Dopamine (DA) availability for precursor function and peripheral
biological action is dependent on synthesis and inactivation
enzymes, most of them have been cloned and located. An aromatic
acid decarboxylase (AADC) defect has been reported in male homozygotic twins. The syndrome of complete
dopamine-beta-hydroxylase deficiency with
orthostatic hypotension and very high DA contributes to our understanding of the role of DA as a
catecholamine with a peripheral
biological action of its own. X-linked isolated
monoamine oxidase A gene deficiency represents a marked disturbance of monoamine metabolism. The genes of the two major extraneuronal DA-metabolizing
enzymes--
catechol-O-methyl-
transferase and phenolsulfotransferase (PST)-have also been defined. Of particular interest is a bidirectional shuttle system between the PST and
sulfatase which have been cloned and located. DA, highly sulfoconjugated via PST, yields DA
sulfate which is reconvertible by
sulfatase to Free DA. A defect of
sulfatase catalyzing this process results in a predominance of DA as biologically inactive DA
sulfate and so attenuates the DA action. Enzymatic defects of DA synthesis and metabolism are thus genetic modulators of DA action.