Tyrosine hydroxylase is inactivated by catechol-quinones and converted to a redox-cycling quinoprotein

Possible relevance to Parkinson's disease

Donald M. Kuhn, Robert E. Arthur, David M. Thomas, Lisa Elferink

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Quinone derivatives of DOPA, dopamine, and N-acetyldopamine inactivate tyrosine hydroxylase, the initial and rate-limiting enzyme in the biosynthesis of the catecholamine neurotransmitters. The parent catechols are inert in this capacity. The effects of the catechol-quinones on tyrosine hydroxylase are prevented by antioxidants and reducing reagents but not by scavengers of hydrogen peroxide, hydroxyl radicals, or superoxide radicals. Quinone modification of tyrosine hydroxylase modifies enzyme sulfhydryl groups and results in the formation of cysteinyl-catechols within the enzyme. Catechol-quinones convert tyrosine hydroxylase to a redox-cycling quinoprotein. Quinotyrosine hydroxylase causes the reduction of the transition metals iron and copper and may therefore contribute to Fenton-like reactions and oxidative stress in neurons. The discovery that a phenotypic marker for catecholamine neurons can be converted into a redox-active species is highly relevant for neurodegenerative conditions such as Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)1309-1317
Number of pages9
JournalJournal of Neurochemistry
Volume73
Issue number3
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Quinones
Tyrosine 3-Monooxygenase
Oxidation-Reduction
Parkinson Disease
Catechols
Neurons
Catecholamines
Enzymes
Oxidative stress
Biosynthesis
Mixed Function Oxygenases
Superoxides
Hydroxyl Radical
Hydrogen Peroxide
Transition metals
Neurotransmitter Agents
Copper
Dopamine
Oxidative Stress
Iron

Keywords

  • DOPA
  • Dopamine
  • Quinones
  • Quinoproteins
  • Redox-cycling
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Tyrosine hydroxylase is inactivated by catechol-quinones and converted to a redox-cycling quinoprotein : Possible relevance to Parkinson's disease. / Kuhn, Donald M.; Arthur, Robert E.; Thomas, David M.; Elferink, Lisa.

In: Journal of Neurochemistry, Vol. 73, No. 3, 1999, p. 1309-1317.

Research output: Contribution to journalArticle

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