GTP cyclohydrolase (GTP cyclohydrolase 1, GTP dihydrolase, GTP ring-opening enzyme, GTP 8-formylhydrolase, GCH1)

Introduction

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

More general terms

• aminohydrolase (deaminase)
• phosphoprotein

Additional terms

• GTP cyclohydrolase 1 feedback regulatory protein; GFRP; GTP cyclohydrolase I feedback regulatory protein; p35 (GCHFR, GFRP)
• GTP cyclohydrolase deficiency

Database

• UniProt: http://www.uniprot.org/uniprot/P30793.html
• OMIM: https://mirror.omim.org/entry/600225
• OMIM: https://mirror.omim.org/entry/128230
• OMIM: https://mirror.omim.org/entry/233910
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2643