Phenylalanine

Structural formula
Structure of L- phenylalanine, the naturally occurring enantiomer
General
Surname	Phenylalanine
other names	2-amino-3-phenylpropionic acid 2-amino-3-phenylpropanoic acid PHENYLALANINE ( INCI ) Abbreviations: Phe ( three letter code ) F (one letter code )
Molecular formula	C 9 H 11 NO 2
Brief description	colorless leaflets or needles
External identifiers / databases
CAS number 63-91-2 ( L -enantiomer) 673-06-3 ( D -enantiomer) 150-30-1 ( DL -Racemat) EC number 200-568-1 ECHA InfoCard 100,000,517 PubChem 6140 ChemSpider 5910 DrugBank DB00120 Wikidata Q170545
properties
Molar mass	165.19 g mol −1
Physical state	firmly
density	1.34 g cm −3
Melting point	283–284 ° C ( D -enantiomer, decomposition) 266–267 ° C ( racemate )
pK s value	pK COOH : 1.83 pK NH 3 + : 9.13
solubility	poor in water (27 g l −1 at 20 ° C), methanol and ethanol
safety instructions
GHS labeling of hazardous substances no GHS pictograms H and P phrases H: no H-phrases P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Phenylalanine , abbreviated to Phe or F , is an aromatic α - amino acid with a hydrophobic side chain , which is an essential proteinogenic amino acid for humans . Phenylalanine is structurally derived from alanine and is amphiphilic .

Isomers

Phenylalanine has a stereocenter, so there are two chiral enantiomers . The L -form [synonym: ( S ) -phenylalanine] occurs naturally as a protein component. The D form [synonym: ( R ) -phenylalanine] cannot be used for the metabolism and can only be produced synthetically.

If "phenylalanine" is listed in the following text and in the scientific literature without any additional name ( prefix ), it always means L- phenylalanine .

Enantiomers of phenylalanine
Surname	L - (-) - phenylalanine	D - (+) - phenylalanine
other names	( S ) -phenylalanine	( R ) -phenylalanine
Structural formula
CAS number	63-91-2	673-06-3
	150-30-1 (racemate)
EC number	200-568-1	211-603-5
	205-756-7 (racemate)
ECHA info card	100,000,517	100.010.549
	100.005.234 (racemate)
PubChem	6140	71567
	994 (racemate)
DrugBank	DB00120	DB02556
	- (racemate)
Wikidata	Q170545	Q26841253
	Q27103475 (racemate)

Historical information

L - (-) - phenylalanine was first isolated from legumes in 1879 and was first synthesized in 1882. In 1961 Heinrich Matthaei and Marshall Warren Nirenberg were able to identify that of the amino acid phenylalanine as the first genetic coding unit with the help of the poly-U experiment ; the associated base triplet is UUU .

biosynthesis

L - (-) - phenylalanine is synthesized in plants via the shikimic acid route . The flavonoids can be biosynthesized from L - (-) - phenylalanine via the cinnamic acid route .

In the human body, 4- hydroxylation converts L - (-) - phenylalanine into the proteinogenic amino acid L - tyrosine [synonym: ( S ) - tyrosine ].

Occurrence

Phenylalanine is a component of proteins and peptides . Since it is an essential amino acid for the human organism , it must be ingested in sufficient quantities with food. The following examples for the content of proteinogenically bound phenylalanine each relate to 100 g of the food; the percentage of the total protein is also given:

Food	Total protein	Phenylalanine	proportion of
Peas, dried	24.55 g	1132 mg	4.6%
Chicken breast fillet, raw	21.23 g	0 857 mg	4.0%
Chicken egg	12.57 g	0 680 mg	5.4%
Cow's milk, 3.7% fat	0 3.28 g	0 158 mg	4.8%
Pumpkin seeds	30.23 g	1733 mg	5.7%
Salmon, raw	20.42 g	0 845 mg	4.1%
Wholemeal corn flour	0 6.93 g	0 340 mg	4.9%
Rice, unpeeled	0 7.94 g	0 410 mg	5.2%
Pork, raw	20.95 g	0 881 mg	4.2%
Soybeans, dried	36.49 g	2122 mg	5.8%
Walnuts	15.23 g	0 711 mg	4.7%
Wholemeal wheat flour	13.70 g	0 646 mg	4.7%

All of these foods contain almost exclusively chemically bound L- phenylalanine as a protein component, but no free L- phenylalanine.

The note "contains a source of phenylalanine" printed on some food packaging refers to the presence of the sweetener aspartame , from which phenylalanine is released during the digestive process. This is important for people who have to adhere to a low-phenylalanine diet due to the metabolic disorder phenylketonuria (PKU).

requirement

Phenylalanine is an essential amino acid for humans , so it is not synthesized by the body, but must be ingested in sufficient quantities with food. Since phenylalanine is used by the organism to produce the proteinogenic amino acid tyrosine , the requirement for phenylalanine depends on the tyrosine content of the food. Normal protein-containing foods contain both amino acids in certain proportions. At least for healthy adults, however, it is possible to cover the entire tyrosine requirement through the synthesis from phenylalanine. Depending on the measurement method, the values ​​given in the literature for the average phenylalanine requirement of healthy adults in the complete absence of tyrosine in the diet vary between 38 and 52 mg per kilogram of body weight and day. If, on the other hand, there is an excess of tyrosine, only around 9 mg of phenylalanine per kilogram of body weight and day are required on average. With a phenylalanine to tyrosine ratio of 60:40, the two amino acids are optimally utilized. Sometimes a summarized need is stated based on this. The recommendation of 14 mg per kilogram of body weight and day issued by the FAO / WHO / UNU in 1985 should also be understood in this way.

properties

Zwitterions of L -phenylalanine (left) or D -phenylalanine (right)

Phenylalanine is mainly present as an “inner salt” or zwitterion , the formation of which can be explained by the fact that the proton of the carboxy group migrates to the lone pair of electrons on the nitrogen atom of the amino group .

The zwitterion does not migrate in the electric field because it is uncharged as a whole. Strictly speaking, this is the case at the isoelectric point (at a certain pH value), at which the phenylalanine also has its lowest solubility in water. The isoelectric point of phenylalanine is 5.48.

Free L -phenylalanine has a bitter taste , wherein the detection threshold value at 5 to 7 mmol / L lies. In contrast, free D -phenylalanine tastes sweet, the detection threshold is 1 to 3 mmol / L.

synthesis

L - (-) - Phenylalanine, like other amino acids, is produced on an industrial scale and in considerable quantities. This usually takes place via total synthesis , i.e. without biotechnological aids.

L- phenylalanine is formed in plants via the intermediate stage of shikimic acid in a biological way .

Industrial use

The artificial sweetener aspartame is an L -aspartyl- L -phenylalanyl methyl ester, i.e. the methyl ester of a dipeptide made from L - aspartic acid and L- phenylalanine. The drug nateglinide is made from D- phenylalanine. For the synthesis of the drug alacepril is L -phenylalanine used as the starting material. In stereoselective synthesis, ( S ) - or ( R ) -phenylalanine and their derivatives are important as starting materials and enantioselective catalysts.

medicine

For humans, L- phenylalanine is an essential amino acid that plays an important role in nitrogen metabolism . In the liver, L- phenylalanine - if available in sufficient quantities - can be converted to L - tyrosine . This is catalyzed by phenylalanine hydroxylase , a monooxygenase . The reducing agent here is sapropterin .

However, if the amount of L- phenylalanine is insufficient, tyrosine must also be ingested with food. Since this mechanism no longer works under extreme stress , L - tyrosine must be absorbed more intensely in such cases. The normal daily dose should be 14 mg / kg body weight (an adult). Basically, it is adequately covered by food (see also above). If consumed in excess, phenylalanine can have a laxative effect.

L- phenylalanine is involved in the synthesis of adrenaline , noradrenaline , L- dopa , PEA and melanin . The amino acid L- phenylalanine serves as a starting material for many other substances, e.g. B. for the messenger substance dopamine .

Racemic mixtures of D - and L -phenylalanine (DLPA) are used as painkillers administered or for depression. They have a mood-enhancing effect. The presumed analgesic effect of DL -phenylalanine can be explained by the possible blockade of the enkephalin- breakdown of D -phenylalanine by the enzyme carboxypeptidase A. This makes this one of the rare examples of metabolic effects of D - enantiomers . A genetically -related metabolic disorder is phenylketonuria (PKU), here is L -phenylalanine not fully degraded in the body. The sick can only tolerate a fraction of the normal intake of phenylalanine-containing foods . This applies primarily to natural protein, but also synthetically produced substances such as. B. the sweetener aspartame . People suffering from PKU lack the enzyme phenylalanine hydroxylase. It converts the common L in phenylalanine L to tyrosine. If the enzyme is missing, the concentration of L- phenylalanine in the blood increases to too high a level. This adversely affects the maturation and functioning of the brain. In addition, inflammatory processes can also weaken the activity of the enzyme and lead to moderate hyperphenylalaninemia .

See also

• Homophenylalanine as a structural motif in drugs, especially 2nd generation ACE inhibitors.

literature

• K. Drauz, A. Kleemann , J. Martens : Induction of asymmetry by amino acids. In: Angew. Chem. 94, 1982, pp. 590-613.
• J. Martens: Asymmetric Syntheses with Amino Acids, Topics in Current Chemistry. In: Advances in Chemical Research . 125, 1984, pp. 165-246.
• A. Kleemann, J. Martens, M. Samson, W. Bergstein: Asymmetric Synthesis of Peptides. In: Synthesis . 1981, pp. 740-741.

Web links

Wikibooks: Breaking Down Phenylalanine  - Learning and Teaching Materials

Individual evidence

1. ↑ Entry on PHENYLALANINE in the CosIng database of the EU Commission, accessed on August 19, 2020.
2. ↑ ^{a b c d e f} Entry on L-phenylalanine. In: Römpp Online . Georg Thieme Verlag, accessed on May 29, 2014.
3. ↑ ^{a b c d} data sheet DL-Phenylalanin (PDF) from Merck , accessed on December 21, 2019.
4. ^ Breaking the code. Cold Spring Harbor Laboratory's DNA Learning Center , accessed November 25, 2013.
5. ↑ nutrient database of the US Department of Agriculture , 22nd edition.
6. ↑ Regulation (EC) No. 1333/2008 (PDF) of the European Parliament and of the Council of December 16, 2008 on food additives, Article 23, Paragraph 3b.
7. ↑ PB Pencharz, JW Hsu, RO Ball: Aromatic amino acid requirements in healthy human subjects. In: J. Nutr. 137 (6 Suppl 1); June 2007, pp. 1576S-1578S, PMID 17513429 .
8. ↑ Hans-Dieter Jakubke, Hans Jeschkeit: Amino acids, peptides, proteins. Verlag Chemie, 1982, ISBN 3-527-25892-2 , p. 40.
9. ↑ H.-D. Belitz, W. Grosch, P. Schieberle: Textbook of food chemistry. 5th edition. Springer-Verlag, Berlin / Heidelberg / New York 2001, ISBN 3-540-41096-1 , p. 33.
10. ^ Axel Kleemann, Jürgen Engel, Bernd Kutscher, Dieter Reichert: Pharmaceutical Substances. 4th edition. 2 volumes published by Thieme-Verlag, Stuttgart 2000, ISBN 1-58890-031-2 , pp. 1406-1407; online since 2003 with biannual additions and updates.
11. ↑ Entry on nateglinide in Pharmawiki , accessed on January 28, 2017.
12. ^ Axel Kleemann, Jürgen Engel, Bernd Kutscher, Dieter Reichert: Pharmaceutical Substances. 4th edition. 2 volumes published by Thieme-Verlag, Stuttgart 2000, ISBN 1-58890-031-2 , p. 46; online since 2003 with biannual additions and updates.
13. ^ DW Christianson, S. Mangani, G. Shoham, WN Lipscomb: Binding of D -phenylalanine and D -tyrosine to carboxypeptidase A. In: Journal of Biological Chemistry . 264 (22), 1989, pp. 12849-12853. PMID 2568989 .
14. ↑ G. Neurauter, K. Schröcksnadel, S. Scholl-Bürgi, B. Sperner-Unterweger, C. Schubert, M. Ledochowski, D. Fuchs: Chronic immune stimulation correlates with reduced phenylalanine turnover. In: Current Drug Metabolism . 9 (7), Sept. 2008, pp. 622-627.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !