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Phenylalanine hydroxylase: Wikis


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Phenylalanine hydroxylase

predicted 3D structure of phenylalanine hydroxylase
Available structures
1dmw, 1j8t, 1j8u, 1kw0, 1lrm, 1mmk, 1mmt, 1pah, 1phz, 1tdw, 1tg2, 2pah, 2phm, 3pah, 4pah, 5pah, 6pah
Symbols PAH; PKU; PKU1
External IDs OMIM261600 MGI97473 HomoloGene234 GeneCards: PAH Gene
RNA expression pattern
PBB GE PAH 205719 s at tn.png
PBB GE PAH 217583 at tn.png
More reference expression data
Species Human Mouse
Entrez 5053 18478
Ensembl ENSG00000171759 ENSMUSG00000020051
UniProt P00439 Q3UEH8
RefSeq (mRNA) NM_000277 NM_008777
RefSeq (protein) NP_000268 NP_032803
Location (UCSC) Chr 12:
101.76 - 101.84 Mb
Chr 10:
86.95 - 87.01 Mb
PubMed search [1] [2]

Phenylalanine hydroxylase (EC is an enzyme which catalyses the reaction responsible for the addition of a hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine:

Phenylalanine hydroxylase is the rate-limiting enzyme of the metabolic pathway which degrades excess phenylalanine.

The other substrates in the reaction are molecular oxygen and tetrahydrobiopterin. Tetrahydrobiopterin is a member of the group of redox biochemicals known as pteridines. PAH is the gene that encodes for phenylalanine hydroxylase.
It was the research on phenylalanine hydroxylase by Seymour Kaufman that led to the discovery of tetrahydrobiopterin as a biological cofactor.[1]


Clinical significance

Mutations in phenylalanine hydroxylase which result in lower activity are the cause of the disease phenylketonuria, or PKU.

Related enzymes

Phenylalanine hydroxylase is closely related to two other enzymes:

The three enzymes are homologous, that is, are thought to have evolved from the same ancient hydroxylase.


Phenylalanine hydroxylase is a tetramer composed of four monomers, that is, composed of 4 identical subunits. Each subunit is in turn composed of three domains, a regulatory domain, a catalytic domain, and a tetramerization domain.

  • The regulatory domain is composed of the approximately 115 amino acids nearest the amino terminal of the subunit.
  • The catalytic domain is composed of the next approximately 300 amino acids, and is responsible for all of the catalytic activity of the enzyme.
  • The tetramerization domain consists of the remaining amino acids and through the formation of a coiled-coil arrangement of amino acids, holds the tetrameric structure of the holoenzyme together with a leucine zipper.

Phenylalanine hydroxylase contains one bound iron atom per subunit which is necessary for catalytic activity.


External links

Further reading

  • Eisensmith RC, Woo SL (1993). "Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene.". Hum. Mutat. 1 (1): 13–23. doi:10.1002/humu.1380010104. PMID 1301187.  
  • Konecki DS, Lichter-Konecki U (1991). "The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations.". Hum. Genet. 87 (4): 377–88. doi:10.1007/BF00197152. PMID 1679029.  
  • Cotton RG (1991). "Heterogeneity of phenylketonuria at the clinical, protein and DNA levels.". J. Inherit. Metab. Dis. 13 (5): 739–50. doi:10.1007/BF01799577. PMID 2246858.  
  • Erlandsen H, Fusetti F, Martinez A, et al. (1998). "Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria.". Nat. Struct. Biol. 4 (12): 995–1000. doi:10.1038/nsb1297-995. PMID 9406548.  
  • Waters PJ, Parniak MA, Nowacki P, Scriver CR (1998). "In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function.". Hum. Mutat. 11 (1): 4–17. doi:10.1002/(SICI)1098-1004(1998)11:1<4::AID-HUMU2>3.0.CO;2-L. PMID 9450897.  
  • Waters PJ (2003). "How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: insights from in vitro expression.". Hum. Mutat. 21 (4): 357–69. doi:10.1002/humu.10197. PMID 12655545.  


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