Activation and inactivation of striatal tyrosine hydroxylase: the effects of pH, ATP and cyclic AMP, S-adenosylmethionine and S-adenosylhomocysteine.

The activity of tyrosine hydroxylase (TH) in the corpus striatum of haloperidol treated and control rats has been examined. The activation of TH by haloperidol caused a decrease in the Km for tetrahydrobiopterin but no change in the Vmax. This effect was totally abolished when homogenates were prepared at high values of pH. A similar activation could be produced in vitro by preincubating with S-adenosylmethionine; conversely, enzyme activity was reduced by preincubating with S-adenosylhomocysteine. ATP and cyclic AMP activated the enzyme when incubated together with TH in vitro but the activity was reduced when the enzyme was preincubated with these substances. A possible role for carboxymethylation in controlling tyrosine hydroxylase activity is discussed.