Phenylalanine

Phenylalanine (abbreviated as Phe or F)<a href="http://en.wikipedia.org/wiki/Phenylalanine#cite_note-1" >[2]</a> is an α-<a href="http://en.wikipedia.org/wiki/Amino_acid" title="Amino acid" >amino acid</a> with the <a href="http://en.wikipedia.org/wiki/Chemical_formula" title="Chemical formula" >formula</a> C6H5CH2CH(NH2)COOH.

This <a href="http://en.wikipedia.org/wiki/Essential_amino_acid" title="Essential amino acid" >essential amino acid</a> is classified as <a href="http://en.wikipedia.org/wiki/Nonpolar" title="Nonpolar" class="mw-redirect" >nonpolar</a> because of the <a href="http://en.wikipedia.org/wiki/Hydrophobic" title="Hydrophobic" class="mw-redirect" >hydrophobic</a> nature of the <a href="http://en.wikipedia.org/wiki/Benzyl" title="Benzyl" >benzyl</a> side chain.

L-Phenylalanine (LPA) is an electrically neutral<a href="http://en.wikipedia.org/wiki/Amino_acid" title="Amino acid" >amino acid</a>, one of the twenty common amino acids used to biochemically form <a href="http://en.wikipedia.org/wiki/Protein" title="Protein" >proteins</a>, coded for by <a href="http://en.wikipedia.org/wiki/DNA" title="DNA" >DNA</a>.

The <a href="http://en.wikipedia.org/wiki/Codons" title="Codons" class="mw-redirect" >codons</a> for L-phenylalanine are UUU and UUC.

Phenylalanine is a precursor for <a href="http://en.wikipedia.org/wiki/Tyrosine" title="Tyrosine" >tyrosine</a>, the <a href="http://en.wikipedia.org/wiki/Monoamine" title="Monoamine" class="mw-redirect" >monoamine</a> signaling molecules <a href="http://en.wikipedia.org/wiki/Dopamine" title="Dopamine" >dopamine</a>,<a href="http://en.wikipedia.org/wiki/Norepinephrine" title="Norepinephrine" >norepinephrine</a> (noradrenaline), and <a href="http://en.wikipedia.org/wiki/Epinephrine" title="Epinephrine" >epinephrine</a> (adrenaline), and the skin <a href="http://en.wikipedia.org/wiki/Pigment" title="Pigment" >pigment</a> <a href="http://en.wikipedia.org/wiki/Melanin" title="Melanin" >melanin</a>.

Phenylalanine is found naturally in the breast milk of mammals. It is used in the manufacture of food and drink products and sold as a nutritional supplement 

for its reputed <a href="http://en.wikipedia.org/wiki/Analgesic" title="Analgesic" >analgesic</a> and <a href="http://en.wikipedia.org/wiki/Antidepressant" title="Antidepressant" >antidepressant</a> effects. It is a direct precursor to the neuromodulator <a href="http://en.wikipedia.org/wiki/Phenylethylamine" title="Phenylethylamine" class="mw-redirect" >phenylethylamine</a>, a commonly used dietary supplement.

L-Phenylalanine is biologically converted into L-<a href="http://en.wikipedia.org/wiki/Tyrosine" title="Tyrosine" >tyrosine</a>, another one of the DNA-encoded amino acids. L-tyrosine in turn is converted into <a href="http://en.wikipedia.org/wiki/L-DOPA" title="L-DOPA" >L-DOPA</a>, which is further converted into <a href="http://en.wikipedia.org/wiki/Dopamine" title="Dopamine" >dopamine</a>, <a href="http://en.wikipedia.org/wiki/Norepinephrine" title="Norepinephrine" >norepinephrine</a> (noradrenaline), and <a href="http://en.wikipedia.org/wiki/Epinephrine" title="Epinephrine" >epinephrine</a> (adrenaline). The latter three are known as the <a href="http://en.wikipedia.org/wiki/Catecholamines" title="Catecholamines" class="mw-redirect" >catecholamines</a>.

Phenylalanine uses the same active transport channel as <a href="http://en.wikipedia.org/wiki/Tryptophan" title="Tryptophan" >tryptophan</a> to cross the

<a href="http://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier" title="Blood–brain barrier" >blood–brain barrier</a>, and, in large quantities, interferes with the production of <a href="http://en.wikipedia.org/wiki/Serotonin" title="Serotonin" >serotonin</a>.

<h3 >In plants</h3>

Phenylalanine is the starting compound used in the <a href="http://en.wikipedia.org/wiki/Flavonoid_biosynthesis" title="Flavonoid biosynthesis" >flavonoid biosynthesis</a>. <a href="http://en.wikipedia.org/wiki/Lignan" title="Lignan" >Lignan</a> is

derived from phenylalanine and from <a href="http://en.wikipedia.org/wiki/Tyrosine" title="Tyrosine" >tyrosine</a>. Phenylalanine is converted to <a href="http://en.wikipedia.org/wiki/Cinnamic_acid" title="Cinnamic acid" >cinnamic acid</a> by the enzyme <a href="http://en.wikipedia.org/wiki/Phenylalanine_ammonia-lyase" title="Phenylalanine ammonia-lyase" >phenylalanine ammonia-lyase</a>.<a href="http://en.wikipedia.org/wiki/Phenylalanine#cite_note-Nelson-2" >[3]</a>

<h2 >Phenylketonuria</h2>

The genetic disorder <a href="http://en.wikipedia.org/wiki/Phenylketonuria" title="Phenylketonuria" >phenylketonuria</a> (PKU) is the inability to metabolize phenylalanine. Individuals with this disorder are known as "phenylketonurics" and must regulate their intake of phenylalanine. A (rare) "variant form" of phenylketonuria called <a href="http://en.wikipedia.org/wiki/Hyperphenylalaninemia" title="Hyperphenylalaninemia" >hyperphenylalaninemia</a> is caused by the inability to synthesize a <a href="http://en.wikipedia.org/wiki/Coenzyme" title="Coenzyme" class="mw-redirect" >coenzyme</a> called <a href="http://en.wikipedia.org/wiki/Biopterin" title="Biopterin" >biopterin</a>, 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. Individuals who cannot metabolize phenylalanine must monitor their intake of protein to control the buildup of phenylalanine as their bodies convert protein into its component amino acids.

Phenylketonurics often use blood tests to monitor the amount of phenylalanine in their blood. Lab results may report phenylalanine levels in different units, including mg/dL and umol/L. One mg/dL of phenylalanine is approximately equivalent to 60 umol/L.

A non-food source of phenylalanine is the artificial sweetener <a href="http://en.wikipedia.org/wiki/Aspartame" title="Aspartame" >aspartame</a>. This compound, sold under the trade names Equal and NutraSweet, is metabolized by the body into several chemical byproducts including phenylalanine. The breakdown problems phenylketonurics have with protein and the attendant build up 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" <a href="http://en.wikipedia.org/wiki/Phenylalanine#cite_note-3" >[4]</a> 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 aid individuals who suffer from <a href="http://en.wikipedia.org/wiki/Phenylketonuria" title="Phenylketonuria" >PKU</a> so that they can avoid such foods.

Geneticists have recently sequenced the genome of <a href="http://en.wikipedia.org/wiki/Macaques" title="Macaques" class="mw-redirect" >macaques</a>. Their investigations have found "some instances where the normal form of the macaque protein looks like the diseased human protein" including markers for PKU.<a href="http://en.wikipedia.org/wiki/Phenylalanine#cite_note-4" >[5]</a>

<h2 >D- and DL-phenylalanine</h2>

The <a href="http://en.wikipedia.org/wiki/Stereoisomer" title="Stereoisomer" class="mw-redirect" >stereoisomer</a> D-phenylalanine (DPA) can be produced by conventional <a href="http://en.wikipedia.org/wiki/Organic_synthesis" title="Organic synthesis" >organic synthesis</a>, either as a

single <a href="http://en.wikipedia.org/wiki/Enantiomer" title="Enantiomer" >enantiomer</a> or as a component of the <a href="http://en.wikipedia.org/wiki/Racemic" title="Racemic" class="mw-redirect" >racemic</a> mixture. It does not participate in <a href="http://en.wikipedia.org/wiki/Protein_biosynthesis" title="Protein biosynthesis" >protein biosynthesis</a> although it is found in proteins in small amounts - particularly aged proteins and food proteins that have been <a href="http://en.wikipedia.org/wiki/Processed_food" title="Processed food" class="mw-redirect" >processed</a>.

The biological functions of D-amino acids remain unclear although some, such as D-phenylalanine, may have <a href="http://en.wikipedia.org/wiki/Pharmacological_activity" title="Pharmacological activity" class="mw-redirect" >pharmacological activity</a>.[<a href="http://en.wikipedia.org/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed" >citation needed</a>] D-phenylalanine, in particular, has been postulated to inhibit the enzymes that breakdown endorphins, giving it a potential analgesic profile.

DL-Phenylalanine (DLPA) is marketed as a nutritional supplement for its supposed <a href="http://en.wikipedia.org/wiki/Analgesic" title="Analgesic" >analgesic</a> and <a href="http://en.wikipedia.org/wiki/Antidepressant" title="Antidepressant" >antidepressant</a> activities.

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 <a href="http://en.wikipedia.org/wiki/Enkephalin" title="Enkephalin" >enkephalin</a> (endorphin) <a href="http://en.wikipedia.org/wiki/Chemical_decomposition" title="Chemical decomposition" >degradation</a> by the<a href="http://en.wikipedia.org/wiki/Enzyme" title="Enzyme" >enzyme</a> <a href="http://en.wikipedia.org/wiki/Carboxypeptidase_A" title="Carboxypeptidase A" >carboxypeptidase A</a>.<a href="http://en.wikipedia.org/wiki/Phenylalanine#cite_note-5" >[6]</a>

The mechanism of DL-phenylalanine's supposed antidepressant activity may be accounted for by the <a href="http://en.wikipedia.org/wiki/Protein_precursor" title="Protein precursor" >precursor</a> role of L-phenylalanine in the synthesis of the <a href="http://en.wikipedia.org/wiki/Neurotransmitters" title="Neurotransmitters" class="mw-redirect" >neurotransmitters</a> <a href="http://en.wikipedia.org/wiki/Norepinephrine" title="Norepinephrine" >norepinephrine</a> and <a href="http://en.wikipedia.org/wiki/Dopamine" title="Dopamine" >dopamine</a>. Elevated brain levels of norepinephrine and dopamine are thought to have an antidepressant effect. Also, as DL-phenylalanine inhibits endorphin degradation, this leads to an inhibition of GABA release in the ventral tegmental neurons (in the midbrain), which results in greater dopamine release. This can explain the analgesic effects following ingestion.

D-Phenylalanine is absorbed from the small intestine and transported to the liver via the <a href="http://en.wikipedia.org/wiki/Portal_circulation" title="Portal circulation" class="mw-redirect" >portal circulation</a>. 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 <a href="http://en.wikipedia.org/wiki/Systemic_circulation" title="Systemic circulation" >systemic circulation</a>. It appears to cross the <a href="http://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier" title="Blood–brain barrier" >blood–brain barrier</a> less efficiently than L-phenylalanine, and so a small amount of an ingested dose of D-phenylalanine is excreted in the <a href="http://en.wikipedia.org/wiki/Urine" title="Urine" >urine</a> without penetrating the central nervous system.

<h2 >Commercial synthesis</h2>

L-Phenylalanine is produced for medical, feed, and nutritional applications, such as <a href="http://en.wikipedia.org/wiki/Aspartame" title="Aspartame" >Aspartame</a>, in large quantities by utilizing the bacterium <a href="http://en.wikipedia.org/wiki/Escherichia_coli" title="Escherichia coli" >Escherichia coli</a>, which naturally produces <a href="http://en.wikipedia.org/wiki/Aromatic_amino_acid" title="Aromatic amino acid" class="mw-redirect" >aromatic amino acids</a> like phenylalanine. The quantity of L-phenylalanine produced commercially has been increased by <a href="http://en.wikipedia.org/wiki/Genetic_engineering" title="Genetic engineering" >genetically engineering</a> E. coli, such as by altering the regulatory <a href="http://en.wikipedia.org/wiki/Promoter_(biology)" title="Promoter (biology)" class="mw-redirect" >promoters</a> or amplifying the number of <a href="http://en.wikipedia.org/wiki/Genes" title="Genes" class="mw-redirect" >genes</a> controlling enzymes responsible for the synthesis of the amino acid.<a href="http://en.wikipedia.org/wiki/Phenylalanine#cite_note-6" >[7]</a>

<h2 >History</h2>

The first description of phenylalanine was made in 1879, when Schulze and Barbieri identified a compound with the <a href="http://en.wikipedia.org/wiki/Empirical_formula" title="Empirical formula" >empirical formula</a>, C9H11NO2, in yellow lupine (<a href="http://en.wikipedia.org/wiki/Lupinus_luteus" title="Lupinus luteus" >Lupinus luteus</a>) seedlings. In 1882, <a href="http://en.wikipedia.org/wiki/Emil_Erlenmeyer" title="Emil Erlenmeyer" >Ehrlinmeyer</a> and Lipp first synthesized phenylalanine from <a href="http://en.wikipedia.org/wiki/Phenylacetaldehyde" title="Phenylacetaldehyde" >phenylacetaldehyde</a>, hydrogen cyanide, and ammonia.<a href="http://en.wikipedia.org/wiki/Phenylalanine#cite_note-7" >[8]</a><a href="http://en.wikipedia.org/wiki/Phenylalanine#cite_note-8" >[9]</a>

The genetic <a href="http://en.wikipedia.org/wiki/Codon" title="Codon" class="mw-redirect" >codon</a> for phenylalanine was first discovered by <a href="http://en.wikipedia.org/wiki/J.Heinrich_Matthaei" title="J. Heinrich Matthaei" >J. Heinrich Matthaei</a> and <a href="http://en.wikipedia.org/wiki/Marshall_W.Nirenberg" title="Marshall W. Nirenberg" class="mw-redirect" >Marshall W. Nirenberg</a> in 1961. They showed that by using m-<a href="http://en.wikipedia.org/wiki/RNA" title="RNA" >RNA</a> to insert multiple <a href="http://en.wikipedia.org/wiki/Uracil" title="Uracil" >uracil</a>repeats into the <a href="http://en.wikipedia.org/wiki/Genome" title="Genome" >genome</a> of the bacterium <a href="http://en.wikipedia.org/wiki/Escherichia_coli" title="Escherichia coli" >E. coli</a>, 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 <a href="http://en.wikipedia.org/wiki/Genome" title="Genome" >genomic</a> nucleic acid with <a href="http://en.wikipedia.org/wiki/Proteome" title="Proteome" >protein expression</a> in the living cell.

<ul >

<li ><a href="http://en.wikipedia.org/wiki/Hyperphenylalanemia" title="Hyperphenylalanemia" class="mw-redirect" >Hyperphenylalanemia</a></li>

</ul>

Phenylalanine

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