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

Basic Information

Enzyme Number

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


Human (9606)

Genome localization

14q22.1-q22.2[2643 ],


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 (sepiapterin reductase) and EC (6-pyruvoyltetrahydropterin synthase) [3].

Rate-limiting Description

"BACKGROUND: GTP-cyclohydrolase I, encoded by the GCH1 gene, is the rate-limiting enzyme in the biosynthesis of BH4, an eNOS cofactor important for maintaining enzymatic coupling." (18598896)

Regulatory Information

Regulatory type


transcriptional factor;"basic region leucine zipper transcription factors(10538,116071)"

"GTP cyclohydrolase I gene transcription is regulated by basic region leucine zipper transcription factors" (16149046)



transcriptional level;TNF-alpha(7124)

"Incubating HUVECs with tumor necrosis factor (TNF-alpha) was observed to increase GTPCH mRNA while decreasing eNOS mRNA." (12588756)

Gene ontology

Gene ontology

GO:0034612 (P) response to tumor necrosis factor [P30793 ];
GO:0008270 (F) zinc ion binding [P30793 ];
GO:0043234 (C) protein complex [P30793 ];
GO:0005525 (F) GTP binding [P30793 ];
GO:0051260 (P) protein homooligomerization [P30793 ];
GO:0032496 (P) response to lipopolysaccharide [P30793 ];
GO:0006559 (P) L-phenylalanine catabolic process [P30793 ];
GO:0005829 (C) cytosol [P30793 ];
GO:0050884 (P) neuromuscular process controlling posture [P30793 ];
GO:0006729 (P) tetrahydrobiopterin biosynthetic process [P30793 ];
GO:0006809 (P) nitric oxide biosynthetic process [P30793 ];
GO:0008217 (P) regulation of blood pressure [P30793 ];
GO:0042803 (F) protein homodimerization activity [P30793 ];
GO:0034341 (P) response to interferon-gamma [P30793 ];
GO:0051000 (P) positive regulation of nitric-oxide synthas... [P30793 ];
GO:0006184 (P) GTP catabolic process [P30793 ];
GO:0031410 (C) cytoplasmic vesicle [P30793 ];
GO:0042416 (P) dopamine biosynthetic process [P30793 ];
GO:0048265 (P) response to pain [P30793 ];
GO:0005634 (C) nucleus [P30793 ];
GO:0003934 (F) GTP cyclohydrolase I activity [P30793 ];

Disease relevance


Defects in GCH1 are the cause of atypical severe phenylketonuria (PKU) [MIM:233910]. It is a disease characterized by hyperphenylalaninemia (HPA), progressive neurologic illness with severe muscular hypotonia [P30793 ];

Defects in GCH1 are the cause of autosomal dominant dopa-responsive dystonia (DRD) [MIM:128230];
also known as dystonia-5 (DYT5), progressive dystonia with diurnal fluctuation, autosomal dominant Segawa syndrome or dystonia-parkinsonism with diurnal fluctuation. DRD is characterized by postural and motor disturbances showing marked diurnal fluctuation [P30793 ];




Entrez Gene




  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min