Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

3.5.4.16

Official Name

GTP cyclohydrolase I

Name from literature

GTP cyclohydrolase 1

Pathway from literature

BH4 synthesis/the biosynthesis of tetrahydrobiopterin (BH(4)),a natural cofactor for tyrosine and tryptophan hydroxylases

Pathway from KEGG

Metabolism of Cofactors and Vitamins; Folate biosynthesis; map00790

Organisms

Rat (10116)

Genome localization

15p14[29244 ],

Comments

The reaction involves hydrolysis of two C-N bonds and isomerization of the pentose unit; the recyclization may be non-enzymic. This enzyme is involved in the de novo synthesis of tetrahydrobiopterin from GTP, with the other enzymes involved being EC 1.1.1.153 (sepiapterin reductase) and EC 4.2.3.12 (6-pyruvoyltetrahydropterin synthase) [3].

Rate-limiting Description

"These findings reveal the significance of estrogen in modulating regulation of rate limiting enzyme in the (6R)-5,6,7,8-tetrahydrobiopterin biosynthesis, which may have implications for sex-related differences in vulnerability in related disorders." (16650618)

"The central hypothesis of this study is that coexpression of four dopamine biosynthetic and transporter genes in striatal neurons can support the efficient production and regulated, vesicular release of dopamine: tyrosine hydroxylase (TH) converts tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), GTP cyclohydrolase I (GTP CH I) is the rate-limiting enzyme in the biosynthesis of the cofactor for TH, aromatic amino acid decarboxylase (AADC) converts L-DOPA to dopamine, and a vesicular monoamine transporter (VMAT-2) transports dopamine into synaptic vesicles, thereby supporting regulated, vesicular release of dopamine and relieving feedback inhibition of TH by dopamine." (15684695)

"GTP cyclohydrolase I (GCH) is the first and rate-limiting enzyme in the biosynthesis of 5,6,7,8-tertahydrobiopterin (BH4), the required cofactor for tyrosine hydroxylase." (16190874)

Regulatory Information

Upstream transcription factor

24790;367846

Regulatory type

Detail

feedback;

"conformational analysis of GTP cyclohydrolase I binding GFRP, its feedback regulatory protein" (15448133)

transcriptional factor;Sp1(24790),Sp3(367846)

"Sp1 and Sp3 are found associated with native proximal promoter of cyclic AMP (cAMP)-dependent GTP cyclohydrolase I in PC12 cells but are not recruited to the promoter during cAMP-dependent transcription." (18004997)

Gene ontology

Gene ontology

GO:0008270 (F) zinc ion binding [P22288 ];
GO:0006729 (P) tetrahydrobiopterin biosynthetic process [P22288 ];
GO:0048265 (P) response to pain [P22288 ];
GO:0003934 (F) GTP cyclohydrolase I activity [P22288 ];
GO:0005737 (C) cytoplasm [P22288 ];

Links

SwissProt

P22288

Entrez Gene

29244



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  Last Modified: 2009-03-24  
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