus its deficiency slows phenylalanine metabolism.

<span class="mw-page-title-main">Apigenin</span> Chemical compound

Apigenin (4′,5,7-trihydroxyflavone), found in many plants, is a natural product belonging to the flavone class that is the aglycone of several naturally occurring glycosides. It is a yellow crystalline solid that has been used to dye wool.

<span class="mw-page-title-main">Aromatic amino acid</span> Amino acid having an aromatic ring

An aromatic amino acid is an amino acid that includes an aromatic ring.

<span class="mw-page-title-main">Norepinephrine</span> Catecholamine hormone and neurotransmitter

Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone, neurotransmitter and neuromodulator. The name "noradrenaline" is more commonly used in the United Kingdom and the rest of the world, whereas "norepinephrine" is usually preferred in the United States. "Norepinephrine" is also the international nonproprietary name given to the drug. Regardless of which name is used for the substance itself, parts of the body that produce or are affected by it are referred to as noradrenergic.

<span class="mw-page-title-main">Biopterin-dependent aromatic amino acid hydroxylase</span> Protein family

Biopterin-dependent aromatic amino acid hydroxylases (AAAH) are a family of aromatic amino acid hydroxylase enzymes which includes phenylalanine 4-hydroxylase, tyrosine 3-hydroxylase, and tryptophan 5-hydroxylase. These enzymes primarily hydroxylate the amino acids L-phenylalanine, L-tyrosine, and L-tryptophan, respectively.

<span class="mw-page-title-main">Monoamine precursor</span>

Monoamine precursors are precursors of monoamines and monoamine neurotransmitters in the body. The amino acids L-tryptophan and L-5-hydroxytryptophan are precursors of serotonin and melatonin, while the amino acids L-phenylalanine, L-tyrosine, and L-DOPA (levodopa) are precursors of dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline).

α-Methylphenylalanine Monoamine metabolism inhibitor

α-Methylphenylalanine is an artificial amino acid and a phenethylamine and amphetamine derivative. It is the α-methylated analogue of phenylalanine, the precursor of the catecholamine neurotransmitters, and the amino acid analogue of amphetamine (α-methylphenethylamine), a psychostimulant and monoamine releasing agent.

References

  1. 1 2 Ihlefeldt FS, Pettersen FB, von Bonin A, Zawadzka M, Görbitz PC (2014). "The Polymorphs of L-Phenylalanine". Angew. Chem. Int. Ed. 53 (49): 13600–13604. doi:10.1002/anie.201406886. 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. ↑ "IUPAC-IUB Commission on Biochemical Nomenclature A One-Letter Notation for Amino Acid Sequences". Journal of Biological Chemistry. 243 (13): 3557–3559. 10 July 1968. doi: 10.1016/S0021-9258(19)34176-6 .
  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. ↑ Ross HM, Roth J (1 April 1991). The Mood Control Diet: 21 Days to Conquering Depression and Fatigue. Simon & Schuster. p. 59. ISBN   978-0-13-590449-7.
  8. ↑ Zeratsky K. "Phenylalanine in diet soda: Is it harmful?". Mayo Clinic. Retrieved 30 April 2019.
  9. ↑ Institute of Medicine (2002). "Protein and Amino Acids". Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. pp. 589–768. doi:10.17226/10490. ISBN   978-0-309-08525-0.
  10. ↑ Elango R, Ball RO, Pencharz PB (August 2012). "Recent advances in determining protein and amino acid requirements in humans". British Journal of Nutrition. 108 (S2): S22 –S30. doi: 10.1017/S0007114512002504 . ISSN   0007-1145. PMID   23107531.
  11. ↑ Eriksson JG, Guzzardi MA, Iozzo P, Kajantie E, Kautiainen H, Salonen MK (2017-01-01). "Higher serum phenylalanine concentration is associated with more rapid telomere shortening in men". The American Journal of Clinical Nutrition. 105 (1): 144–150. doi: 10.3945/ajcn.116.130468 . ISSN   0002-9165. PMID   27881392.
  12. ↑ Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacology & Therapeutics. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID   19948186.
  13. ↑ 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. PMID   15860375.
  14. ↑ 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. PMID   24374199.
  15. ↑ Nelson DL, Cox MM (2000). Lehninger, Principles of Biochemistry (3rd ed.). New York: Worth Publishing. ISBN   1-57259-153-6.
  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. 1 2 Wood DR, Reimherr FW, Wender PH (1985). "Treatment of attention deficit disorder with DL-phenylalanine". Psychiatry Research. 16 (1). Elsevier BV: 21–26. doi:10.1016/0165-1781(85)90024-1. ISSN   0165-1781. PMID   3903813. S2CID   3077060.
  19. ↑ 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. ISSN   0300-9564. PMID   335027. S2CID   5849451.
  20. ↑ 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. ISSN   0003-9373. PMID   387000. S2CID   23531579.
  21. ↑ "D-Phenylalanine: Clinical data". The IUPHAR/BPS Guide to PHARMACOLOGY. Retrieved 27 December 2018.
  22. ↑ Christianson DW, Mangani S, Shoham G, Lipscomb WN (August 1989). "Binding of D-phenylalanine and D-tyrosine to carboxypeptidase A" (PDF). The Journal of Biological Chemistry. 264 (22): 12849–12853. doi: 10.1016/S0021-9258(18)51564-7 . PMID   2568989.
  23. ↑ Jelen LA, Stone JM, Young AH, Mehta MA (2022). "The opioid system in depression". Neuroscience & Biobehavioral Reviews. 140. Elsevier BV: 104800. doi: 10.1016/j.neubiorev.2022.104800 . ISSN   0149-7634. PMC   10166717 . PMID   35914624. S2CID   251163234.
  24. ↑ 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. ISSN   0009-8981. PMID   6851137.
  25. ↑ 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. PMID   16380257.
  26. ↑ Glushakov AV, Dennis DM, Morey TE, Sumners C, Cucchiara RF, Seubert CN, et al. (2002). "Specific inhibition of N-methyl-D-aspartate receptor function in rat hippocampal neurons by L-phenylalanine at concentrations observed during phenylketonuria". Molecular Psychiatry. 7 (4): 359–367. doi: 10.1038/sj.mp.4000976 . PMID   11986979.
  27. 1 2 Glushakov AV, Dennis DM, Sumners C, Seubert CN, Martynyuk AE (April 2003). "L-Phenylalanine selectively depresses currents at glutamatergic excitatory synapses". Journal of Neuroscience Research. 72 (1): 116–124. doi:10.1002/jnr.10569. PMID   12645085. S2CID   42087834.
  28. ↑ Glushakov AV, Glushakova O, Varshney M, Bajpai LK, Sumners C, Laipis PJ, et al. (February 2005). "Long-term changes in glutamatergic synaptic transmission in phenylketonuria". Brain. 128 (Pt 2): 300–307. doi: 10.1093/brain/awh354 . PMID   15634735.
  29. ↑ Möller HE, Weglage J, Bick U, Wiedermann D, Feldmann R, Ullrich K (December 2003). "Brain imaging and proton magnetic resonance spectroscopy in patients with phenylketonuria". Pediatrics. 112 (6 Pt 2): 1580–1583. doi:10.1542/peds.112.S4.1580. hdl: 11858/00-001M-0000-0010-A24A-C . PMID   14654669. S2CID   2198040.
  30. ↑ Sprenger GA (2007). "Aromatic Amino Acids". Amino Acid Biosynthesis: Pathways, Regulation and Metabolic Engineering (1st ed.). Springer. pp. 106–113. ISBN   978-3-540-48595-7.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.