The generation of reactive
quinone species (
DAQ) from oxidation of
dopamine (DA) is involved in neurodegenerative pathologies like
Parkinson's disease (A. Borta, G. U. Höglinger, J. Neurochem. 2007, 100, 587-595). The oxidation of DA to
DAQ can occur either in a single two-electron process or in two consecutive one-electron steps, through
semiquinone radicals, giving rise to different patterns of reactions. The former type of reaction can be promoted by
tyrosinase, the latter by
peroxidases in the presence of H(2)O(2), which can be formed under oxidative stress conditions. Both
enzymes were employed for the characterization of the
thiol-
catechol adducts formed by reaction of DA and
cysteine or
glutathione, and for the identification of specific
amino acid residues modified by DAQs in two representative target
proteins, human and horse heart
myoglobin. Our results indicate that the cysteinyl-DA adducts are formed from the same
quinone intermediate independently of the mechanism of DA oxidation, and that the hallmark of a radical mechanism is the formation of the
cystine dimer. The reactivity of
quinone species also controls the DA-promoted derivatization of
histidine residues in
proteins. However, for the modification of the
cysteine residue in human
myoglobin, a radical intramolecular mechanism has been proposed, in which the
protein acts both as the catalyst and target of the reaction. Most importantly, the modification of myoglobins through
DAQ linkages, and in particular by DA oligomers, has dramatic effects on their stability, as it induces protein unfolding and incorporation into insoluble melanic precipitates.