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malfunction
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decreases in GTPCH activity and expression in late stages of acute cardiac rejection due to a deficit in BH4
malfunction
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decreases in GTPCH activity and expression in late stages of acute cardiac rejection due to a deficit in BH4. Mechanism of the decreased rejection appears related to decreased T cell proliferation and modulation of immune function by higher expression of genes involved in hematopoietic/stromal cell development and recruitment
malfunction
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multimeric assemblies of wild-type GTPCH and truncation mutant DELTA45-GTPCH on their own display markedly different banding patterns
malfunction
three different heterozygous mutations in the Punch gene enhance the gmr-Dube3a rough eye phenotype causing a glazed appearance, loss of inter-ommatidial bristles and often displaying yellowish discoloration indicative of underlying neurodegeneration. In the heterozygous state these mutations in Punch show no eye phenotype when crossed to the gmr-GAL4 driver alone and the individual UAS-Dube3a stocks without gmr-GAL4 do not have rough eyes
malfunction
three different heterozygous mutations in the Punch gene enhance the gmr>Dube3a rough eye phenotype causing a glazed appearance, loss of inter-ommatidial bristles and often displaying yellowish discoloration indicative of underlying neurodegeneration. In the heterozygous state these mutations in Punch show no eye phenotype when crossed to the gmr-GAL4 driver alone and the individual UAS-Dube3a stocks without gmr-GAL4 do not have rough eyes
malfunction
GTP cyclohydrolase I gene polymorphisms are associated with endothelial dysfunction and oxidative stress in patients with type 2 diabetes mellitus
malfunction
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decreases in GTPCH activity and expression in late stages of acute cardiac rejection due to a deficit in BH4
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metabolism
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GCH-1 is the rate-limiting enzyme for tetrahydrobiopterin synthesis
metabolism
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GTP cyclohydrolase I is the rate-limiting enzyme in generation of tetrahydrobiopterin
metabolism
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GTPCH I is the rate-limiting enzyme for de novo tetrahydrobiopterin synthesis
metabolism
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GCH1 is the rate-limiting enzyme in the generation of BH4
metabolism
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GTP cyclohydrolase I is the rate-limiting enzyme for tetrahydrobiopterin synthesis
metabolism
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GTP cyclohydrolase I is the rate-limiting enzyme for tetrahydrobiopterin synthesis
metabolism
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GTP cyclohydrolase I, GTPCH-1, is the rate-limiting enzyme involved in de novo biosynthesis of tetrahydrobiopterin, an essential cofactor for nitric oxide synthases and aromatic amino acid hydroxylases
metabolism
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the N-terminal peptide of mammalian GTP cyclohydrolase I is an autoinhibitory control element and contributes to binding the allosteric regulatory protein GFRP
metabolism
the Punch protein, an enzyme that produces tetrahydrobiopterin, is the rate-limiting co-factor in monoamine synthesis. Dube3a, the fly UBE3A orthologue, regulates Punch/GCH1 in the fly brain. Drosophila Ube3a regulates monoamine synthesis by increasing GTP cyclohydrolase I activity via a non-ubiquitin ligase mechanism, overview
metabolism
the Punch protein, an enzyme that produces tetrahydrobiopterin, is the rate-limiting cofactor in monoamine synthesis. Dube3a, the fly UBE3A orthologue, regulates Punch/GCH1 in the fly brain. Drosophila Ube3a regulates monoamine synthesis by increasing GTP cyclohydrolase I activity via a non-ubiquitin ligase mechanism, overview
metabolism
cardiac GTP cyclohydrolase 1 is degraded in remodeled hearts after myocardial infarction, concomitant with increases in the thickness of interventricular septum, interstitial fibrosis, and phosphorylated p38 mitogen-activated protein kinase and decreases in left ventricular anterior wall thickness, cardiac contractility, tetrahydrobiopterin, the dimers of nitric oxide synthase, sarcoplasmic reticulum Ca2+ release, and the expression of sarcoplasmic reticulum Ca2+ handling proteins. Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes reduces the thickness of interventricular septum and interstitial fibrosis and increases anterior wall thickness and cardiac contractility after infarction. Overexpression of GTP cyclohydrolase 1 decreases phosphorylated p38 mitogen-activated protein kinase and elevates tetrahydrobiopterin levels, the dimerization and phosphorylation of neuronal nitric oxide synthase, sarcoplasmic reticulum Ca2+ release, and sarcoplasmic reticulum Ca2+ handling proteins in post-infarction remodeled hearts
metabolism
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GTP cyclohydrolase I is the rate-limiting enzyme for tetrahydrobiopterin synthesis
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physiological function
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endothelium-specific GTP cyclohydrolase I overexpression accelerates refractory wound healing in streptozotocin-induced type 1 diabetic mice through enhanced constitutive NOS activity and suppressed oxidative stress
physiological function
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GCH-1 is a key enzyme in de novo tetrahydrobiopterin biosynthesis. GCH-1 is critical for maintaining coupled NOS activity and aromatic amino acid hydroxylation, pain sensitivity and chronicity, and immune responses
physiological function
isozyme GCYH-IB functions to allow folate biosynthesis during Zn2+ starvation
physiological function
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isozyme GCYH-IB functions to allow folate biosynthesis during Zn2+ starvation, isozyme GCYH-IB functionally replaces GCYH-IA in Bacillus subtilis under zinc-limiting conditions
physiological function
Dube3a, the fly UBE3A orthologue, positively regulates Punch/GCH1 in the fly brain. GCH1 is a UBE3A target involved in neurotransmitter regulation and has broad implications for how the function of this target may contribute to the pathogenesis of Angelman syndrome, duplication 15q autism as well as idiopathic autism linked to UBE3A regulated pathways
physiological function
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GCH1 might have broader functions beyond tetrahydrobiopterin biosynthesis. It interacts with proteins in an organ dependent manner and eukaryotic translation initiation factor 3 subunit I, EIF3I, might be a general regulator of GCH1. GCH1 is regulated by protein-protein interaction
physiological function
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GTP cyclohydrolase I interaction is required for degradation of the C-terminus of heat shock protein 70-interacting protein. GCH1 is a client protein for Hsp90. The U-box domain of CHIP is essential for ADMA-mediated GCH1 degradation in pulmonary arterial endothelial cells
physiological function
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GTP cyclohydrolase I is the rate-limiting enzyme for tetrahydrobiopterin synthesis. Cardiac myocyte-specific overexpression of human GTP cyclohydrolase I protects against acute cardiac allograft rejection
physiological function
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GTP cyclohydrolase I is the rate-limiting enzyme for tetrahydrobiopterin synthesis. Cardiac myocyte-specific overexpression of human GTP cyclohydrolase I protects against acute cardiac allograft rejection
physiological function
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GTP cyclohydrolase I, GTPCH-1, is the rate-limiting enzyme involved in de novo biosynthesis of tetrahydrobiopterin, an essential cofactor for nitric oxide synthases and aromatic amino acid hydroxylases. GTPCH-1 undergoes negative feedback regulation by its endproduct tetrahydrobiopterin via interaction with the GTP cyclohydrolase feedback regulatory protein, GFRP. GTPCH-1 levels, GTPCH-1 phosphorylation status and GFRP levels play critical roles in regulating eNOS uncoupling in response to oscillatory shear stress, overview
physiological function
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the autoinhibitory peptide provides a molecular mechanism for physiological up-regulation of GTPCH activity. GTPCH activity regulation by GTPCH feedback regulatory protein, GFRP
physiological function
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GTP cyclohydrolase I is the rate-limiting enzyme for tetrahydrobiopterin synthesis. Cardiac myocyte-specific overexpression of human GTP cyclohydrolase I protects against acute cardiac allograft rejection
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physiological function
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GCH1 might have broader functions beyond tetrahydrobiopterin biosynthesis. It interacts with proteins in an organ dependent manner and eukaryotic translation initiation factor 3 subunit I, EIF3I, might be a general regulator of GCH1. GCH1 is regulated by protein-protein interaction
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additional information
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adult cardiac myocytes despite expression of GTPCH mRNA and protein have a defective basal and cytokine-stimulated synthesis of BH4 via the de novo synthesis pathway and impaired synthesis via the salvage pathway in contrast with that typically seen in neonatal cardiac myocytes
additional information
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asymmetric dimethylarginine, ADMA, decreases GCH1 protein, but not mRNA concentrations, in pulmonary arterial endothelial cells because of the ubiquitination and proteasome-dependent degradation of GCH1. Hsp90-GCH1 interactions are reduced, whereas the association of GCH1 with Hsp70 and the C-terminus of Hsp70-interacting protein, i.e. CHIP, increases in the cells. In vivo Hsp90/GCH1 interactions are decreased, whereas GCH1-Hsp70 and GCH1-CHIP interactions and GCH1 ubiquitination are increased. L-Arginine acts antagonistic and restores the activities