Figure 1

Neuronal DA metabolism. In the neurite of DAergic neurons, DA is synthesized by combined action of TH and AADC and imported into synaptic vesicles by VMAT2. DA leaking from the vesicles is deaminated by MAO. Upon neuronal excitation DA is released into the synaptic cleft for signal transduction. DA signaling stops by reimport to the presynaptic neuron and recycling or by import to surrounding cells and degradation by COMT, MAO, AR, ADH and ALDH. The main DA degradation products are DOPAC and HVA. In cytoplasmic vesicles NM is built of DA oxidation products and other components and can chelate iron. DA or DOPA can be oxidized to their corresponding reactive quinones (Q) that react further on to form a variety of partly neurotoxic compounds and protein adducts. These toxins and the ROS generated from DA deamination can cause cell damage and neurodegeneration. See text and Figures 2, 4 and 5 for further details and references.