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phenylalanine-4-hydroxylase; phenylalanine-4-monooxygenase (PAH)
Function:
- amino-acid degradation, L-phenylalanine degradation
- acetoacetate & fumarate from L-phenylalanine: step 1/6
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
Cofactor: Fe+2 ion
Structure:
- homodimer
- belongs to the biopterin-dependent aromatic amino acid
- hydroxylase family
- contains 1 ACT domain
- N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine & to constitute an "inhibitory" domain that regulates the activity of a catalytic domain in the C-terminal portion of the enzyme
Pathology:
- defects in PAH are the cause of hyperphenylalaninemia & phenylketonuria
Laboratory:
- PAH gene mutation
Polymorphism:
- Glu-274 variant occurs on approximately 4% of African-American PAH alleles; enzyme activity of this variant is normal
General
hydroxylase; monooxygenase
phosphoprotein
Properties
SIZE: entity length = 452 aa
MW = 52 kD
MOTIF: Ser phosphorylation site {S16}
ACT {35-110}
Iron [Fe]-binding site
SITE: 285-285
Iron [Fe]-binding site
SITE: 290-290
Iron [Fe]-binding site
SITE: 330-330
Database Correlations
OMIM 261600
UniProt P00439
PFAM correlations
KEGG correlations
ENZYME 1.14.16.1
References
- Principles of Biochemistry 6th ed., White, Handler,
Smith, Hill, & Lehman (eds.) McGraw-Hill, NY 1978,
pg 689
- UniProt :accession P00439
- PAHdb; Phenylalanine hydroxylase locus knowledgebase
http://www.pahdb.mcgill.ca/
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=PAH
- Wikipedia; Phenylalanine hydroxylase entry
http://en.wikipedia.org/wiki/Phenylalanine_hydroxylase