Tyrosine hydroxylase is inactivated by catechol-quinones and converted to a redox-cycling quinoprotein: possible relevance to Parkinson's disease.
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.
Kuhn
D M
DM
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Arthur
R E
RE
Thomas
D M
DM
Elferink
L A
LA
D000818:Animals; D002396:Catechols / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004295:Dihydroxyphenylalanine / Q000737:chemistry; D004298:Dopamine / Q000031:analogs & derivatives / Q000737:chemistry; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006868:Hydrolysis; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000201:enzymology; D011809:Quinones / Q000737:chemistry; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D002396:Catechols; D004791:Enzyme Inhibitors; D011809:Quinones; C006374:N-acetyldopamine; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine