GTPCH is encoded by the geneGCH1. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all of the variants give rise to a functional enzyme.[5]
^Šimčíková D, Heneberg P (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports. 9 (1): 18577. Bibcode:2019NatSR...918577S. doi:10.1038/s41598-019-54976-4. PMC6901466. PMID 31819097.
^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. S2CID 13117236.
cyclohydrolase, gtpch, member, cyclohydrolase, family, enzymes, gtpch, part, folate, biopterin, biosynthesis, pathways, responsible, hydrolysis, guanosine, triphosphate, form, dihydroneopterin, triphosphate, dhnp, gch1available, structurespdbortholog, search, . 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 GCH1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1FB1IdentifiersAliasesGCH1 DYT14 DYT5 DYT5a GCH GTP CH 1 GTPCH1 HPABH4B GTP cyclohydrolase 1External IDsOMIM 600225 MGI 95675 HomoloGene 132 GeneCards GCH1Gene location Human Chr Chromosome 14 human 1 Band14q22 2Start54 842 008 bp 1 End54 902 826 bp 1 Gene location Mouse Chr Chromosome 14 mouse 2 Band14 C1 14 24 6 cMStart47 391 352 bp 2 End47 426 870 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed insecondary oocytejejunal mucosakidney tubulepalpebral conjunctivamonocyteright lobe of liverglomerulusmetanephric glomerulusretinal pigment epitheliumduodenumTop expressed insuperior cervical ganglionpineal glandleft lobe of liverislet of Langerhanspyloric antrumsecondary oocytecumulus cellmucous cell of stomachadrenal glandileumMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionnucleotide binding calcium ion binding protein homodimerization activity zinc ion binding GTP binding metal ion binding protein binding catalytic activity hydrolase activity GTP cyclohydrolase I activity mitogen activated protein kinase binding GTPase activity GTP dependent protein binding translation initiation factor bindingCellular componentcytoplasm cytosol nuclear membrane nucleoplasm cytoplasmic vesicle nucleus neuron projection terminus protein containing complexBiological processnitric oxide biosynthetic process response to interferon gamma neuromuscular process controlling posture protein heterooligomerization negative regulation of blood pressure dopamine biosynthetic process regulation of lung blood pressure vasodilation pteridine containing compound biosynthetic process 7 8 dihydroneopterin 3 triphosphate biosynthetic process dihydrobiopterin metabolic process regulation of blood pressure response to tumor necrosis factor tetrahydrofolate biosynthetic process response to lipopolysaccharide positive regulation of nitric oxide synthase activity response to pain tetrahydrobiopterin biosynthetic process metabolism protein homooligomerization regulation of removal of superoxide radicals positive regulation of heart rate protein containing complex assemblySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez264314528EnsemblENSG00000131979ENSMUSG00000037580UniProtP30793Q05915RefSeq mRNA NM 000161NM 001024024NM 001024070NM 001024071NM 008102RefSeq protein NP 000152NP 001019195NP 001019241NP 001019242NP 032128Location UCSC Chr 14 54 84 54 9 MbChr 14 47 39 47 43 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Gene 2 Clinical significance 3 Function 4 See also 5 References 6 Further reading 7 External linksGene editGTPCH 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 editAt least 94 disease causing mutations in this gene have been discovered 6 Mutations in this gene are associated with two disorders autosomal recessive GTP cyclohydrolase I deficiency and autosomal dominant GTP cyclohydrolase I deficiency These may present with malignant phenylketonuria PKU and hyperphenylalaninemia HPA 5 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 7 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 8 Function edit nbsp The chemical reaction performed by GTPCH The important carbons relative to the transformation are numbered for reference IdentifiersEC no 3 5 4 16CAS no 37289 19 3DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteins 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 citation needed GTPCH GCH1 and tetrahydrobiopterin were found to protect against cell death by ferroptosis Tetrahydrobiopterin BH4 acts as a potent diffusable antioxidant that resists oxidative stress and enables cancer cell survival 9 See also editGuanosine triphosphate GTP Tetrahydrobiopterin THB BH4 Vitamin B9 folic acid folate References edit a b c GRCh38 Ensembl release 89 ENSG00000131979 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000037580 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Entrez Gene GCH1 GTP Cyclohydrolase 1 DOPA Responsive Dystonia Simcikova D Heneberg P December 2019 Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases Scientific Reports 9 1 18577 Bibcode 2019NatSR 918577S doi 10 1038 s41598 019 54976 4 PMC 6901466 PMID 31819097 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 S2CID 13117236 Patient registry Kraft VA Bezjian CT Pfeiffer S Ringelstetter L Muller C Zandkarimi F Merl Pham J Bao X Anastasov N Kossl J Brandner S Daniels JD Schmitt Kopplin P Hauck SM Stockwell BR Hadian K Schick JA January 2020 GTP Cyclohydrolase 1 Tetrahydrobiopterin Counteract Ferroptosis through Lipid Remodeling ACS Central Science 6 1 41 53 doi 10 1021 acscentsci 9b01063 PMC 6978838 PMID 31989025 Further reading editVoet JG Voet D 2004 Biochemistry New York J Wiley amp Sons ISBN 0 471 39223 5 External links editGTP Cyclohydrolase I at the U S National Library of Medicine Medical Subject Headings MeSH GeneReviews NCBI NIH UW entry on GTP Cyclohydrolase 1 Deficient Dopa Responsive Dystonia Overview of all the structural information available in the PDB for UniProt P30793 Human GTP cyclohydrolase 1 at the PDBe KB Portal nbsp Biology Retrieved from https en wikipedia org w index php title GTP cyclohydrolase I amp oldid 1199436609, wikipedia, wiki, book, books, library,
