Dopamine ^-hydroxylase is a copper-containing enzyme involved in the synthesis of the catecholamines noradrenaline and adrenaline from tyrosine in the adrenal medulla and central nervous system (see Figure 13.4). The active enzyme contains Cu+, which is oxidized to Cu2+ during the hydroxylation of the substrate. Reduction back to Cu+ specifically requires ascorbate, which is oxidized to monodehydroascorbate.
In intact adrenal medullary chromaffin cells in culture, the amount of noradrenaline formed is considerably greater than the amount of ascorbate present, and there is little or no detectable loss of ascorbate with enzyme action. However, in isolated chromaffin granules, there is stoichiometric oxidation of
ascorbate and hydroxylation of dopamine. The small pool of ascorbate in the granules is maintained by a transmembrane electron transport system (probably involving cytochrome b56i), at the expense of the considerably larger cy-tosolic pool of ascorbate. In turn, cytosolic monodehydroascorbate is reduced by monodehydroascorbate reductase in the outer mitochondrial membrane. This is an NADH-dependent enzyme; therefore, overall, the tissue shows stoichiometric oxidation of NADH with dopamine hydroxylation, although it is ascorbate that is the immediate electron donor (Diliberto et al., 1982; Menniti etal., 1986).
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