Tyrosine hydroxylase and regulation of dopamine synthesis

S. Colette Daubner, Tiffany Le, Shanzhi Wang

Research output: Contribution to journalArticle

279 Citations (Scopus)

Abstract

Tyrosine hydroxylase is the rate-limiting enzyme of catecholamine biosynthesis; it uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to DOPA. Its amino terminal 150 amino acids comprise a domain whose structure is involved in regulating the enzyme's activity. Modes of regulation include phosphorylation by multiple kinases at four different serine residues, and dephosphorylation by two phosphatases. The enzyme is inhibited in feedback fashion by the catecholamine neurotransmitters. Dopamine binds to TyrH competitively with tetrahydrobiopterin, and interacts with the R domain. TyrH activity is modulated by protein-protein interactions with enzymes in the same pathway or the tetrahydrobiopterin pathway, structural proteins considered to be chaperones that mediate the neuron's oxidative state, and the protein that transfers dopamine into secretory vesicles. TyrH is modified in the presence of NO, resulting in nitration of tyrosine residues and the glutathionylation of cysteine residues.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalArchives of Biochemistry and Biophysics
Volume508
Issue number1
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

Fingerprint

Tyrosine 3-Monooxygenase
Dopamine
Enzymes
Catecholamines
Tyrosine
Proteins
Nitration
Phosphorylation
Molecular oxygen
Biosynthesis
Secretory Vesicles
Enzyme activity
Phosphoric Monoester Hydrolases
Serine
Neurons
Cysteine
Neurotransmitter Agents
Phosphotransferases
Oxygen
Feedback

Keywords

  • α-synuclein
  • 14-3-3 protein
  • Dopamine biosynthesis
  • Protein glutathionylation
  • Protein kinases
  • Protein nitration
  • Protein-protein interactions
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Tyrosine hydroxylase and regulation of dopamine synthesis. / Daubner, S. Colette; Le, Tiffany; Wang, Shanzhi.

In: Archives of Biochemistry and Biophysics, Vol. 508, No. 1, 01.04.2011, p. 1-12.

Research output: Contribution to journalArticle

Daubner, S. Colette ; Le, Tiffany ; Wang, Shanzhi. / Tyrosine hydroxylase and regulation of dopamine synthesis. In: Archives of Biochemistry and Biophysics. 2011 ; Vol. 508, No. 1. pp. 1-12.
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