Activation of brain tryptophan hydroxylase by ATP-MG2+: dependence on calmodulin.

Open Access
Publisher Website
Google Scholar
Abstract
Tryptophan hydroxylase [from rat brain] is activated by phosphorylating conditions (ATP-Mg2+) in a Ca-dependent, cAMP-independent manner. Addition to the phosphorylation reaction of certain antipsychotic drugs that bind to calmodulin, the heat-stable Ca-binding protein, prevents the activation of tryptophan hydroxylase by ATP-Mg2+ in a concentration-dependent fashion. External addition of purified calmodulin protects the enzyme from the drug-induced effects. Calmodulin-free tryptophan hydroxylase prepared by affinity chromatography on fluphenazine-Sepharose is not activated by ATP-Mg2+ whereas addition of calmodulin to calmodulin-free enzyme restores the responsiveness of the hydroxylase to ATP-Mg2+ only in the presence of Ca2+. The activation of tryptophan hydroxylase by phosphorylating conditions is apparently dependent on both Ca and calmodulin.