There are times when dopamine1 concentrations rise in the synaptic space (or even inside the terminal). When this happens, the dopamine can be oxidized by O2 without the help of any enzyme2. This is called “autooxidation”. The drug3 methamphetamine4 is a good example to describe how autooxidation of dopamine gets started and how cells undergo oxidative damage. Methamphetamine, like amphetamine, is a central nervous system stimulant5. It causes the release of dopamine from the axon terminal into the space between the neurons (the synaptic space). The excess dopamine in the synaptic space binds to dopamine receptors6 on specific neurons to cause stimulation of certain pathways in the brain, resulting in increased alertness and agitation. With repeated use of methamphetamine or when high doses are used, dopamine accumulates in the synaptic space because the dopamine transporters become saturated; they are not able to transport the dopamine back inside the terminal very efficiently. The excess dopamine then becomes autooxidized by O2 present in the extracellular space, without the help of any enzymes. However, the autooxidation of dopamine occurs at the other end of the dopamine molecule (on the ring) compared to enzyme-catalyzed oxidation7. The reaction for autooxidation of dopamine is shown in Figure 4.
Figure 4 Dopamine is oxidized by O2 alone to form a quinone and the superoxide radical. This can occur in the synaptic space or inside the terminal.
Definitions:
1 a neurotransmitter stored in vesicles of nerve terminals; it is a monoamine that is easily oxidized. This neurotransmitter is contained in neuron pathways important in brain stimulation, addiction and control of movement.
2 a protein that catalyzes the rate at which a reaction occurs. It binds to one of the reactants (a substrate) to cause a change in the reactant’s structure, facilitating the reaction.
3 a substance that affects the structure or function of a cell or organism.
4 a derivative of amphetamine that increases the release of dopamine into the synaptic space. It causes increased alertness, restlessness and agitation.
5 a compound that activates certain pathways in the brain to increase alertness and decrease fatigue.
6 a protein to which hormones, neurotransmitters and drugs bind. They are usually located on cell membranes and elicit a function once bound.
7 the donation of electrons to another atom often by removal of a H+ atom.
