GTP cyclohydrolase I

GTP cyclohydrolase 1
250px PDB rendering based on 1fb1.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1FB1
Identifiers
Symbols	GCH1 ; DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1; HPABH4B
External IDs	OMIM: 600225 MGI: 95675 HomoloGene: 132 GeneCards: GCH1 Gene
EC number	3.5.4.16
Gene ontology Molecular function • GTP cyclohydrolase I activity • calcium ion binding • protein binding • GTP binding • zinc ion binding • GTP-dependent protein binding • protein homodimerization activity • coenzyme binding Cellular component • nucleus • nucleoplasm • cytoplasm • cytosol • cytoplasmic vesicle • nuclear membrane • protein complex Biological process • tetrahydrobiopterin biosynthetic process • nitric oxide biosynthetic process • regulation of blood pressure • regulation of lung blood pressure • response to lipopolysaccharide • response to interferon-gamma • response to tumor necrosis factor • 7,8-dihydroneopterin 3'-triphosphate biosynthetic process • vasodilation • dopamine biosynthetic process • pteridine-containing compound biosynthetic process • small molecule metabolic process • negative regulation of blood pressure • nitric oxide metabolic process • tetrahydrofolate biosynthetic process • response to pain • neuromuscular process controlling posture • regulation of nitric-oxide synthase activity • positive regulation of nitric-oxide synthase activity • protein homooligomerization • protein heterooligomerization Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE GCH1 204224 s at tn.png
More reference expression data
Orthologs
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: 54.84 – 54.9 Mb	Chr 14: 47.15 – 47.19 Mb
PubMed search	[1]	[2]

GTP cyclohydrolase I (GTPCH) (EC 3.5.4.16) 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).

Gene

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.

Clinical significance

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

Function

File:GTP-cyclohydrolase-reaction.png The chemical reaction performed by GTPCH. The important carbons relative to the transformation are numbered for reference.
Identifiers
EC number	3.5.4.16
CAS number	Template:CAS
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

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

• Guanosine triphosphate (GTP)
• Tetrahydrobiopterin (THB, BH₄)
• Vitamin B₉ (folic acid → folate)

External links

• GTP Cyclohydrolase I at the US National Library of Medicine Medical Subject Headings (MeSH)
• GeneReviews/NCBI/NIH/UW entry on GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia