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

Mouse (10090)

Genome localization

14 C2-3|14 19.5 cM[14528 ],

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

"We previously described that hydrogen peroxide (H(2)O(2)) increases BH4 levels through the induction of GTP-cyclohydrolase I (GTPCH), which is the rate-limiting enzyme for the synthesis of BH4, in vascular endothelial cells." (18054268)

"It has been reported that activation of the immune system stimulates an increase in endogenous BH4 rate-limiting enzyme GTP cyclohydrolase I (GTPCH I) activity, resulting in an increase in intracellular BH4 levels and BH4-dependent NO synthesis in various cells." (17978343)

"Guanosine 5'-triphosphate-cyclohydrolase I (GTPCH) is the first rate-limiting enzyme for de novo BH(4) synthesis." (17973864)

"Here, we demonstrate that diabetes reduced BH4 by increasing 26S proteasome-dependent degradation of guanosine 5'-triphosphate cyclohydrolase I (GTPCH), a rate-limiting enzyme in the synthesis of BH4, in parallel with increased formation of both superoxide and peroxynitrite (ONOO-)." (17679617)

"GTP cyclohydrolase I (GTPCH I) is the rate-limiting enzyme for de novo BH4 synthesis." (18268143)

"GTP-cyclohydrolase 1 (GTP-CH1) catalyses the first and rate-limiting step for the de novo production of tetrahydrobiopterin (BH(4)), an essential cofactor for nitric oxide synthase (NOS)." (18372436)

"METHODS AND RESULTS: We crossed mice overexpressing eNOS in the endothelium (eNOS-Tg) with mice overexpressing GTP-cyclohydrolase I (GCH), the rate-limiting enzyme in BH4 synthesis, to generate ApoE-KO/eNOS-Tg/GCH-Tg mice." (17463333)

"GTP cyclohydrolase 1 (GTPCH1) is the rate-limiting enzyme in de novo synthesis of tetrahydrobiopterin (BH4), an essential cofactor for endothelial NO synthase (eNOS) dictating, at least partly, the balance of NO and superoxide produced by this enzyme." (18645049)

Regulatory Information

Regulatory type

Detail

phosphorylation;

Q05915

phosphorylation;

"endothelium-specific GTPCH I overexpression abrogates O2(-) production and preserves eNOS phosphorylation, with preserved structural and functional integrity of resistance mesenteric arteries and lowered blood pressure in low-renin hypertension" (18268143)

Gene ontology

Gene ontology

GO:0008270 (F) zinc ion binding [Q05915 ];
GO:0014916 (P) regulation of lung blood pressure [Q05915 ];
GO:0006729 (P) tetrahydrobiopterin biosynthetic process [Q05915 ];
GO:0048265 (P) response to pain [Q05915 ];
GO:0003934 (F) GTP cyclohydrolase I activity [Q05915 ];
GO:0005737 (C) cytoplasm [Q05915 ];

Links

SwissProt

Q05915

Entrez Gene

14528



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  Last Modified: 2009-03-24  
  Design by Zhao Min