PMID: 9182249Feb 1, 1996Paper

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

Neurochemical Research
T Nagatsu, H Ichinose

Abstract

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.

References

Aug 31, 1992·Biochemical and Biophysical Research Communications·A TogariT Nagatsu
Oct 1, 1991·Neuroscience Research·T Nagatsu
Jan 1, 1985·Annual Review of Biochemistry·C A NicholD S Duch
Oct 10, 1988·FEBS Letters·K KobayashiT Nagatsu
Mar 1, 1995·Neurodegeneration : a Journal for Neurodegenerative Disorders, Neuroprotection, and Neuroregeneration·T OhyeT Nagatsu
May 5, 1995·Neuroscience Letters·H IchinoseT Nagatsu
Aug 31, 1993·Biochemical and Biophysical Research Communications·H IchinoseT Nagatsu
Jan 1, 1994·Journal of Neural Transmission. Parkinson's Disease and Dementia Section·H IchinoseT Nagatsu
Apr 1, 1994·Annals of Neurology·A H RajputO Hornykiewicz
Dec 1, 1993·Nature Genetics·T G NygaardD E Weeks
Jan 1, 1995·Journal of Neural Transmission. General Section·T NomuraT Nagatsu
Dec 1, 1963·Proceedings of the National Academy of Sciences of the United States of America·S KAUFMAN

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Citations

Sep 1, 1997·Nature Medicine·O Isacson, X O Breakefield
Nov 1, 2007·International Journal of Clinical Practice·N Gordon
Dec 16, 2017·Genes, Brain, and Behavior·Y Jung, D Goldman
Sep 8, 2009·Movement Disorders : Official Journal of the Movement Disorder Society·Christine KleinAnthony E Lang
Jun 11, 2020·Current Opinion in Neurology·Dora Steel, Manju A Kurian
May 26, 2017·Frontiers in Molecular Neuroscience·Andrea BednářováNatraj Krishnan
Sep 4, 2003·Journal of Neuro-oncology·Maciej S LesniakHenry Brem
Jul 14, 2020·Current Opinion in Neurology·Dora Steel, Manju A Kurian

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