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Tyrosine Hydroxylase Is Inactivated by Catechol‐Quinones and Converted to a Redox‐Cycling Quinoprotein
Author(s) -
Kuhn Donald M.,
Arthur Robert E.,
Thomas David M.,
Elferink Lisa A.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731309.x
Subject(s) - tyrosine hydroxylase , chemistry , tyrosine , hydrogen peroxide , tyrosine 3 monooxygenase , enzyme , quinone , redox , biochemistry , catechol , catecholamine , superoxide , dopamine , oxidative phosphorylation , biology , organic chemistry , neuroscience
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 catecholquinones 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. Catecholquinones 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.