GTP cyclohydrolase I

From Wikipedia, the free encyclopedia
  (Redirected from GTP cyclohydrolase)
Jump to navigation Jump to search
GCH1
Protein GCH1 PDB 1fb1.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGCH1, DYT14, DYT5, DYT5a, GCH, GTP-CH-1, GTPCH1, HPABH4B, GTP cyclohydrolase 1
External IDsMGI: 95675 HomoloGene: 132 GeneCards: GCH1
Gene location (Human)
Chromosome 14 (human)
Chr.Chromosome 14 (human)[1]
Chromosome 14 (human)
Genomic location for GCH1
Genomic location for GCH1
Band14q22.2Start54,842,008 bp[1]
End54,902,826 bp[1]
RNA expression pattern
PBB GE GCH1 204224 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000161
NM_001024024
NM_001024070
NM_001024071

NM_008102

RefSeq (protein)

NP_000152
NP_001019195
NP_001019241
NP_001019242

NP_032128

Location (UCSC)Chr 14: 54.84 – 54.9 MbChr 14: 47.15 – 47.19 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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[edit]

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.[5]

Clinical significance[edit]

Mutations in this gene are associated with malignant phenylketonuria (PKU) and hyperphenylalaninemia (HPA), as well as GTP cyclohydrolase I deficiency.[5] Deficiency of GTP cyclohydrolase I can occur in a recessive and in a dominant form and lead to a lack of certain neurotransmitters (dopamine, norepinephrine, epinephrine and serotonin). The dominant form, with mutation in only one of the two alleles for GTP cyclohydrolase I, causes dopamine-responsive dystonia, characterized by childhood-onset dystonia. Patients with the recessive form have mutations in both alleles for GTP cyclohydrolase I. Patients present with developmental delays and neurological dysfunction with trunk hypotonia, hypertonia of the extremities, abnormal movements, tremors, convulsions, and sometimes autonomic dysfunction.[6] Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).[7]

Function[edit]

GTP-cyclohydrolase-reaction.png
The chemical reaction performed by GTPCH. The important carbons relative to the transformation are numbered for reference.
Identifiers
EC number3.5.4.16
CAS number37289-19-3
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

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]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000131979 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037580 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ a b "Entrez Gene: GCH1 GTP Cyclohydrolase 1 (DOPA-Responsive Dystonia)".
  6. ^ Longo N (June 2009). "Disorders of biopterin metabolism". Journal of Inherited Metabolic Disease. 32 (3): 333–42. doi:10.1007/s10545-009-1067-2. PMID 19234759.
  7. ^ "Patient registry".

Further reading[edit]

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

External links[edit]