GTP Cyclohydrolase 1 (GCH1)

GTPCH is encoded by the gene GCH1. The transcribed protein is the first and rate-limiting enzyme in tetrahydrobiopterin (THB) 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, 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.