Calcium-dependent activation of tryptophan hydroxylase by ATP and magnesium

Tryptophan hydroxylase EC 1.14.16.4; L-tryptophan, tetrahydropteridine: oxygen oxidoreductase (5-hydroxylating)] in rat brainstem extracts is activated 2 to 2.5-fold by ATP and Mg⁺⁺ in the presence of subsaturating concentrations of the cofactor 6-methyltetrahydropterin (6MPH₄). The activation of tryptophan hydroxylase under these conditions results from a reduction in the apparent K_m for 6MPH₄ from 0.21 mM to 0.09 mM. The activation requires Mg⁺⁺ and ATP but is not dependent on either cAMP or cGMP. The effect of ATP and Mg⁺⁺ on enzyme activity was enhanced by μM concentrations of Ca⁺⁺ and totally blocked by EGTA. These data suggest that tryptophan hydroxylase can be activated by a cyclic nucleotide independent protein kinase which requires low calcium concentrations for the expression of its activity.