Phenylalanine Hydroxylase (PAH, PH)

PAH (phenylalanine hydroxylase), also known as PH, belongs to the biopterin-dependent aromatic amino acid hydroxylase family. It contains 1 ACT domain, N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule. In humans, PAH is expressed both in the liver and the kidney, and there is some indication that it may be differentially regulated in these tissues. PAH catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. It is one of three members of the pterin-dependent amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin and a non-heme iron for catalysis. Defects in PAH are the cause of phenylketonuria (PKU). PKU is an autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol.

Phenylalanine Hydroxylase (PAH, PH) Related Areas

Enzyme>> PAH

Phenylalanine Hydroxylase (PAH, PH) Alternative Names

PH, PKU, PKU1, phe-4-monooxygenase, phenylalanine 4-monooxygenase, phenylalanine-4-hydroxylase [Homo sapiens]

phe-4-monooxygenase, phenylalanine-4-hydroxylase [Mus musculus]

Summaries for Phenylalanine Hydroxylase (PAH, PH)

Entrez Gene summary for Phenylalanine Hydroxylase (PAH, PH):

PAH encodes the enzyme phenylalanine hydroxylase that is the rate-limiting step in phenylalanine catabolism. Deficiency of this enzyme activity results in the autosomal recessive disorder phenylketonuria.

OMIM - description for Phenylalanine Hydroxylase (PAH, PH):

Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism resulting from a deficiency of phenylalanine hydroxylase (PAH; 612349), an enzyme that catalyzes the hydroxylation of phenylalanine to tyrosine, the rate-limiting step in phenylalanine catabolism. If undiagnosed and untreated, phenylketonuria can result in impaired postnatal cognitive development resulting from a neurotoxic effect of hyperphenylalaninemia (Zurfluh et al., 2008).

Wikipedia summary for Phenylalanine Hydroxylase (PAH, PH):

Phenylalanine hydroxylase (PheOH, alternatively PheH or PAH) (EC 1.14.16.1) is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PheOH is one of three members of the pterin-dependent amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin (BH4, a pteridine cofactor) and a non-heme iron for catalysis. During the reaction, molecular oxygen is heterolytically cleaved with sequential incorporation of one oxygen atom into BH4 and phenylalanine substrate

Human Phenylalanine Hydroxylase (PAH, PH) Protein General Information

 

• Protein names: Recommended name: Phenylalanine-4-hydroxylase Short name=PAH
• Sequence length: 452 AA.
• Sequence similarities: Belongs to the biopterin-dependent aromatic amino acid hydroxylase family. Contains 1 ACT domain.
• Polymorphism: The Glu-274 variant occurs on approximately 4% of African-American PAH alleles. The enzyme activity of the variant protein is indistinguishable from that of the wild-type form.
• Subunit structure: Homodimer and homotetramer
• Enzyme regulation: N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an "inhibitory" domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule
• Involvement in disease: Defects in PAH are the cause of phenylketonuria (PKU) [MIM:261600]. PKU is an autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes mental retardation (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor.

General information above from UniProt

Function for Phenylalanine Hydroxylase (PAH, PH) Protein

UniProtKB:

PAH (phenylalanine hydroxylase), also known as PH, belongs to the biopterin-dependent aromatic amino acid hydroxylase family. It contains 1 ACT domain, N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an "inhibitory" domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule. In humans, PAH is expressed both in the liver and the kidney, and there is some indication that it may be differentially regulated in these tissues. PAH catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. It is one of three members of the pterin-dependent amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin and a non-heme iron for catalysis. Defects in PAH are the cause of phenylketonuria (PKU). PKU is an autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol.

Genatlas:

• phenylalanine hydroxylase, iron containing enzyme
• Phenylalanine Hydroxylase (PAH, PH) is rate-limiting step in phenylalanine catabolism
• liver-specific phenylalanine hydroxylase catalyzes the conversion of phenylalanine to tyrosine

Homology for human Phenylalanine Hydroxylase (PAH, PH)

• homolog to murine Pah

Phenotype Information for Phenylalanine Hydroxylase (PAH, PH)

• Gene/Locus: PAH, PKU1
• Phenotype: Phenylketonuria [Hyperphenylalaninemia, non-PKU mild]

Phenotype Information for Phenylalanine Hydroxylase (PAH, PH) from OMIM (Online Mendelian Inheritance in Man)