Tyrosine hydroxylase and regulation of dopamine synthesis

S. Colette Daubner, Tiffany Le, Shanzhi Wang

Research output: Contribution to journalReview article

288 Scopus citations

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

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Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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