L-PHENYLALANINE
Relevant Data
Food Additives Approved by WHO:
Flavouring Substances Approved by European Union:
General Information
| Mainterm | L-PHENYLALANINE |
| Doc Type | ASP |
| CAS Reg.No.(or other ID) | 63-91-2 |
| Regnum |
172.320 |
From www.fda.gov
Computed Descriptors
Download SDF| 2D Structure | |
| CID | 6140 |
| IUPAC Name | (2S)-2-amino-3-phenylpropanoic acid |
| 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 |
| InChI Key | COLNVLDHVKWLRT-QMMMGPOBSA-N |
| Canonical SMILES | C1=CC=C(C=C1)CC(C(=O)O)N |
| Molecular Formula | C9H11NO2 |
| Wikipedia | phenylanine |
From Pubchem
Computed Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 165.192 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 3 |
| Complexity | 153.0 |
| CACTVS Substructure Key Fingerprint | A A A D c c B y M A A A A A A A A A A A A A A A A A A A A A A A A A A w A A A A A A A A A A A B A A A A H g A Q C A A A D C j B m A Q w C I B A A g C I A i D S C A A C A A A g A A A I i I G A A I g K I D K A k R G A Y A A k k A A I i A e Y y K C O A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = = |
| Topological Polar Surface Area | 63.3 |
| Monoisotopic Mass | 165.079 |
| Exact Mass | 165.079 |
| Compound Is Canonicalized | True |
| Formal Charge | 0 |
| Heavy Atom Count | 12 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
From Pubchem
Food Additives Biosynthesis/Degradation
ADMET Predicted Profile --- Classification
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.5902 |
| Human Intestinal Absorption | HIA+ | 0.9733 |
| Caco-2 Permeability | Caco2+ | 0.8129 |
| P-glycoprotein Substrate | Non-substrate | 0.7210 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9916 |
| Non-inhibitor | 0.9941 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9204 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.5948 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8512 |
| CYP450 2D6 Substrate | Non-substrate | 0.8296 |
| CYP450 3A4 Substrate | Non-substrate | 0.8378 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9448 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9792 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9674 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9797 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9278 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9896 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9805 |
| Non-inhibitor | 0.9737 | |
| AMES Toxicity | Non AMES toxic | 0.9211 |
| Carcinogens | Non-carcinogens | 0.8441 |
| Fish Toxicity | High FHMT | 0.7271 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.7243 |
| Honey Bee Toxicity | Low HBT | 0.6582 |
| Biodegradation | Ready biodegradable | 0.7562 |
| Acute Oral Toxicity | III | 0.6736 |
| Carcinogenicity (Three-class) | Non-required | 0.7588 |
From admetSAR
ADMET Predicted Profile --- Regression
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -1.1675 | LogS |
| Caco-2 Permeability | 0.8525 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.9053 | LD50, mol/kg |
| Fish Toxicity | 2.8458 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | -0.7052 | pIGC50, ug/L |
From admetSAR
Toxicity Profile
| Route of Exposure | Absorbed from the small intestine by a sodium dependent active transport process. |
|---|---|
| Mechanism of Toxicity | Extremely high serum levels of phenylalanine are found in patients with the inborn error of metabolism (IEM) called Phenylketonuria (PKU). At pathological concentrations typical of PKU, phenylalanine self-assembles into fibrils with amyloid-like morphology and well-ordered electron diffraction. These fibrils and their resulting amyloid deposits that localize to the brain appear to be partially responsible for the neural tissue damage seen in PKU patients . It has also been suggested that very high plasma phenylalanine concentrations can increase phenylalanine entry into brain and thereby restrict the entry of other large neutral amino acids. The lack of large neutral amino acids may lead to disturbed cerebral protein synthesis, which is particularly important for young children . The 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. <br/>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. |
| 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. |
| Toxicity Values | |
| Lethal Dose | |
| Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
| Minimum Risk Level | |
| Health Effects | Phenylalanine is neurotoxic. Chronic exposure to very high levels of phenylalanine in the blood (as found in phenylketonuria, or PKU) can lead to a build up in the cerebrospinal fluid and brain, leading to seizures, organ damage and unusual posture. High phenylalnine levels are particularly dangerous for children, because it retards brain development and can cause serious learning difficulties. Complications of PKU include severe intellectual disability, brain function abnormalities, microcephaly, mood disorders, irregular motor functioning, and behavioral problems such as attention deficit hyperactivity disorder. Chronically high levels of phenylalanine are associated with at least four other inborn errors of metabolism including: Hartnup Disorder, Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency, Tyrosinemia Type 2 (or Richner-Hanhart syndrome) and Tyrosinemia Type 3 (TYRO3). |
| Treatment | If PKU is diagnosed early, an affected newborn can grow up with normal brain development, but only by managing and controlling phenylalanine levels through diet, or a combination of diet and medication. The diet requires severely restricting or eliminating foods high in phenylalanine, such as meat, chicken, fish, eggs, nuts, cheese, legumes, milk and other dairy products. Starchy foods, such as potatoes, bread, pasta, and corn, must be monitored. Optimal health ranges (or "target ranges") of serum phenylalanine are between 120 and 360 µmol/L, and aimed to be achieved during at least the first 10 years of life. Recently it has been found that a chiral isomer of L-phenylalanine (called D-phenylalanine) actually arrests the fibril formation by L-phenylalanine and gives rise to flakes. These flakes do not propagate further and prevent amyloid formation by L-phenylalanine. D-phenylalanine may qualify as a therapeutic molecule in phenylketonuria . |
| Reference |
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From T3DB
Taxonomic Classification
| Kingdom | Organic compounds |
|---|---|
| Superclass | Organic acids and derivatives |
| Class | Carboxylic acids and derivatives |
| Subclass | Amino acids, peptides, and analogues |
| Intermediate Tree Nodes | Amino acids and derivatives - Alpha amino acids and derivatives |
| Direct Parent | Phenylalanine and derivatives |
| Alternative Parents | |
| Molecular Framework | Aromatic homomonocyclic compounds |
| Substituents | Phenylalanine or derivatives - 3-phenylpropanoic-acid - Alpha-amino acid - Amphetamine or derivatives - L-alpha-amino acid - Aralkylamine - Monocyclic benzene moiety - Benzenoid - Amino acid - Carboxylic acid - Monocarboxylic acid or derivatives - Organic nitrogen compound - Primary amine - Organooxygen compound - Organonitrogen compound - Hydrocarbon derivative - Primary aliphatic amine - Organic oxide - Carbonyl group - Organopnictogen compound - Organic oxygen compound - Amine - Aromatic homomonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom. |
From ClassyFire
Targets
- General Function:
- Toxin transporter activity
- Specific Function:
- Sodium-independent, high-affinity transport of small and large neutral amino acids such as alanine, serine, threonine, cysteine, phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Acts as an amino acid exchanger. Has higher affinity for L-phenylalanine than LAT1 but lower affinity for glutamine and serine. L-alanine is transported at physiological concentrations. Plays a role in basolateral (re)absorption of neutral amino acids. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. Plays an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney.
- Gene Name:
- SLC7A8
- Uniprot ID:
- Q9UHI5
- Molecular Weight:
- 58381.12 Da
References
- 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. [12498902 ]
- General Function:
- Phenylalanine 4-monooxygenase activity
- Gene Name:
- PAH
- Uniprot ID:
- P00439
- Molecular Weight:
- 51861.565 Da
References
- 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. [12379147 ]
- General Function:
- Trna binding
- Gene Name:
- FARSA
- Uniprot ID:
- Q9Y285
- Molecular Weight:
- 57563.225 Da
References
- 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. [16338408 ]
- General Function:
- Trna binding
- Specific Function:
- Is responsible for the charging of tRNA(Phe) with phenylalanine in mitochondrial translation. To a lesser extent, also catalyzes direct attachment of m-Tyr (an oxidized version of Phe) to tRNA(Phe), thereby opening the way for delivery of the misacylated tRNA to the ribosome and incorporation of ROS-damaged amino acid into proteins.
- Gene Name:
- FARS2
- Uniprot ID:
- O95363
- Molecular Weight:
- 52356.21 Da
References
- 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. [16338408 ]
- General Function:
- Rna binding
- Gene Name:
- FARSB
- Uniprot ID:
- Q9NSD9
- Molecular Weight:
- 66114.93 Da
References
- 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. [16338408 ]
- General Function:
- Tyrosine 3-monooxygenase activity
- Specific Function:
- Plays an important role in the physiology of adrenergic neurons.
- Gene Name:
- TH
- Uniprot ID:
- P07101
- Molecular Weight:
- 58599.545 Da
References
- 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. [6621777 ]
- General Function:
- Pyridoxal phosphate binding
- Specific Function:
- Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine.
- Gene Name:
- TAT
- Uniprot ID:
- P17735
- Molecular Weight:
- 50398.895 Da
References
- 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. [11299302 ]
- General Function:
- Pyrophosphatase activity
- Specific Function:
- This isozyme may play a role in skeletal mineralization.
- Gene Name:
- ALPL
- Uniprot ID:
- P05186
- Molecular Weight:
- 57304.435 Da
References
- Lanier M, Sergienko E, Simao AM, Su Y, Chung T, Millan JL, Cashman JR: Design and synthesis of selective inhibitors of placental alkaline phosphatase. Bioorg Med Chem. 2010 Jan 15;18(2):573-9. doi: 10.1016/j.bmc.2009.12.012. Epub 2009 Dec 11. [20031422 ]
- General Function:
- Zinc ion binding
- Gene Name:
- ALPI
- Uniprot ID:
- P09923
- Molecular Weight:
- 56811.695 Da
References
- Lanier M, Sergienko E, Simao AM, Su Y, Chung T, Millan JL, Cashman JR: Design and synthesis of selective inhibitors of placental alkaline phosphatase. Bioorg Med Chem. 2010 Jan 15;18(2):573-9. doi: 10.1016/j.bmc.2009.12.012. Epub 2009 Dec 11. [20031422 ]
- General Function:
- Phospholipase a2 activator activity
- Specific Function:
- Involved in the maintenance of ubiquitin levels.
- Gene Name:
- PLAA
- Uniprot ID:
- Q9Y263
- Molecular Weight:
- 87156.21 Da
References
- Lanier M, Sergienko E, Simao AM, Su Y, Chung T, Millan JL, Cashman JR: Design and synthesis of selective inhibitors of placental alkaline phosphatase. Bioorg Med Chem. 2010 Jan 15;18(2):573-9. doi: 10.1016/j.bmc.2009.12.012. Epub 2009 Dec 11. [20031422 ]
From T3DB