phenylalanine

phenylalanine, organic compound, one of the 22 α-amino acids commonly found in animal proteins. Only the l-stereoisomer appears in mammalian protein. It is one of several essential amino acids needed in the diet; human beings cannot synthesize it from simpler metabolites. Young adults need about 31 mg of this amino acid per day per kg (14 mg per lb) of body weight. Phenylalanine can be degraded into simpler compounds by the enzymes of the body and is readily converted to the amino acid tyrosine. Phenylketonuria (PKU), an inherited disease that, if left untreated, results in retarded mental development in children, has been shown to be associated with the lack of activity of the enzyme that converts phenylalanine to tyrosine. This results in the buildup of phenylalanine in the blood, an event leading to several pathological consequences. The incidence of this disease, about one in every 10,000 births, is high enough to have prompted several states to institute regular screening procedures for the detection of the disease in newborns. If diagnosed early the disease can be controlled to a great extent by administering a diet very low in phenylalanine. Phenylalanine contributes to the structure of proteins into which it has been incorporated by the tendency of its side chain to participate in hydrophobic interactions (see isoleucine). This amino acid was first isolated from a natural source (lupine sprouts) in 1879; it was first chemically synthesized in 1882.

One of the essential amino acids, present in many common proteins, especially hemoglobin. It is used in medicine and nutrition and as one of the two amino acids making up aspartame. Persons with phenylketonuria do not metabolize phenylalanine properly and must adhere to a diet free of it.

Learn more about phenylalanine with a free trial on Britannica.com.

Phe redirects here. For the BitTorrent feature, see PHE. For the constellation, see Phoenix (constellation).

Phenylalanine (abbreviated as Phe or F) is an α-amino acid with the formula HO₂CCH(NH₂)CH₂C₆H₅, which is found naturally in the breast milk of mammals and manufactured for food and drink products and are also sold as nutritional supplements for their reputed analgesic and antidepressant effects. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. The codons for L-phenylalanine are UUU and UUC. It is a white, powdery solid. L-Phenylalanine (LPA) is an electrically-neutral amino acid, one of the twenty common amino acids used to biochemically form proteins, coded for by DNA.

Biosynthesis

Breast milk from mammals is rich in phenylalanine. It is also produced by plants and most microorganisms from prephenate, an intermediate on the shikimate pathway.

Prephenate is decarboxylated with loss of the hydroxyl group to give phenylpyruvate. This species is transaminated using glutamate as the nitrogen source to give phenylalanine and α-ketoglutarate.

Other biological roles

L-phenylalanine can also be 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, and, in large quantities, interferes with the production of serotonin.

Lignin is derived from phenylalanine and from tyrosine. Phenylalanine is converted to cinnamic acid by the enzyme phenylalanine ammonia lyase.

Phenylketonuria

The genetic disorder phenylketonuria (PKU) is the inability to metabolize phenylalanine. Individuals with this disorder are known as "phenylketonurics" and must abstain from consumption of phenylalanine. This dietary restriction also applies to pregnant women with hyperphenylalanine (high levels of phenylalanine in blood) because they do not properly metabolize the amino acid phenylalanine. Persons suffering from PKU must monitor their intake of protein to control the buildup of phenylalanine as their bodies convert protein into its component amino acids.

A non food source of phenylalanine is the artificial sweetener aspartame. 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 ingredients panels that refer to the presence of "aspartame or E951" and they must be labeled with a warning "Contains a source of phenylalanine." These warnings are specifically placed to aid individuals who suffer from PKU so that they can avoid such foods.

Geneticists have recently sequenced the genome of macaques. Their investigations have found "some instances where the normal form of the macaque protein looks like the diseased human protein" including markers for PKU.

D- and DL-phenylalanine

The unnatural 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 some, such as D-phenylalanine, may have pharmacological activity.

DL-Phenylalanine is marketed as a nutritional supplement for its supposed analgesic and antidepressant activities. 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. The mechanism of DL-phenylalanine's supposed antidepressant activity may be accounted for by the precursor role of L-phenylalanine in the synthesis of the neurotransmitters, norepinephrine and dopamine. Elevated brain levels of norepinephrine and dopamine are thought to have an antidepressant effect. Following ingestion, 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 efficienciently than L-phenylalanine, and so a small amount of an ingested dose of D-phenylalanine is not absorbed but excreted in the urine.

History

The genetic codon for phenylalanine was first discovered by Marshall W. Nirenberg in 1959. He showed that by using m-RNA to insert multiple uracil repeats into the bacterium E. coli, the bacterium produced a new protein consisting solely of repeated phenylalanine amino acids. This discovery lead to the determination of the relationship between RNA and amino acids, which was foundational to the understanding of the Genetic Code.

References

External links

• Phenylalanine food sources, deficiency symptoms, and general details