PMID 17363416 ] Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase 1 gene (GCH1) through the use of 3 or fewer single nucleotide polymorphisms. (snpedia.com)
GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. (qmul.ac.uk)
Conclusions We propose that this GCH1 variant is pathogenic in this family and these findings suggest that similar mechanisms involving abnormal GTP cyclohydolase I may underlie both PD and DRD. (birmingham.ac.uk)
GTPCH3
We have now investigated the importance and mechanisms of BH4 availability in vivo using a novel transgenic mouse model with endothelial-targeted overexpression of the rate-limiting enzyme in BH4 synthesis, guanosine triphosphate-cyclohydrolase I (GTPCH). (ox.ac.uk)
Tetrahydrobiopterin (BH(4)) deficiencies are a highly heterogeneous group of disorders with several hundred patients, and so far a total of 193 different mutant alleles or molecular lesions identified in the GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin synthase (PTPS), sepiapterin reductase (SR), carbinolamine-4a-dehydratase (PCD), or dihydropteridine reductase (DHPR) genes. (qxmd.com)
GTP cyclohydrolase (GTPCH) expression for tetrahydrobiopterin synthesis in tumor stroma is implicated in angiogenesis and tumor development. (oncotarget.com)
Tetrahydrobiopterin4
The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. (origene.com)
Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression. (ox.ac.uk)
Variously substituted 7-deazaguanines are of interest as inhibitors of GTP cyclohydrolase I, the first enzyme in the biosynthetic pathway leading to dihydrofolate and tetrahydrobiopterin. (strath.ac.uk)
Glucocorticoids have been shown to inhibit expression of the rate-limiting enzyme for tetrahydrobiopterin synthesis, GTP cyclohydrolase, in other cell types. (elsevierpure.com)
While Hermann Oppenheim probably described the first cases of genetic (DYT1) dystonia in 1911, the 'modern history' of dystonia genetics dates back to 1994 when mutations in the GTP cyclohydrolase I gene were discovered to cause dopa-responsive dystonia. (uni-luebeck.de)
Ichinose H, Ohye T, Takahashi E, Seki N, Hori T, Segawa M. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. (medscape.com)
ENZYME1
IDO induction has been correlated with induction of GTP-cyclohydrolase, the key enzyme in pteridine biosynthesis. (nih.gov)
With regard to BH4 deficiencies, more than 190 different mutant alleles or molecular lesions have been identified, including in the genes for guanosine triphosphate cyclohydrolase (GCH), 6-pyruvoyl-tetrahydropterin synthase (PTPS), sepiapterin reductase (SR), carbinolamine-4a-dehydratase (PCD), and dihydropteridine reductase (DHPR). (medscape.com)
Synthesis1
We conclude that inhibition of BH 4 synthesis by glucocorticoid regulation of GTP cyclohydrolase expression may contribute to reduced endothelium-dependent vasodilation characteristic of glucocorticoid-induced hypertension. (elsevierpure.com)
Sepiapterin reductase1
Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. (qxmd.com)
Genes2
Copy number variations (CNVs) of the Plasmodium falciparum multidrug resistance 1 ( pfmdr1 ), P. falciparum pfplasmepsin2 ( pfplasmepsin2 ) and P. falciparum GTP cyclohydrolase 1 ( pfgch1 ) genes are associated with antimalarial drug resistance in P. falciparum malaria. (researchsquare.com)
Moreover, amplification of the P . falciparum GTP cyclohydrolase 1 ( pfgch1 ) GCN is linked to upregulation of the Plasmodium falciparum dihydrofolate reductase ( pfdhfr ) and P . falciparum dihydropteroate synthase ( pfdhps ) genes, which are associated with sulfadoxine-pyrimethamine resistance in Southeast Asia [ 9 , 10 ]. (researchsquare.com)
Endothelial function1
Further, we hypothesized that treatment of rat vascular segments with dexamethasone would result in attenuation of endothelial function accompanied by decreased GTP cyclohydrolase expression. (elsevierpure.com)
Triphosphate1
GTP cyclohydrolase I catalyses the complex reaction which converts GTP to dihydroneopterin triphosphate. (ebi.ac.uk)
Imidazole1
GTP cyclohydrolase I contains an essential zinc cation, thought to act as a Lewis acid, activating a water molecule towards hydrolytic opening of the imidazole ring of GTP. (ebi.ac.uk)
Expression1
Dexamethasone incubation abolishes contraction to N ω -nitro-L-arginine (L-NNA, 10 -5 M) in endothelium-intact aortic rings, and inhibits expression of GTP cyclohydrolase. (elsevierpure.com)
Biosynthesis3
GTP cyclohydrolase I catalyzes the first step in folic acid biosynthesis in bacteria and plants, biopterin biosynthesis in mammals, and the biosynthesis of 7-deazaguanosine modified tRNA nucleosides in bacteria and archaea. (pdx.edu)
GCYH-IB is structurally distinct from the canonical type IA GTP cyclohydrolase involved in biopterin biosynthesis in humans and animals, and thus is of interest as a potential antibacterial drug target. (pdx.edu)
magadii contained three genes en coding putative enzymes from the later on phases from the fol ate biosynthesis pathway. (cgrpreceptor.com)
Synthase3
Thony B, Blau N. Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. (medscape.com)
magadii also contained genes encoding a dihydroptero ate synthase, a fused dihydropteroate dihydrofolate synthase, a dihydrofolate reductase, and a methenyltetra hydrofolate cyclohydrolase. (cgrpreceptor.com)
In human umbilical vein endothelial cells, exendin-4 significantly increases NO production, endothelial NO synthase (eNOS) phosphorylation, and GTP cyclohydrolase 1 (GTPCH1) level in a dose-dependent manner [2] . (medchemexpress.com)
Metabolic flux modeling identified further active enzymes such as alcohol dehydrogenase, inositol oxygenase and GTP cyclohydrolase participating in different stress responses in A. fumigatus. (hki-jena.de)
This is the first step in the synthesis of folic acid from GTP. (nih.gov)
Inhibitor3
The GTP cyclohydrolase inhibitor used in this study, DAHP, is not very strong and is unlikely to be useful as a human drug, Woolf says. (nih.gov)
Researchers are now looking for other substances that might work as GTP cyclohydrolase inhibitor drugs in humans. (nih.gov)
one in complex with the reaction intermediate analog and competitive inhibitor 8-oxo-GTP, and one with a TRIS molecule bound in the active site and mimicking another reaction intermediate. (pdx.edu)
GTPCH11
GTP cyclohydrolase 1-deficient dopa-responsive dystonia (GTPCH1-deficient DRD) is characterized by childhood-onset dystonia and a dramatic and sustained response to low doses of oral administration of levodopa. (nih.gov)
13. Validating the GTP-cyclohydrolase 1-feedback regulatory complex as a therapeutic target using biophysical and in vivo approaches. (nih.gov)
Growth4
1. Inhibition of GTP cyclohydrolase attenuates tumor growth by reducing angiogenesis and M2-like polarization of tumor associated macrophages. (nih.gov)
3. Paracrine effect of GTP cyclohydrolase and angiopoietin-1 interaction in stromal fibroblasts on tumor Tie2 activation and breast cancer growth. (nih.gov)
4. Reactive species balance via GTP cyclohydrolase I regulates glioblastoma growth and tumor initiating cell maintenance. (nih.gov)
10. Evolving role of GTP cyclohydrolase 1 inhibition in mitigating cancer pain besides its role in attenuating tumor growth. (nih.gov)