GTP cyclohydrolase 1
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 • nucleotide binding • GTP cyclohydrolase I activity • GTP cyclohydrolase I activity • calcium ion binding • protein binding • GTP binding • zinc ion binding • hydrolase activity • GTP-dependent protein binding • protein homodimerization activity • coenzyme binding Cellular component • soluble fraction • nucleus • nucleolus • cytoplasm • cytosol • cytosol • cytoplasmic vesicle • nuclear membrane • protein complex Biological process • GTP catabolic process • protein complex assembly • tetrahydrobiopterin biosynthetic process • tetrahydrobiopterin biosynthetic process • nitric oxide biosynthetic process • induction of apoptosis • regulation of blood pressure • regulation of lung blood pressure • response to lipopolysaccharide • response to lipopolysaccharide • response to interferon-gamma • response to tumor necrosis factor • 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 • positive regulation of nitric-oxide synthase activity • dihydrobiopterin metabolic process • protein homooligomerization • protein heterooligomerization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2643	14528
Ensembl	ENSG00000131979	ENSMUSG00000037580
UniProt	P30793	Q05915
RefSeq (mRNA)	NM_000161.2	NM_008102.3
RefSeq (protein)	NP_000152.1	NP_032128.1
Location (UCSC)	Chr 14: 55.31 – 55.37 Mb	Chr 14: 47.77 – 47.81 Mb
PubMed search	[1]	[2]
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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 3'-triphosphate (7,8-DHNP-3'-TP, 7,8-NH₂-3'-TP).

GTPCH is encoded by the gene GCH1. 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. Mutations in this gene are associated with malignant phenylketonuria (PKU) and hyperphenylalaninemia (HPA), as well as L-DOPA (Levodopa)-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all of the variants give rise to a functional enzyme.^[1]

The chemical reaction performed by GTPCH. The important carbons relative to the transformation are numbered for reference.

See also [link]

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

References [link]

• Voet, Judith G.; Voet, Donald (2004). Biochemistry. New York: J. Wiley & Sons. ISBN 0-471-39223-5. 
• EC 3.5.4.16 IUBMB Enzyme Nomenclature

External links [link]

• 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

v t e PDB gallery 1fb1: CRYSTAL STRUCTURE OF HUMAN GTP CYCLOHYDROLASE I   1is7: Crystal structure of rat GTPCHI/GFRP stimulatory complex   1is8: Crystal structure of rat GTPCHI/GFRP stimulatory complex plus Zn   1wpl: Crystal structure of the inhibitory form of rat GTP cyclohydrolase I/GFRP complex

NB: The numbering of the carbons of the pentose sugar is incorrect. The first carbon is the one attaching the purine and the fifth is the one attaching the phosphate. The image needs correction please.

File:15-11-2011 02-33-12.jpg