Dopamine Metabolism and Reactive Oxygen Species Production

Due to their chemical nature, dopamine and its metabolites are easily oxidized—a process often accompanied by the production of reactive oxygen species. While the MAO-mediated degradation of dopamine leads to the formation of hydrogen peroxide, the autoxidation of many intermediates of dopamine metabolism produces highly reactive quinones. These quinones can bind to cysteinyl residues of reduced GSH or proteins, leading to their inactivation if this residue is located in the active site of a protein. One way to overcome this problem is to increase production or
uptake of antioxidants such as GSH or ascorbate. Interaction with astrocytes is an important fact for dopaminergic neuron survival: astrocytes provide the neurons with the GSH-precursor glutamine and are able to degrade excessive dopamine released by neurons. In dopaminergic neurons, excessive amounts of catecholamines can also be inactivated by their polymerization to neuromelanin. This polymer pigment itself can, however, have both a protective or deleterious effect, depending on the cellular context. It should be noted that although l-DOPA still represents the state-of-the-art treatment for Parkinson’s disease, it also represents a catecholamine that can contribute to oxidative stress in already damaged dopaminergic neurons. Oxidative damage
outside the brain induced by longtime l-DOPA treatment (e.g., in melanocytes) has often been discussed; however, there is little clinical evidence for that theory. Finally, dopamine metabolism can be altered by genetic factors such as tyrosine hydroxylase deficiency or genetic variants of the dopamine transporter, as well as environmental factors such as pesticides or drugs.