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L-Phenylalanine hydroxylase

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Target not currently curated in GtoImmuPdb

Target id: 1240

Nomenclature: L-Phenylalanine hydroxylase

Family: Amino acid hydroxylases, Catecholamine turnover

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 452 12q23.2 PAH phenylalanine hydroxylase
Mouse - 453 10 43.64 cM Pah phenylalanine hydroxylase
Rat - 453 7q13 Pah phenylalanine hydroxylase
Previous and Unofficial Names Click here for help
Phenylalanine 4-monooxygenase | PH | phe-4-monooxygenase | phenylalanine-4-hydroxylase
Database Links Click here for help
Alphafold
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 1.14.16.1 L-phenylalanine + O2 -> L-tyrosine
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
L-phenylalanine Substrate is endogenous in the given species N/A - -
Products Click here for help
Product Species Reference
L-tyrosine Product is produced endogenously in the given species Human
Cofactors Click here for help
Cofactor Species Comments Reference
sapropterin Human
Endogenous activators (Rat)
Protein kinase A-mediated phosphorylation  [1]

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
sapropterin Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Activation 5.4 pKi 3
pKi 5.4 (Ki 4x10-6 M) [3]
Description: Binding affinity for human PAH.
Activator Comments
L-Phenylalanine hydroxylase is the probable primary target of the approved activating drug sapropterin.
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
α-methylphenylalanine Small molecule or natural product Rn Inhibition - - 2
[2]
fenclonine Small molecule or natural product Click here for species-specific activity table Hs Inhibition - -
View species-specific inhibitor tables
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Classical phenylketonuria
Synonyms: Phenylketonuria [OMIM: 261600] [Disease Ontology: DOID:9281]
Disease Ontology: DOID:9281
OMIM: 261600
Orphanet: ORPHA79254
Role: 
Drugs: 
Comments: 
References:  4
Disease:  Maternal hyperphenylalaninemia
OMIM: 261600
Orphanet: ORPHA2209
Disease:  Mild hyperphenylalaninemia
OMIM: 261600
Orphanet: ORPHA79651
Drugs: 
Disease:  Mild phenylketonuria
Synonyms: Phenylketonuria [OMIM: 261600] [Disease Ontology: DOID:9281]
Disease Ontology: DOID:9281
OMIM: 261600
Orphanet: ORPHA79253
Drugs: 
Disease:  Tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria
Orphanet: ORPHA293284
Drugs: 

References

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1. Abita JP, Milstien S, Chang N, Kaufman S. (1976) In vitro activation of rat liver phenylalanine hydroxylase by phosphorylation. J Biol Chem, 251 (17): 5310-4. [PMID:182695]

2. Greengard O, Yoss MS, Del Valle JA. (1976) Alpha-methylphenylalanine, a new inducer of chronic hyperphenylalaninemia in sucling rats. Science, 192 (4243): 1007-8. [PMID:944951]

3. Teigen K, Dao KK, McKinney JA, Gorren AC, Mayer B, Frøystein NA, Haavik J, Martínez A. (2004) Tetrahydrobiopterin binding to aromatic amino acid hydroxylases. Ligand recognition and specificity. J Med Chem, 47 (24): 5962-71. [PMID:15537351]

4. Thomas J, Levy H, Amato S, Vockley J, Zori R, Dimmock D, Harding CO, Bilder DA, Weng HH, Olbertz J et al.. (2018) Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM). Mol Genet Metab, 124 (1): 27-38. [PMID:29653686]

How to cite this page

Amino acid hydroxylases: L-Phenylalanine hydroxylase . Last modified on 10/07/2018. Accessed on 23/09/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1240.