Role of N-terminus of tyrosine hydroxylase in the biosynthesis of catecholamines

  title={Role of N-terminus of tyrosine hydroxylase in the biosynthesis of catecholamines},
  author={Akira Nakashima and Nobuhiro Hayashi and Yoko S. Kaneko and Keiji Mori and Esther L. Sabban and Toshiharu Nagatsu and Akira Ota},
  journal={Journal of Neural Transmission},
Tyrosine hydroxylase (TH) catalyzes the conversion of l-tyrosine to l-dopa, which is the initial and rate-limiting step in the biosynthesis of catecholamines [CA; dopamine (DA), noradrenaline, and adrenaline], and plays a central role in the neurotransmission and hormonal actions of CA. Thus, TH is related to various neuro-psychiatric diseases such as TH deficiency, Parkinson’s disease (PD), and schizophrenia. Four isoforms of human TH (hTH1–hTH4) are produced from a single gene by alternative… 
Tyrosine hydroxylase and regulation of dopamine synthesis.
Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation
The authors present the cryo-EM structures of full-length human TH in the apo form and bound with DA, as well as the structure of Ser40 phosphorylated TH, and discuss the inhibitory and stabilizing effects of DA on TH and its counteraction by Ser40-phosphorylation.
Tyrosine hydroxylase phosphorylation in vivo
This review on TH phosphorylation in vivo has three main sections focusing on: the methods used to investigate TH phosphate levels in vivo, the animals used, the sacrifice procedures, the tissue preparation, the measurement of TH protein levels and THosphorylation and the measurements of TH activation.
Tyrosine hydroxylase (TH), its cofactor tetrahydrobiopterin (BH4), other catecholamine-related enzymes, and their human genes in relation to the drug and gene therapies of Parkinson’s disease (PD): historical overview and future prospects
The historical overview of TH, BH4-, and other CA-related enzymes and their genes in relation to the pathophysiology of PD, the development of drugs, such as l-DOPA, and future prospects for drug and gene therapy for PD are discussed, especially the potential of induced pluripotent stem (iPS) cells.
Covalent modification and inhibition of tyrosine hydroxylase by 3,4-dihydroxyphenylacetaldehyde, an endogenously produced neurotoxin relevant to Parkinson's disease
It was hypothesized that DOPAL modifies and inhibits TH, and how it may play a role in the onset and progression of PD was of interest.
Chapter 14 – Catecholamines
Tyrosine hydroxylase gene: another piece of the genetic puzzle of Parkinson's disease.
The latest evidence on tyrosine hydroxylase genetic variants in PD is summarized, including the ongoing effort of using whole exome sequencing to search for rare variants inPD patients.
Palm Fruit Bioactives augment expression of Tyrosine Hydroxylase in the Nile Grass Rat basal ganglia and alter the colonic microbiome
Palm Fruit Bioactives (PFB) significantly increased the levels of tyrosine hydroxylase in the brain of the Nile Grass rat (NGR), a novel and potentially significant finding, unique to PFB among known botanical sources.
The quaternary structure of human tyrosine hydroxylase: effects of dystonia‐associated missense variants on oligomeric state and enzyme activity
Investigation of the structure of isoform 1 of human TH and its dystonia‐associated missense variants in E. coli revealed that Arg‐410 and Asp‐467 are important for maintaining the stability and oligomeric structure of TH.


Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology.
The TH gene may prove useful in gene therapy to compensate for decreased levels of catecholamines in neurological diseases, for example, for supplementation of dopamine in Parkinson's disease and psychiatric diseases, such as affective disorders and schizophrenia.
It has now been possible to demonstrate that brain, adrenal medulla, and sympathetically innervated tissues contain a specific hydroxylase that catalyzes the conversion of L-tyrosine to dopa.
Catecholamines and Serotonin Are Differently Regulated by Tetrahydrobiopterin
The data showing that catecholaminergic, serotonergic, and NO systems were differently affected by BH4 starvation suggest the possible involvement of BH 4 synthesis in the etiology of monoamine-based neurological and neuropsychiatric disorders.
Crystal structure of tyrosine hydroxylase at 2.3 Å and its implications for inherited neurodegenerative diseases
The structure provides a rationale for the effect of point mutations in TyrOH that cause L-DOPA responsive parkinsonism and Segawa's syndrome.
Tetrahydrobiopterin shows chaperone activity for tyrosine hydroxylase
It is shown that both the cofactor (6R)‐l‐erythro‐5,6,7,8‐tetrahydrobiopterin (BH4) and the feedback inhibitor and catecholamine product dopamine increase the kinetic stability of human TH isoform 1 in vitro.
The catecholamine system in health and disease —Relation to tyrosine 3-monooxygenase and other catecholamine-synthesizing enzymes—
  • T. Nagatsu
  • Biology
    Proceedings of the Japan Academy. Series B, Physical and biological sciences
  • 2007
Catecholamines [dopamine, noradrenaline (norepinephrine), and adrenaline (epinephrine); CAs] are neurotransmitters in the central and peripheral nervous systems as well as hormones in the endocrine
Dopamine Inhibition of Human Tyrosine Hydroxylase Type 1 Is Controlled by the Specific Portion in the N‐Terminus of the Enzyme
Observations suggest that the amino acid sequence Gly36‐Arg37‐Arg38 plays a key role in determining the competition between dopamine and 6RBPH4 and affects the efficiency of dopamine inhibition of the catalytic activity.
Regulation of N-terminus-deleted human tyrosine hydroxylase type 1 by end products of catecholamine biosynthetic pathway
It is suggested that the three catecholamine end products exert their inhibition on tyrosine hydroxylase to the same extent and that the N-terminal 52 amino acid residues contain the key sequence in mediating the inhibitory action.
RNAi of 14-3-3eta protein increases intracellular stability of tyrosine hydroxylase.
The 14-3-3 protein affects the conformation of the regulatory domain of human tyrosine hydroxylase.
Investigation of the conformation of the regulatory domain of human TH isoform 1 (TH1R) found that TH1R is an unstructured protein with a low content of secondary structure and that neither phosphorylation nor the 14-3-3 protein binding changes its secondary structure.