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GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
dihydroneopterin triphosphate + formate
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
GTP + H2O
formate + 7,8-dihydroneopterin 3'-triphosphate
-
-
-
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
additional information
?
-
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
rate-limiting step in the biosynthesis of tetrahydrobiopterin, a key factor necessary for nitric oxide synthase, and for the hydrolxylases that are involved in the production of catecholamines and serotonin
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
estrogens play a regulatory role on the enzyme expression, the enzyme is involved in estrogen receptor interaction with cyclic AMP, role of receptor subtypes, overview
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
the enzyme controls the biosynthesis pathway of tetrahydrobiopterin, which is a necessary cofactor for inducible nitric oxide synthase
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
the enzyme is feedback regulated by the GTPCH feedback regulatory protein GFRP, overview
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
-
first step in pathway of pterins
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
-
-
-
-
?
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
-
first step of the biosynthesis of (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, i.e. BH4
-
-
?
additional information
?
-
-
enzyme deficiency causes hyperphenylalaninemia with severe neurological disorders, the 3,4-dihydroxyphenylalanine, i.e. DOPA, responsive form of dystonia, and endothelial dysfunction, all by (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin depletion, the GTP cyclohydrolase I feedback regulatory protein GFRP binds to the enzyme and mediates the regulation of the enzyme by L-phenylalanine and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
-
?
additional information
?
-
-
tetrahydrobiopterin, the cofactor required for hydroxylation of aromatic amino acids, regulates its own synthesis through feedback inhibition of the enzyme mediated by the regulatory subunit called GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
-
-
?
additional information
?
-
-
enzyme is complexed with the GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP, in a ratio of 1:2, complex formation is induced by phenylalanine and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
-
?
additional information
?
-
-
enzyme is complexed with the GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP, in a ratio of 1:2, complex formation is induced by phenylalanine and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, i.e. BH4
-
-
?
additional information
?
-
-
GCH-1 interacts with many signal transduction proteins such as receptors (NKG2-A/B-actvating NK receptor and latrophilin-2), kinase (Death-associated protein kinase 3), adaptors (Rho-GTPase-activating protein 7 and Rho-guanine nucleotide exchange factor 3) and transcriptional factors (ATF-6 alpha and interferon regulatory factor 1)
-
-
?
additional information
?
-
-
GCH1 interacts with GCH1 interacts with GTP cyclohydrolase I feedback regulatory protein, GFRP, and very long-chain specific acyl-CoA dehydrogenase in the liver, tubulin beta-2A chain in the liver and brain, DnaJ homolog subfamily A member 1 and fatty aldehyde dehydrogenase in the liver, heart and kidney and eukaryotic translation initiation factor 3 subunit I in all organs tested, overview. GCH1 associates with mitochondrial proteins and interacts with VLCAD, a mitochondrial protein
-
-
?
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GTP + H2O
dihydroneopterin triphosphate + formate
-
-
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
GTP + H2O
formate + D-erythro-dihydroneopterin triphosphate
-
first step of the biosynthesis of (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, i.e. BH4
-
-
?
additional information
?
-
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
rate-limiting step in the biosynthesis of tetrahydrobiopterin, a key factor necessary for nitric oxide synthase, and for the hydrolxylases that are involved in the production of catecholamines and serotonin
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
estrogens play a regulatory role on the enzyme expression, the enzyme is involved in estrogen receptor interaction with cyclic AMP, role of receptor subtypes, overview
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
the enzyme controls the biosynthesis pathway of tetrahydrobiopterin, which is a necessary cofactor for inducible nitric oxide synthase
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
the enzyme is feedback regulated by the GTPCH feedback regulatory protein GFRP, overview
-
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
-
first step in pathway of pterins
-
?
GTP + H2O
formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)dihydropteridine triphosphate
-
first step in pathway of pterins
-
?
additional information
?
-
-
enzyme deficiency causes hyperphenylalaninemia with severe neurological disorders, the 3,4-dihydroxyphenylalanine, i.e. DOPA, responsive form of dystonia, and endothelial dysfunction, all by (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin depletion, the GTP cyclohydrolase I feedback regulatory protein GFRP binds to the enzyme and mediates the regulation of the enzyme by L-phenylalanine and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
-
?
additional information
?
-
-
tetrahydrobiopterin, the cofactor required for hydroxylation of aromatic amino acids, regulates its own synthesis through feedback inhibition of the enzyme mediated by the regulatory subunit called GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
-
-
?
additional information
?
-
-
GCH1 interacts with GCH1 interacts with GTP cyclohydrolase I feedback regulatory protein, GFRP, and very long-chain specific acyl-CoA dehydrogenase in the liver, tubulin beta-2A chain in the liver and brain, DnaJ homolog subfamily A member 1 and fatty aldehyde dehydrogenase in the liver, heart and kidney and eukaryotic translation initiation factor 3 subunit I in all organs tested, overview. GCH1 associates with mitochondrial proteins and interacts with VLCAD, a mitochondrial protein
-
-
?
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(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
2,4-Diamino-6-hydroxypyrimidine
dihydrobiopterin
-
induction of feedback inhibition, binding site structure
GTP
-
substrate inhibition above 0.2 mM
GTP cyclohydrolase I feedback regulatory protein GFRP
-
natural inhibitor, inhibition mechanism, in vitro inhibition together with 2,4-diamino-6-hydroxypyrimidine, the inhibition is fully reversible by L-phenylalanine, regulatory function in physiological feedback inhibition, overview
-
GTPCH feedback regulatory protein
-
GFRP, the allosteric regulatory protein GFRP triggers a noncompetitive attenuation of GTPCH activity, an allosteric effector is unnecessary for GFRP to influence GTPCH activity. GFRP-mediated allosteric regulation by small molecule effectors is indistinguishable for truncated mutant DELTA45-GTPCH and wild-type GTPCH
-
L-erythro-5,6,7,8-tetrahydrobiopterin
streptozotocin
-
the expression of GCH-I is decreased by streptozotocin treatment (60 mg/kg iv, 7 weeks)
additional information
-
the N-terminal peptide of mammalian GTP cyclohydrolase I is an autoinhibitory control element and contributes to binding the allosteric regulatory protein GFRP. The autoinhibitory peptide provides a molecular mechanism for physiological up-regulation of GTPCH activity
-
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
i.e. BH4, feedback inhibition mediated by GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP, in complex with the enzyme, binding site structure
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
i.e. BH4, feedback inhibition mediated by GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP, inhibition is enhaced by dGTP
2,4-Diamino-6-hydroxypyrimidine
-
direct inhibitition at higher concentrations
2,4-Diamino-6-hydroxypyrimidine
-
DAHP, the inhibition mechanism involves the GTP cyclohydrolase I feedback regulatory protein GFRP, overview, the inhibition is fully reversible by L-phenylalanine
L-erythro-5,6,7,8-tetrahydrobiopterin
-
indirect inhibition of 2,4-diamino-6-hydroxypyrimidine at lower concentrations with the help of feedback regulatory protein
L-erythro-5,6,7,8-tetrahydrobiopterin
-
L-phenylalanine reverses inhibition
L-erythro-5,6,7,8-tetrahydrobiopterin
-
with help of feedback regulatory protein
tetrahydrobiopterin
-
induction of feedback inhibition of the enzyme via mediation of GFRP which forms a complex with the enzyme, binding site structure
tetrahydrobiopterin
-
the cofactor required for hydroxylation of aromatic amino acids regulates its own synthesis through feedback inhibition of the enzyme mediated by the regulatory subunit called GTP cyclohydrolase I feedback regulatory protein, i.e. GFRP
tetrahydrobiopterin
-
BH4, can limit its own synthesis by triggering decameric GTPCH to assemble in an inhibitory complex with two GTPCH feedback regulatory protein, GFRP, pentamers
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Sawada, M.; Horikoshi, T.; Masada, M.; Akino, M.; Sugimoto, T.M.; Matsuura, S.; Nagatsu, T.
A sensitive assay of GTP cyclohydrolase I activity in rat and human tissues using radioimmunoassay of neopterin
Anal. Biochem.
154
361-366
1986
Homo sapiens, Rattus norvegicus
brenda
Blau, N.; Niederwieser, A.
GTP-cyclohydrolases: a review
J. Clin. Chem. Clin. Biochem.
23
169-176
1985
Geobacillus stearothermophilus, Comamonas sp., Escherichia coli, Lactiplantibacillus plantarum, Mammalia, Rattus norvegicus, Serratia indica
brenda
Blau, N.; Niederwieser, A.
GTP-cyclohydrolases: mini-review
Biochem. Clin. Aspects Pteridines
3
77-92
1984
Geobacillus stearothermophilus, Gallus gallus, Comamonas sp., Drosophila melanogaster, Escherichia coli, Lactiplantibacillus plantarum, Rattus norvegicus, Serratia indica
-
brenda
Hatakeyama, K.; Harada, T.; Kagamiyama, H.
IMP dehydrogenase inhibitors reduce intracellular tetrahydrobiopterin levels through reduction of intracellular GTP levels
J. Biol. Chem.
267
20734-20739
1992
Homo sapiens, Rattus norvegicus
brenda
Xie, L.; Smith, J.A.; Gross, S.S.
GTP cyclohydrolase I inhibition by the prototypic inhibitor 2,4-diamino-6-hydroxypyrimidine
J. Biol. Chem.
273
21091-21098
1998
Rattus norvegicus
brenda
Yoneyama, T.; Brewers, J.M.; Hatakeyama, K.
GTP cyclohydrolase I feedback regulatory protein is a pentamer of identical subunits
J. Biol. Chem.
272
9690-9696
1997
Rattus norvegicus
brenda
Milstien, S.; Jaffe, H.; Kowlessu, D.; Bonner, T.I.
Purification and cloning of the GTP cyclohydrolase I feedback regulatory protein, GFRP
J. Biol. Chem.
271
19743-19751
1996
Rattus norvegicus
brenda
Hattori, Y.; Gross, S.S.
GTP cyclohydrolase I mRNA is induced by LPS in vascular smooth muscle: Characterization, sequence and relationship to nitric oxide synthase
Biochem. Biophys. Res. Commun.
195
435-441
1993
Rattus norvegicus
brenda
Maita, N.; Hatakeyama, K.; Okada, K.; Hakoshima, T.
Structural basis of biopterin-induced inhibition of GTP cyclohydrolase I by GFRP, its feedback regulatory proteins
J. Biol. Chem.
279
51534-51540
2004
Rattus norvegicus
brenda
Bader, G.; Schiffmann, S.; Herrmann, A.; Fischer, M.; Gutlich, M.; Auerbach, G.; Ploom, T.; Bacher, A.; Huber, R.; Lemm, T.
Crystal structure of rat GTP cyclohydrolase I feedback regulatory protein, GFRP
J. Mol. Biol.
312
1051-1057
2001
Rattus norvegicus
brenda
Maita, N.; Okada, K.; Hatakeyama, K.; Hakoshima, T.
Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP
Proc. Natl. Acad. Sci. USA
99
1212-1217
2002
Rattus norvegicus
brenda
Yoneyama, T.; Hatakeyama, K.
Ligand binding to the inhibitory and stimulatory GTP cyclohydrolase I/GTP cyclohydrolase I feedback regulatory protein complexes
Protein Sci.
10
871-878
2001
Rattus norvegicus
brenda
Hung, Y.C.; Tsai, P.S.; Huang, C.J.; Yang, S.; Skimming, J.W.; Hsieh, M.C.
Change in expression of the guanosine triphosphate cyclohydrolase I in LPS-stimulated rats is tissue specific
Acta Anaesthesiol. Taiwan.
42
23-31
2004
Rattus norvegicus
brenda
Kolinsky, M.A.; Gross, S.S.
The mechanism of potent GTP cyclohydrolase I inhibition by 2,4-diamino-6-hydroxypyrimidine: requirement of the GTP cyclohydrolase I feedback regulatory protein
J. Biol. Chem.
279
40677-40682
2004
Rattus norvegicus
brenda
Serova, L.I.; Filipenko, M.; Schilt, N.; Veerasirikul, M.; Sabban, E.L.
Estrogen-triggered activation of GTP cyclohydrolase 1 gene expression: Role of estrogen receptor subtypes and interaction with cyclic AMP
Neuroscience
140
1253-1263
2006
Rattus norvegicus
brenda
Seujange, Y.; Eiam-Ong, S.; Tirawatnapong, T.; Eiam-Ong, S.
Role of angiotensin II on dihydrofolate reductase, GTP-cyclohydrolase 1 and nitric oxide synthase expressions in renal ischemia-reperfusion
Am. J. Nephrol.
28
692-700
2008
Rattus norvegicus (P22288), Rattus norvegicus
brenda
Wenzel, P.; Schulz, E.; Oelze, M.; Mueller, J.; Schuhmacher, S.; Alhamdani, M.S.; Debrezion, J.; Hortmann, M.; Reifenberg, K.; Fleming, I.; Muenzel, T.; Daiber, A.
AT1-receptor blockade by telmisartan upregulates GTP-cyclohydrolase I and protects eNOS in diabetic rats
Free Radic. Biol. Med.
45
619-626
2008
Rattus norvegicus
brenda
Du, J.; Wei, N.; Xu, H.; Ge, Y.; Vasquez-Vivar, J.; Guan, T.; Oldham, K.T.; Pritchard, K.A.; Shi, Y.
Identification and functional characterization of phosphorylation sites on GTP cyclohydrolase I
Arterioscler. Thromb. Vasc. Biol.
29
2161-2168
2009
Rattus norvegicus
brenda
Du, J.; Xu, H.; Wei, N.; Wakim, B.; Halligan, B.; Pritchard, K.A.; Shi, Y.
Identification of proteins interacting with GTP cyclohydrolase I
Biochem. Biophys. Res. Commun.
385
143-147
2009
Rattus norvegicus
brenda
Higgins, C.E.; Gross, S.S.
The N-terminal peptide of mammalian GTP cyclohydrolase I is an autoinhibitory control element and contributes to binding the allosteric regulatory protein GFRP
J. Biol. Chem.
286
11919-11928
2011
Rattus norvegicus
brenda
Du, J.; Teng, R.J.; Lawrence, M.; Guan, T.; Xu, H.; Ge, Y.; Shi, Y.
The protein partners of GTP cyclohydrolase I in rat organs
PLoS ONE
7
e33991
2012
Rattus norvegicus, Rattus norvegicus Sprague Dawley
brenda