GCH1 Antibody – Rabbit Polyclonal

This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme. [provided by RefSeq, Jul 2008]

GCH1: Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown. Defects in GCH1 are the cause of GTP cyclohydrolase 1 deficiency (GCH1D); also known as atypical severe phenylketonuria due to GTP cyclohydrolase I deficiency;. GCH1D is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. It is also responsible for defective neurotransmission due to depletion of the neurotransmitters dopamine and serotonin. The principal symptoms include: psychomotor retardation, tonicity disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing. Some patients may present a phenotype of intermediate severity between severe hyperphenylalaninemia and mild dystonia type 5 (dystonia- parkinsonism with diurnal fluctuation). In this intermediate phenotype, there is marked motor delay, but no mental retardation and only minimal, if any, hyperphenylalaninemia. Defects in GCH1 are the cause of dystonia type 5 (DYT5); also known as progressive dystonia with diurnal fluctuation, autosomal dominant Segawa syndrome or dystonia- parkinsonism with diurnal fluctuation. DYT5 is a DOPA-responsive dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT5 typically presents in childhood with walking problems due to dystonia of the lower limbs and worsening of the dystonia towards the evening. It is characterized by postural and motor disturbances showing marked diurnal fluctuation. Torsion of the trunk is unusual. Symptoms are alleviated after sleep and aggravated by fatigue and excercise. There is a favorable response to L-DOPA without side effects. Belongs to the GTP cyclohydrolase I family. 4 isoforms of the human protein are produced by alternative splicing.

Protein type: Hydrolase; Cofactor and Vitamin Metabolism - folate biosynthesis; EC 3.5.4.16

Chromosomal Location of Human Ortholog: 14q22.1-q22.2

Cellular Component: nucleoplasm; nuclear membrane; protein complex; cytoplasm; cytoplasmic vesicle; cytosol; nucleus

Molecular Function: GTP cyclohydrolase I activity; protein binding; protein homodimerization activity; GTP binding; zinc ion binding; GTP-dependent protein binding; calcium ion binding; coenzyme binding

Biological Process: tetrahydrobiopterin biosynthetic process; regulation of lung blood pressure; protein heterooligomerization; metabolic process; positive regulation of nitric-oxide synthase activity; response to lipopolysaccharide; response to pain; dopamine biosynthetic process; pteridine and derivative biosynthetic process; nitric oxide metabolic process; vasodilation; neuromuscular process controlling posture; tetrahydrofolate biosynthetic process; regulation of blood pressure; negative regulation of blood pressure; regulation of nitric-oxide synthase activity; nitric oxide biosynthetic process; protein homooligomerization

Disease: Hyperphenylalaninemia, Bh4-deficient, B; Dystonia, Dopa-responsive