関: GTP cyclohydrolase、GTPCHI

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the 9th letter of the Roman alphabet (同)i
the 7th letter of the Roman alphabet (同)g

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/25 17:12:03」(JST)

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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 triphosphate (7,8-DHNP-3'-TP, 7,8-NH₂-3'-TP).

Gene

GTPCH is encoded by the 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.^[1]

Clinical significance

Mutations in this gene are associated with malignant phenylketonuria (PKU) and hyperphenylalaninemia (HPA), as well as GTP cyclohydrolase I deficiency.^[1] Deficiency of GTP cyclohydrolase I can occur in a recessive and in a dominant form and lead to a lacl of certain neurotrasmitters (dopamine, norepinephrine, epinephrine and serotonin). The dominant form, with mutation in only one of the two alleles for GTP cyclohydrolase I, causes dopamine-responsive dystonia, characterized by childhood-onset dystonia. Patients with the recessive form have mutations in both alleles for GTP cyclohydrolase I. Patients present with developmental delays and neurological dysfunction with trunk hypotonia, hypertonia of the extremities, abnormal movements, tremors, convulsions, and sometimes autonomic dysfunction. ^[2] Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD). ^[3]

Function

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.

References

^ ^a ^b "Entrez Gene: GCH1 GTP Cyclohydrolase 1 (DOPA-Responsive Dystonia).".
^ Longo N (June 2009). "Disorders of biopterin metabolism". J Inherit Metab Dis 32 (2): 333–342. doi:10.1007/s10545-009-1067-2. PMID 19234759.
^ "Patient registry".

External links

GTP Cyclohydrolase I at the US National Library of Medicine Medical Subject Headings (MeSH)
GeneReviews/NCBI/NIH/UW entry on GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia

Molecular and Cellular Biology portal

UpToDate Contents

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1. ジストニアの分類および評価 classification and evaluation of dystonia
2. 小児における運動過多な運動障害 hyperkinetic movement disorders in children

English Journal

Selective depletion of vascular EC-SOD augments chronic hypoxic pulmonary hypertension.

Nozik-Grayck E1, Woods C2, Taylor JM3, Benninger RK4, Johnson RD2, Villegas LR2, Stenmark KR2, Harrison DG5, Majka SM5, Irwin DC6, Farrow KN7.
American journal of physiology. Lung cellular and molecular physiology.Am J Physiol Lung Cell Mol Physiol.2014 Oct 17. pii: ajplung.00096.2014. [Epub ahead of print]
Excess superoxide has been implicated in pulmonary hypertension (PH). We previously found that lung overexpression of the antioxidant extracellular superoxide dismutase (EC-SOD) attenuates PH and vascular remodeling. Though comprising only a small fraction of total SOD activity in most tissues, EC-S
PMID 25326578

Changes in gene expression and methylation in the blood of patients with first-episode psychosis.

Ota VK1, Noto C2, Gadelha A3, Santoro ML4, Spindola LM5, Gouvea ES6, Stilhano RS7, Ortiz BB8, Silva PN9, Sato JR10, Han SW11, Cordeiro Q12, Bressan RA13, Belangero SI14.
Schizophrenia research.Schizophr Res.2014 Sep 27. pii: S0920-9964(14)00474-5. doi: 10.1016/j.schres.2014.09.008. [Epub ahead of print]
Schizophrenia is a severe mental health disorder with high heritability. The investigation of individuals during their first-episode psychosis (FEP), before the progression of psychotic disorders and especially before treatment with antipsychotic medications, is particularly helpful for understandin
PMID 25270546

Parkinson's disease in GTP cyclohydrolase 1 mutation carriers.

Mencacci NE1, Isaias IU2, Reich MM3, Ganos C4, Plagnol V5, Polke JM6, Bras J7, Hersheson J7, Stamelou M8, Pittman AM9, Noyce AJ9, Mok KY7, Opladen T10, Kunstmann E11, Hodecker S12, Münchau A13, Volkmann J14, Samnick S15, Sidle K7, Nanji T6, Sweeney MG6, Houlden H7, Batla A16, Zecchinelli AL14, Pezzoli G14, Marotta G17, Lees A18, Alegria P19, Krack P20, Cormier-Dequaire F21, Lesage S22, Brice A23, Heutink P24, Gasser T24, Lubbe SJ25, Morris HR25, Taba P26, Koks S27, Majounie E28, Raphael Gibbs J28, Singleton A28, Hardy J9, Klebe S3, Bhatia KP29, Wood NW30; International Parkinson’s Disease Genomics Consortium and UCL-exomes consortium.
Brain : a journal of neurology.Brain.2014 Sep;137(Pt 9):2480-92. doi: 10.1093/brain/awu179. Epub 2014 Jul 2.
GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease
PMID 24993959

Japanese Journal

NO代謝(テトラヒドロビオプテリンおよびその合成律速酵素GTP cyclohydrolase I)の糖代謝調節機構への関与 (特集血管内皮と糖尿病とその合併症)

藤田義人
内分泌・糖尿病・代謝内科 39(6), 442-448, 2014-12
NAID 40020314340

ビオプテリンの生理機能と病態代謝

一瀬宏
ビタミン 88(3), 131-138, 2014-03-25
… GTP cyclohydrolase I is an enzyme for BH4-biosynthesis and the genetic defect in an allele of GTP cyclohydrolase I gene can cause hereditary dystonia, termed as DYT5, due to partial BH4 deficiency. …
NAID 110009807287

脳性麻痺と診断されていた瀬川病の女性例

村上てるみ,西村敏,舟塚真 [他],新宅治夫,一瀬宏,大澤眞木子
東京女子医科大学雑誌 83(E3), E663-E665, 2013-07-31
… 瀬川病は14q22.1-q22.2に存在するGTPシクロヒドロラーゼI(GCH1)遺伝子異常に起因する常染色体優性遺伝性ジストニーである。 … 髄液中のネオプテリン、バイオプテリンの低値と血球中のGTPシクロヒドラーゼI(GCH1)酵素活性低値、さらにGCH1遺伝子異常を認め瀬川病と確定診断した。 …
NAID 110009604924

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リンク元	「GTPシクロヒドロラーゼI」「GTP cyclohydrolase」「GCHI」「GTPCHI」
拡張検索	「GTP cyclohydrolase I gene mutation」「GTP cyclohydrolase I deficiency」
関連記事	「I」「GTP」「GTP cyclohydrolase」「G」「Id」

「GTPシクロヒドロラーゼI」

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PMC	articles
PubMed	articles
NCBI	proteins

	The chemical reaction performed by GTPCH. The important carbons relative to the transformation are numbered for reference.
Identifiers
EC number	3.5.4.16
CAS number	37289-19-3
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
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PMC	articles
PubMed	articles
NCBI	proteins

GTP cyclohydrolase 1
	PDB rendering based on 1fb1.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1FB1
Identifiers
Symbols	GCH1 ; DYT14; DYT5; DYT5a; GCH; GTP-CH-1; GTPCH1; HPABH4B
External IDs	OMIM: 600225 MGI: 95675 HomoloGene: 132 GeneCards: GCH1 Gene
EC number	3.5.4.16
Gene ontology
Molecular function	• GTP cyclohydrolase I activity; • calcium ion binding; • protein binding; • GTP binding; • zinc ion binding; • GTP-dependent protein binding; • protein homodimerization activity; • coenzyme binding;
Cellular component	• nucleus; • nucleoplasm; • cytoplasm; • cytosol; • cytoplasmic vesicle; • nuclear membrane; • protein complex;
Biological process	• tetrahydrobiopterin biosynthetic process; • nitric oxide biosynthetic process; • regulation of blood pressure; • regulation of lung blood pressure; • response to lipopolysaccharide; • response to interferon-gamma; • response to tumor necrosis factor; • 7,8-dihydroneopterin 3'-triphosphate biosynthetic process; • vasodilation; • dopamine biosynthetic process; • pteridine-containing compound biosynthetic process; • small molecule metabolic process; • negative regulation of blood pressure; • nitric oxide metabolic process; • tetrahydrofolate biosynthetic process; • response to pain; • neuromuscular process controlling posture; • regulation of nitric-oxide synthase activity; • positive regulation of nitric-oxide synthase activity; • protein homooligomerization; • protein heterooligomerization;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;