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GTP cyclohydrolase (GTP cyclohydrolase 1, GTP dihydrolase, GTP ring-opening enzyme, GTP 8-formylhydrolase, GCH1)
May be multiple subtypes.
Function:
- isoform GCH-1 is the functional enzyme
- catalyzes conversion of GTP to D-erythro-7,8-dihydroneopterin triphosphate (first & rate- limiting step in tetrahydrobiopterin biosynthesis)
- function of enzymatically inactive isoforms unknown
- GTP shows a positive allosteric effect
- cofactor biosynthesis, tetrahydrofolate biosynthesis
- 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate from GTP, step 1/5
- phosphorylated
GTP + H2O formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)
-dihydropteridine triphosphate
Inhibition:
- tetrahydrobiopterin inhibits the enzyme activity
Pathology:
- defects in GCH1 associated with:
- GTP cyclohydrolase deficiency
- dopa responsive dystonia
- atypical severe phenylketonuria
Genetics:
- Gene locus: 14q22.1-q22.2
Related
GTP cyclohydrolase 1 feedback regulatory protein; GFRP; GTP cyclohydrolase I feedback regulatory protein; p35 (GCHFR, GFRP)
GTP cyclohydrolase deficiency
General
aminohydrolase (deaminase)
phosphoprotein
Properties
SIZE: entity length = 190-250 aa
MOTIF: active site
phosphorylation site
Database Correlations
OMIM correlations
MORBIDMAP 600225
UniProt P30793
Entrez Gene 2643
Kegg hsa/hsa00790
ENZYME 3.5.4.16
References
- OMIM :accession 600225
- UniProt :accession P30793
- BIOMDB, Db of mutations causing tetrahydrobiopterin deficiencies
http://www.bh4.org/biodef1.html
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=GCH1