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Gene Review

Gch1  -  GTP cyclohydrolase 1

Mus musculus

Synonyms: GTP cyclohydrolase I, GTP-CH, GTP-CH-I, GTPCH, Gch
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Disease relevance of Gch1


High impact information on Gch1

  • Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression [6].
  • 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) [6].
  • Our finding of much higher levels of BH4 and GTP cyclohydrolase, the first enzyme of de novo BH4 biosynthesis, in rat reticulocytes compared to mature erythrocytes raised the possibility that BH4 might play a role in erythrocyte maturation [7].
  • To investigate the pathophysiology, we have begun to characterize biogenic amine and BH4 metabolism in the GTP cyclohydrolase deficient hph-1 mouse [8].
  • In vitro data demonstrate that NAMDA inhibited GTP cyclohydrolase I, the rate-limiting enzyme for BH4 biosynthesis, and reduced nitrite accumulation, an oxidative metabolite of NO, without directly inhibiting NOS activity [9].

Chemical compound and disease context of Gch1


Biological context of Gch1


Anatomical context of Gch1


Associations of Gch1 with chemical compounds


Regulatory relationships of Gch1


Other interactions of Gch1


Analytical, diagnostic and therapeutic context of Gch1


  1. Stimulation of the brain NO/cyclic GMP pathway by peripheral administration of tetrahydrobiopterin in the hph-1 mouse. Canevari, L., Land, J.M., Clark, J.B., Heales, S.J. J. Neurochem. (1999) [Pubmed]
  2. Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency. Ichinose, H., Ohye, T., Matsuda, Y., Hori, T., Blau, N., Burlina, A., Rouse, B., Matalon, R., Fujita, K., Nagatsu, T. J. Biol. Chem. (1995) [Pubmed]
  3. Effects of depletion of intracellular tetrahydrobiopterin in murine erythroleukemia cells. Zhuo, S., Fan, S., Kaufman, S. Exp. Cell Res. (1996) [Pubmed]
  4. Genetically rescued tetrahydrobiopterin-depleted mice survive with hyperphenylalaninemia and region-specific monoaminergic abnormalities. Sumi-Ichinose, C., Urano, F., Shimomura, A., Sato, T., Ikemoto, K., Shiraishi, H., Senda, T., Ichinose, H., Nomura, T. J. Neurochem. (2005) [Pubmed]
  5. Molecular characterization of HPH-1: a mouse mutant deficient in GTP cyclohydrolase I activity. Gütlich, M., Ziegler, I., Witter, K., Hemmens, B., Hültner, L., McDonald, J.D., Werner, T., Rödl, W., Bacher, A. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  6. Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression. Alp, N.J., Mussa, S., Khoo, J., Cai, S., Guzik, T., Jefferson, A., Goh, N., Rockett, K.A., Channon, K.M. J. Clin. Invest. (2003) [Pubmed]
  7. Tetrahydrobiopterin, the cofactor for aromatic amino acid hydroxylases, is synthesized by and regulates proliferation of erythroid cells. Tanaka, K., Kaufman, S., Milstien, S. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  8. The hph-1 mouse: a model for dominantly inherited GTP-cyclohydrolase deficiency. Hyland, K., Gunasekara, R.S., Munk-Martin, T.L., Arnold, L.A., Engle, T. Ann. Neurol. (2003) [Pubmed]
  9. Blockade of tetrahydrobiopterin synthesis protects neurons after transient forebrain ischemia in rat: a novel role for the cofactor. Cho, S., Volpe, B.T., Bae, Y., Hwang, O., Choi, H.J., Gal, J., Park, L.C., Chu, C.K., Du, J., Joh, T.H. J. Neurosci. (1999) [Pubmed]
  10. Tetrahydrobiopterin biosynthesis in C6 glioma cells: induction of GTP cyclohydrolase I gene expression by lipopolysaccharide and cytokine treatment. D'Sa, C., Hirayama, K., West, A., Hahn, M., Zhu, M., Kapatos, G. Brain Res. Mol. Brain Res. (1996) [Pubmed]
  11. Differences in the metabolism of the aromatic amino acid hydroxylase cofactor, tetrahydrobiopterin, in mutant mice with neurological and immunological defects. Duch, D.S., Bowers, S.W., Woolf, J.H., Davisson, M.T., Maltais, L.J., Nichol, C.A. Biochem. Genet. (1986) [Pubmed]
  12. GTP cyclohydrolase I gene expression in the brains of male and female hph-1 mice. Shimoji, M., Hirayama, K., Hyland, K., Kapatos, G. J. Neurochem. (1999) [Pubmed]
  13. Peripheral administration of lipopolysaccharide enhances the expression of guanosine triphosphate cyclohydrolase I mRNA in murine locus coeruleus. Kaneko, Y.S., Mori, K., Nakashima, A., Nagatsu, I., Ota, A. Neuroscience (2003) [Pubmed]
  14. Linkage analysis of the hph-1 mutation and the GTP cyclohydrolase I structural gene. Montañez, C.S., McDonald, J.D. Mol. Genet. Metab. (1999) [Pubmed]
  15. Manipulation of the phenylalanine metabolism in human keratinocytes by retroviral mediated gene transfer. Christensen, R., Kolvraa, S., Jensen, T.G. Cells Tissues Organs (Print) (2005) [Pubmed]
  16. Biosynthesis and metabolism of pterins in peripheral blood mononuclear cells and leukemia lines of man and mouse. Schoedon, G., Troppmair, J., Fontana, A., Huber, C., Curtius, H.C., Niederwieser, A. Eur. J. Biochem. (1987) [Pubmed]
  17. In a concerted action kit ligand and interleukin 3 control the synthesis of serotonin in murine bone marrow-derived mast cells. Up-regulation of GTP cyclohydrolase I and tryptophan 5-monooxygenase activity by the kit ligand. Ziegler, I., Hültner, L., Egger, D., Kempkes, B., Mailhammer, R., Gillis, S., Rödl, W. J. Biol. Chem. (1993) [Pubmed]
  18. Characterization of transgenic mice with the expression of phenylalanine hydroxylase and GTP cyclohydrolase I in the skin. Christensen, R., Alhonen, L., Wahlfors, J., Jakobsen, M., Jensen, T.G. Exp. Dermatol. (2005) [Pubmed]
  19. Reduced tyrosine hydroxylase and GTP cyclohydrolase mRNA expression, tyrosine hydroxylase activity, and associated neurochemical alterations in Nurr1-null heterozygous mice. Eells, J.B., Misler, J.A., Nikodem, V.M. Brain Res. Bull. (2006) [Pubmed]
  20. Tetrahydrobiopterin biosynthesis, regeneration and functions. Thöny, B., Auerbach, G., Blau, N. Biochem. J. (2000) [Pubmed]
  21. Lidocaine inhibition of inducible nitric oxide synthase and cationic amino acid transporter-2 transcription in activated murine macrophages may involve voltage-sensitive Na+ channel. Huang, Y.H., Tsai, P.S., Kai, Y.F., Yang, C.H., Huang, C.J. Anesth. Analg. (2006) [Pubmed]
  22. Cardiovascular Control: Relationships between nitric oxide-mediated endothelial function, eNOS coupling and blood pressure revealed by eNOS-GTP cyclohydrolase 1 double transgenic mice. Adlam, D., Bendall, J.K., De Bono, J.P., Alp, N.J., Khoo, J., Nicoli, T., Yokoyama, M., Kawashima, S., Channon, K.M. Exp. Physiol. (2007) [Pubmed]
  23. GTP cyclohydrolase I expression, protein, and activity determine intracellular tetrahydrobiopterin levels, independent of GTP cyclohydrolase feedback regulatory protein expression. Tatham, A.L., Crabtree, M.J., Warrick, N., Cai, S., Alp, N.J., Channon, K.M. J. Biol. Chem. (2009) [Pubmed]
  24. Impact of tumour necrosis factor-alpha and interferon-gamma on tetrahydrobiopterin synthesis in murine fibroblasts and macrophages. Werner, E.R., Werner-Felmayer, G., Fuchs, D., Hausen, A., Reibnegger, G., Yim, J.J., Wachter, H. Biochem. J. (1991) [Pubmed]
  25. Regulation of GTP cyclohydrolase I expression by orphan receptor Nurr1 in cell culture and in vivo. Gil, M., McKinney, C., Lee, M.K., Eells, J.B., Phyillaier, M.A., Nikodem, V.M. J. Neurochem. (2007) [Pubmed]
  26. Molecular cloning of a cDNA coding for GTP cyclohydrolase I from Dictyostelium discoideum. Witter, K., Cahill, D.J., Werner, T., Ziegler, I., Rödl, W., Bacher, A., Gütlich, M. Biochem. J. (1996) [Pubmed]
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