GTP cyclohydrolase I

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GTP cyclohydrolase 1
Protein GCH1 PDB 1fb1.png
PDB rendering based on 1fb1.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols GCH1 ; DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1; HPABH4B
External IDs OMIM600225 MGI95675 HomoloGene132 GeneCards: GCH1 Gene
EC number
RNA expression pattern
PBB GE GCH1 204224 s at tn.png
More reference expression data
Species Human Mouse
Entrez 2643 14528
Ensembl ENSG00000131979 ENSMUSG00000037580
UniProt P30793 Q05915
RefSeq (mRNA) NM_000161 NM_008102
RefSeq (protein) NP_000152 NP_032128
Location (UCSC) Chr 14:
55.31 – 55.37 Mb
Chr 14:
47.15 – 47.19 Mb
PubMed search [1] [2]

GTP cyclohydrolase I (GTPCH) (EC is a member of the GTP cyclohydrolase family of enzymes. GTPCH is part of the folate and biopterin biosynthesis pathways. It is responsible for the hydrolysis of guanosine triphosphate (GTP) to form 7,8-dihydroneopterin triphosphate (7,8-DHNP-3'-TP, 7,8-NH2-3'-TP).


GTPCH is encoded by the gene GCH1. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all of the variants give rise to a functional enzyme.[1]

Clinical significance[edit]

Mutations in this gene are associated with malignant phenylketonuria (PKU) and hyperphenylalaninemia (HPA), as well as L-DOPA (Levodopa)-responsive dystonia.[1]


The chemical reaction performed by GTPCH. The important carbons relative to the transformation are numbered for reference.
EC number
CAS number 37289-19-3
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

The transcribed protein is the first and rate-limiting enzyme in tetrahydrobiopterin (THB, BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-DHNP-3'-TP. THB is an essential cofactor required by the aromatic amino acid hydroxylase (AAAH) and nitric oxide synthase (NOS) enzymes in the biosynthesis of the monoamine neurotransmitters serotonin (5-hydroxytryptamine (5-HT)), melatonin, dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), and nitric oxide (NO), respectively.

See also[edit]


Further reading[edit]

  • Voet, Judith G.; Voet, Donald (2004). Biochemistry. New York: J. Wiley & Sons. ISBN 0-471-39223-5. 

External links[edit]