Dopamine -monooxygenase, properties

Tyrosinase is a monooxygenase which catalyzes the incorporation of one oxygen atom from dioxygen into phenols and further oxidizes the catechols formed to o-quinones (oxidase action). A comparison of spectral (EPR, electronic absorption, CD, and resonance Raman) properties of oxy-tyrosinase and its derivatives with those of oxy-Hc establishes a close similarity of the active site structures in these proteins (26-29). Thus, it seems likely that there is a close relationship between the binding of dioxygen and the ability to "activate" it for reaction and incoiporation into organic substrates. Other important copper monooxygenases which are however of lesser relevance to the model studies discussed below include dopamine p-hydroxylase (16,30) and a recently described copper-dependent phenylalanine hydroxylase (31). 

MPTP is also metabolized by other routes involving cytochromes P-450, FAD-dependent monooxygenases, and aldehyde oxidase. However, these seem to be detoxication pathways, as they divert MPTP away from uptake and metabolism in the brain. However, MPTP may inhibit its own metabolism by cytochromes P-450 and thereby reduce one means of detoxication. This example illustrates the importance of structure and physicochemical properties in toxicology. MPTP is sufficiently lipophilic to cross the blood-brain barrier and gain access to the astrocytes. The structure of the metabolite is important for uptake via the dopamine system, hence localizing the compound to a particular type of neuron. Again, uptake into mitochondria is presumably a function of structure, as a specific energy-dependent carrier is involved. 

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