A pterin is found in vegetables that contain pigments, like carrots, =
tomatoes, and
sweet potatoes.
[Journal of Neurochemistry] [JNC Home=
Page]
[Search Tables of Con=
tents]
Generation of Reactive Oxygen Species by Tyrosine Hydroxylase: A Poss=
ible
Contribution to the Degeneration of Dopaminergic Neurons?
Jan Haavik, Bj=F8rg Alm=E5s, and Torgeir Flatmark
Department of Biochemistry and Molecular Biology, University of Berge=
n,
Bergen, Norway
It has been suggested that idiopathic parkinsonism, characterized by =
a loss
of dopaminergic neurons of the nigrostriatal pathway, is due to the
intracellular generation of reactive oxygen species, generated by a
nonenzymatic or enzymatic partial reduction of dioxygen. Based on in =
vitro
studies of the iron-containing monooxygenase tyrosine hydroxylase (TH=
),
evidence is presented that this enzyme system may also contribute to =
such an
oxidative stress. Thus, the purified and Fe2+-reconstituted recombina=
nt
human enzyme shows a time- and temperature-dependent partial uncoupli=
ng of
the hydroxylation of L-tyrosine with the natural cofactor
(6R)-tetrahydrobiopterin, resulting in the formation of H2O2. The deg=
ree of
uncoupling of the hydroxylation reaction is significantly higher when
certain substrate analogues, notably the 7-substituted isomer
(7-tetrahydrobiopterin) of the natural cofactor, is used. In the pres=
ence of
H2O2 and Fe2+, the addition of TH increases the production of the hig=
hly
reactive =B7OH radical, probably via a Fenton type of reaction. It is=
not
clear whether this in vitro reaction can mediate cellular injury in v=
ivo.
However, it is known that the distribution of TH in the central and
peripheral nervous system often corresponds to that of the neuronal
degeneration in idiopathic parkinsonism, a finding that is compatible=
with a
pathogenetic effect of TH.
Key Words: Tyrosine hydroxylase-Oxidative stress-Reactive oxygen
species-Neurodegeneration-Parkinson's disease-Dopaminergic neurons.
J. Neurochem. 68, 328-332 (1997).
