GTP cyclohydrolase I

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

Gene
GTPCH is encoded by the is_associated_with::gene GCH1. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all of the variants give rise to a functional enzyme.

Clinical significance
is_associated_with::Mutations in this gene are associated with is_associated_with::malignant is_associated_with::phenylketonuria (PKU) and is_associated_with::hyperphenylalaninemia (HPA), as well as L-DOPA (Levodopa)-responsive dystonia.

Function
The transcribed is_associated_with::protein is the first and rate-limiting enzyme in is_associated_with::tetrahydrobiopterin (THB, BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-DHNP-3'-TP. THB is an essential cofactor required by the aromatic is_associated_with::amino acid is_associated_with::hydroxylase (AAAH) and is_associated_with::nitric oxide synthase (NOS) enzymes in the biosynthesis of the is_associated_with::monoamine is_associated_with::neurotransmitters is_associated_with::serotonin (5-hydroxytryptamine (5-HT)), is_associated_with::melatonin, is_associated_with::dopamine, is_associated_with::norepinephrine (noradrenaline), and is_associated_with::epinephrine (adrenaline), and is_associated_with::nitric oxide (NO), respectively.