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Identification
NameL-Phenylalanine
Accession NumberDB00120  (NUTR00044)
Typesmall molecule
Groupsapproved, nutraceutical
Description

An essential aromatic amino acid that is a precursor of melanin; dopamine; noradrenalin (norepinephrine), and thyroxine. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(S)-2-Amino-3-phenylpropionic acidNot AvailableNot Available
(S)-alpha-Amino-beta-phenylpropionic acidNot AvailableNot Available
3-phenyl-L-alanineNot AvailableNot Available
beta-Phenyl-L-alanineNot AvailableNot Available
FNot AvailableNot Available
L-PhenylalanineNot AvailableNot Available
PheNot AvailableNot Available
PHENYLALANINENot AvailableNot Available
β-phenyl-L-alanineNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number63-91-2
WeightAverage: 165.1891
Monoisotopic: 165.078978601
Chemical FormulaC9H11NO2
InChI KeyCOLNVLDHVKWLRT-QMMMGPOBSA-N
InChI
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
IUPAC Name
(2S)-2-amino-3-phenylpropanoic acid
SMILES
N[C@@H](CC1=CC=CC=C1)C(O)=O
Mass Specshow(8.46 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassPhenylpropanoic Acids
SubclassNot Available
Direct parentPhenylpropanoic Acids
Alternative parentsAlpha Amino Acids and Derivatives; Amphetamines and Derivatives; Amino Fatty Acids; Carboxylic Acids; Enolates; Polyamines; Monoalkylamines
Substituentsbenzene; carboxylic acid; enolate; polyamine; carboxylic acid derivative; amine; primary amine; primary aliphatic amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenylpropanoic acids. These are compounds whose structure contain a benzene ring conjugated to a propanoic acid.
Pharmacology
IndicationL-phenylalanine may be helpful in some with depression. It may also be useful in the treatment of vitiligo. There is some evidence that L-phenylalanine may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic drugs.
PharmacodynamicsUsed by the brain to produce Norepinephrine, a chemical that transmits signals between nerve cells and the brain; keeps you awake and alert; reduces hunger pains; functions as an antidepressant and helps improve memory.
Mechanism of actionThe mechanism of L-phenylalanine's putative antidepressant activity may be accounted for by its precursor role in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
The mechanism of L-phenylalanine's possible antivitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin
AbsorptionAbsorbed from the small intestine by a sodium dependent active transport process.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic. L-phenylalanine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body, where it undergoes metabolic reactions similar to those that take place in the liver.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityL-phenylalanine will exacerbate symptoms of phenylketonuria if used by phenylketonurics. L-phenylalanine was reported to exacerbate tardive dyskinesia when used by some with schizophrenia.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Tyrosinemia Type 2 (or Richner-Hanhart syndrome)DiseaseSMP00369
Tyrosinemia Type 3 (TYRO3)DiseaseSMP00370
Phenylalanine and Tyrosine MetabolismMetabolicSMP00008
PhenylketonuriaDiseaseSMP00206
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9733
Blood Brain Barrier + 0.5902
Caco-2 permeable + 0.8129
P-glycoprotein substrate Non-substrate 0.721
P-glycoprotein inhibitor I Non-inhibitor 0.9916
P-glycoprotein inhibitor II Non-inhibitor 0.9941
Renal organic cation transporter Non-inhibitor 0.9204
CYP450 2C9 substrate Non-substrate 0.8512
CYP450 2D6 substrate Non-substrate 0.8296
CYP450 3A4 substrate Non-substrate 0.8378
CYP450 1A2 substrate Non-inhibitor 0.9448
CYP450 2C9 substrate Non-inhibitor 0.9792
CYP450 2D6 substrate Non-inhibitor 0.9674
CYP450 2C19 substrate Non-inhibitor 0.9797
CYP450 3A4 substrate Non-inhibitor 0.9278
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9896
Ames test Non AMES toxic 0.9211
Carcinogenicity Non-carcinogens 0.8441
Biodegradation Ready biodegradable 0.7562
Rat acute toxicity 1.9053 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9805
hERG inhibition (predictor II) Non-inhibitor 0.9737
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
L-phenylalanine 500 mg tablet0.11USDeach
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point283 dec °CPhysProp
water solubility2.69E+004 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-1.38AVDEEF,A (1997)
pKa1.24 (at 25 °C)KORTUM,G ET AL (1961)
Predicted Properties
PropertyValueSource
water solubility4.14e+00 g/lALOGPS
logP-1.4ALOGPS
logP-1.2ChemAxon
logS-1.6ALOGPS
pKa (strongest acidic)2.47ChemAxon
pKa (strongest basic)9.45ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count2ChemAxon
polar surface area63.32ChemAxon
rotatable bond count3ChemAxon
refractivity45.12ChemAxon
polarizability17.03ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
References
Synthesis Reference

Gerald L. Bachman, “Recovery of L-phenylalanine and L-aspartic acid during preparation of .alpha.-L-aspartyl-L-phenylalanine methyl ester.” U.S. Patent US4348317, issued January, 1967.

US4348317
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00021
KEGG CompoundC00079
PubChem Compound6140
PubChem Substance46505708
ChemSpider5910
ChEBI17295
ChEMBLCHEMBL301523
Therapeutic Targets DatabaseDAP000807
PharmGKBPA450931
IUPHAR3313
Guide to Pharmacology3313
HETPHE
PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/lph_0201.shtml
WikipediaL-Phenylalanine
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSshow(72.5 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Tyrosine aminotransferase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tyrosine aminotransferase P17735 Details

References:

  1. Luong TN, Kirsch JF: A continuous coupled spectrophotometric assay for tyrosine aminotransferase activity with aromatic and other nonpolar amino acids. Anal Biochem. 1997 Nov 1;253(1):46-9. Pubmed
  2. Rege AA: Purification and characterization of a tyrosine aminotransferase from Crithidia fasciculata. Mol Biochem Parasitol. 1987 Aug;25(1):1-9. Pubmed
  3. De-Eknamkul W, Ellis BE: Behavior of Free Aromatic Amino Acid Pools in Rosmarinic Acid-Producing Cell Cultures of Anchusa officinalis L. Plant Physiol. 1989 Feb;89(2):429-433. Pubmed
  4. Patrizio M, Colucci M, Levi G: Human immunodeficiency virus type 1 Tat protein decreases cyclic AMP synthesis in rat microglia cultures. J Neurochem. 2001 Apr;77(2):399-407. Pubmed

2. Large neutral amino acids transporter small subunit 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Large neutral amino acids transporter small subunit 2 Q9UHI5 Details

References:

  1. Shennan DB, Calvert DT, Travers MT, Kudo Y, Boyd CA: A study of L-leucine, L-phenylalanine and L-alanine transport in the perfused rat mammary gland: possible involvement of LAT1 and LAT2. Biochim Biophys Acta. 2002 Aug 19;1564(1):133-9. Pubmed
  2. Rossier G, Meier C, Bauch C, Summa V, Sordat B, Verrey F, Kuhn LC: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine. J Biol Chem. 1999 Dec 3;274(49):34948-54. Pubmed
  3. Babu E, Kanai Y, Chairoungdua A, Kim DK, Iribe Y, Tangtrongsup S, Jutabha P, Li Y, Ahmed N, Sakamoto S, Anzai N, Nagamori S, Endou H: Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters. J Biol Chem. 2003 Oct 31;278(44):43838-45. Epub 2003 Aug 20. Pubmed
  4. Satoh S, Kimura T, Toda M, Maekawa M, Ono S, Narita H, Miyazaki H, Murayama T, Nomura Y: Involvement of L-type-like amino acid transporters in S-nitrosocysteine-stimulated noradrenaline release in the rat hippocampus. J Neurochem. 1997 Nov;69(5):2197-205. Pubmed
  5. Nemoto T, Shimma N, Horie S, Saito T, Okuma Y, Nomura Y, Murayama T: Involvement of the system L amino acid transporter on uptake of S-nitroso-L-cysteine, an endogenous S-nitrosothiol, in PC12 cells. Eur J Pharmacol. 2003 Jan 1;458(1-2):17-24. Pubmed

3. Phenylalanine--tRNA ligase alpha subunit

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Phenylalanine--tRNA ligase alpha subunit Q9Y285 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Kodama K, Fukuzawa S, Sakamoto K, Nakayama H, Kigawa T, Yabuki T, Matsuda N, Shirouzu M, Takio K, Tachibana K, Yokoyama S: A new protein engineering approach combining chemistry and biology, part I; site-specific incorporation of 4-iodo-L-phenylalanine in vitro by using misacylated suppressor tRNAPhe. Chembiochem. 2006 Oct;7(10):1577-81. Pubmed
  4. Kotik-Kogan O, Moor N, Tworowski D, Safro M: Structural basis for discrimination of L-phenylalanine from L-tyrosine by phenylalanyl-tRNA synthetase. Structure. 2005 Dec;13(12):1799-807. Pubmed

4. Phenylalanine-4-hydroxylase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Phenylalanine-4-hydroxylase P00439 Details

References:

  1. Thorolfsson M, Ibarra-Molero B, Fojan P, Petersen SB, Sanchez-Ruiz JM, Martinez A: L-phenylalanine binding and domain organization in human phenylalanine hydroxylase: a differential scanning calorimetry study. Biochemistry. 2002 Jun 18;41(24):7573-85. Pubmed
  2. Pueschel SM, Boylan J, Ellenbogen R: Studies on experimentally induced hyperphenylalaninemia. J Ment Defic Res. 1988 Aug;32 ( Pt 4):309-19. Pubmed
  3. Nagasaki Y, Matsubara Y, Takano H, Fujii K, Senoo M, Akanuma J, Takahashi K, Kure S, Hara M, Kanegae Y, Saito I, Narisawa K: Reversal of hypopigmentation in phenylketonuria mice by adenovirus-mediated gene transfer. Pediatr Res. 1999 Apr;45(4 Pt 1):465-73. Pubmed
  4. Fusetti F, Erlandsen H, Flatmark T, Stevens RC: Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. J Biol Chem. 1998 Jul 3;273(27):16962-7. Pubmed
  5. Stokka AJ, Flatmark T: Substrate-induced conformational transition in human phenylalanine hydroxylase as studied by surface plasmon resonance analyses: the effect of terminal deletions, substrate analogues and phosphorylation. Biochem J. 2003 Feb 1;369(Pt 3):509-18. Pubmed

5. Phenylalanine--tRNA ligase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Phenylalanine--tRNA ligase, mitochondrial O95363 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Kodama K, Fukuzawa S, Sakamoto K, Nakayama H, Kigawa T, Yabuki T, Matsuda N, Shirouzu M, Takio K, Tachibana K, Yokoyama S: A new protein engineering approach combining chemistry and biology, part I; site-specific incorporation of 4-iodo-L-phenylalanine in vitro by using misacylated suppressor tRNAPhe. Chembiochem. 2006 Oct;7(10):1577-81. Pubmed
  4. Kotik-Kogan O, Moor N, Tworowski D, Safro M: Structural basis for discrimination of L-phenylalanine from L-tyrosine by phenylalanyl-tRNA synthetase. Structure. 2005 Dec;13(12):1799-807. Pubmed

6. Phenylalanine--tRNA ligase beta subunit

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Phenylalanine--tRNA ligase beta subunit Q9NSD9 Details

References:

  1. Kotik-Kogan O, Moor N, Tworowski D, Safro M: Structural basis for discrimination of L-phenylalanine from L-tyrosine by phenylalanyl-tRNA synthetase. Structure. 2005 Dec;13(12):1799-807. Pubmed

7. Tyrosine 3-monooxygenase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Tyrosine 3-monooxygenase P07101 Details

References:

  1. Fukami MH, Haavik J, Flatmark T: Phenylalanine as substrate for tyrosine hydroxylase in bovine adrenal chromaffin cells. Biochem J. 1990 Jun 1;268(2):525-8. Pubmed
  2. Ogawa S, Ichinose H: Effect of metals and phenylalanine on the activity of human tryptophan hydroxylase-2: comparison with that on tyrosine hydroxylase activity. Neurosci Lett. 2006 Jul 3;401(3):261-5. Epub 2006 Apr 11. Pubmed
  3. Schallreuter KU, Kothari S, Hasse S, Kauser S, Lindsey NJ, Gibbons NC, Hibberts N, Wood JM: In situ and in vitro evidence for DCoH/HNF-1 alpha transcription of tyrosinase in human skin melanocytes. Biochem Biophys Res Commun. 2003 Feb 7;301(2):610-6. Pubmed
  4. McQuade PS, Juorio AV: The effect of various amino acids and drugs on the para- and meta-hydroxyphenylacetic acid concentrations in the mouse caudate nucleus. Neurochem Res. 1983 Jul;8(7):903-12. Pubmed
  5. Fusetti F, Erlandsen H, Flatmark T, Stevens RC: Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. J Biol Chem. 1998 Jul 3;273(27):16962-7. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Transporters

1. Monocarboxylate transporter 10

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Monocarboxylate transporter 10 Q8TF71 Details

References:

  1. Kim DK, Kanai Y, Matsuo H, Kim JY, Chairoungdua A, Kobayashi Y, Enomoto A, Cha SH, Goya T, Endou H: The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. Genomics. 2002 Jan;79(1):95-103. Pubmed
  2. Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H: Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem. 2001 May 18;276(20):17221-8. Epub 2001 Feb 20. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08