Biomaterial Database

GTP cyclohydrolase I gene, tetrahydrobiopterin, and tyrosine hydroxylase gene: their relations to dystonia and parkinsonism. 1996

T Nagatsu, and H Ichinose

Institute of Comprehensive Medical Science, School of Medinine, Fujita Health University, Toyoake, Aichi 470-11, Japan.

Catecholamine biosynthesis is regulated by tyrosine hydroxylase (TH) requiring tetrahydrobiopterin (BH4) as the cofactor. We found four (human TH type 1-4) and two isoforms (TH type 1 and 2) in humans and monkeys, while non-primate animals have a single TH corresponding to human TH type 1. BH4 is synthesized from GTP, and GTP cyclohydrolase I (GCH) is the first and regulatory enzyme. Mutations in GCH gene were found to cause both GCH deficiency with autosomal recessive trait and hereditary progressive dystonia with marked diurnal fluctuation (HPD) (Segawa's disease)/or DOPA-responsive dystonia (DRD) with autosomal dominant trait. When GCH activity is decreased to less than 20% of the normal value, the activity of TH in the nigrostriatal dopaminergic neurons may be first decreased resulting in decreases in TH activity and dopamine level, and in the symptoms of HPD/DRD. In contrast to HPD/DRD, juvenile parkinsonism (JP) have normal GCH activity. In Parkinson's disease (PD), GCH, TH, and dopamine in the striatum may decrease in parallel, as the secondary effects caused by cell death.

UI	MeSH Term	Description	Entries
D010300	Parkinson Disease	A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)	Idiopathic Parkinson Disease,Lewy Body Parkinson Disease,Paralysis Agitans,Primary Parkinsonism,Idiopathic Parkinson's Disease,Lewy Body Parkinson's Disease,Parkinson Disease, Idiopathic,Parkinson's Disease,Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinsonism, Primary
D010302	Parkinson Disease, Secondary	Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42)	Atherosclerotic Parkinsonism,Secondary Parkinsonism,Symptomatic Parkinson Disease,Parkinson Disease, Secondary Vascular,Parkinson Disease, Symptomatic,Parkinsonism, Secondary,Parkinsonism, Symptomatic,Secondary Vascular Parkinson Disease,Parkinsonism, Atherosclerotic,Secondary Parkinson Disease,Symptomatic Parkinsonism
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004421	Dystonia	An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77)	Muscle Dystonia,Dystonia, Diurnal,Dystonia, Limb,Dystonia, Paroxysmal,Diurnal Dystonia,Dystonia, Muscle,Limb Dystonia,Paroxysmal Dystonia
D006136	GTP Cyclohydrolase	(GTP cyclohydrolase I) or GTP 7,8-8,9-dihydrolase (pyrophosphate-forming) (GTP cyclohydrolase II). An enzyme group that hydrolyzes the imidazole ring of GTP, releasing carbon-8 as formate. Two C-N bonds are hydrolyzed and the pentase unit is isomerized. This is the first step in the synthesis of folic acid from GTP. EC 3.5.4.16 (GTP cyclohydrolase I) and EC 3.5.4.25 (GTP cyclohydrolase II).	GTP 8-Formylhydrolase,GTP Dihydrolase,GTP Ring-Opening Enzyme,7,8-Dihydroneopterintriphosphate Synthetase,GTP Cyclohydrolase I,GTP Cyclohydrolase II,7,8 Dihydroneopterintriphosphate Synthetase,8-Formylhydrolase, GTP,Cyclohydrolase I, GTP,Cyclohydrolase II, GTP,Cyclohydrolase, GTP,Dihydrolase, GTP,GTP 8 Formylhydrolase,GTP Ring Opening Enzyme,Ring-Opening Enzyme, GTP,Synthetase, 7,8-Dihydroneopterintriphosphate
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000882	Haplorhini	A suborder of PRIMATES consisting of six families: CEBIDAE (some New World monkeys), ATELIDAE (some New World monkeys), CERCOPITHECIDAE (Old World monkeys), HYLOBATIDAE (gibbons and siamangs), CALLITRICHINAE (marmosets and tamarins), and HOMINIDAE (humans and great apes).	Anthropoidea,Monkeys,Anthropoids,Monkey
D001708	Biopterins	Pterin derivatives based on 2-amino-6-(1,2-dihydroxypropyl)-4(1H)-pteridinone. Biopterins are natural products that have been considered as growth factors for some insects. Biopterins are cofactors for the AROMATIC AMINO ACID hydroxylases and NITRIC OXIDE SYNTHASE. Deficiencies in BIOPTERINS metabolism (e.g., lowered TETRAHYDROBIOPTERIN) are associated with neurological deterioration (e.g., HYPERPHENYLALANINAEMIA).	2-Amino-6-((1S,2R)-1,2-dihydroxypropyl)-4(1H)-pteridinone,2-Amino-6-((1S,2S)-1,2-dihydroxypropyl)-4(1H)-pteridinone,2-Amino-6-(1,2-dihydroxypropyl)-4(8H)-pteridinone,2-amino-6-((1R,2R)-1,2-dihydroxypropyl)-4(3H)-pteridinone,4(1H)-Pteridinone, 2-amino-6-(1,2-dihydroxypropyl)-, (S-(R,S))-,6-Biopterin,Biopterin,D-threo-Biopterin,L-Biopterin,L-erythro-Biopterin,L-threo-Biopterin,2-Amino-6-(1,2-dihydroxypropyl)-4(1H)-pteridinone,Dictyopterin,Orinapterin,6 Biopterin,D threo Biopterin,L Biopterin,L erythro Biopterin,L threo Biopterin
D014446	Tyrosine 3-Monooxygenase	An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2.	Tyrosine Hydroxylase,3-Monooxygenase, Tyrosine,Hydroxylase, Tyrosine,Tyrosine 3 Monooxygenase