GTP cyclohydrolase I

GTP cyclohydrolase I (GTPCH) (EC 3.5.4.16) is a member of the GTP cyclohydrolase family of enzymes. GTPCH is part of the folate and biopterin biosynthesis pathways. It is responsible for the hydrolysis of guanosine triphosphate (GTP) to form 7,8-dihydroneopterin 3'-triphosphate (7,8-DHNP-3'-TP, 7,8-NH₂-3'-TP).

GTPCH is encoded by the gene GCH1. The transcribed protein is the first and rate-limiting enzyme in tetrahydrobiopterin (THB, BH₄) biosynthesis, catalyzing the conversion of GTP into 7,8-DHNP-3'-TP. THB is an essential cofactor required by the aromatic amino acid hydroxylase (AAAH) and nitric oxide synthase (NOS) enzymes in the biosynthesis of the monoamine neurotransmitters serotonin (5-hydroxytryptamine (5-HT)), melatonin, dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), and nitric oxide (NO), respectively. Mutations in this gene are associated with malignant phenylketonuria (PKU) and hyperphenylalaninemia (HPA), as well as L-DOPA (Levodopa)-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all of the variants give rise to a functional enzyme.^[1]

See also

• Guanosine triphosphate (GTP)
• Tetrahydrobiopterin (THB, BH₄)
• Vitamin B₉ (folic acid → folate)

References

• Voet, Judith G.; Voet, Donald (2004). Biochemistry. New York: J. Wiley & Sons. ISBN 0-471-39223-5. 
• EC 3.5.4.16 IUBMB Enzyme Nomenclature

External links

• MeSH GTP+Cyclohydrolase+I
• GeneReviews/NCBI/NIH/UW entry on GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia

NB: The numbering of the carbons of the pentose sugar is incorrect. The first carbon is the one attaching the purine and the fifth is the one attaching the phosphate. The image needs correction please.