Activation of midbrain tryptophan hydroxylase by MgATP. Absence during early postnatal development.

Abstract

The brain tryptophan hydroxylase is known to be activated by magnesium adenosine triphosphate (MgATP). This activation has been suspected to be a case of enzyme phosphorylation, although convincing evidence is still lacking. In supernatants (100,000 g) from adult mouse midbrains, the addition of 1 mM ATP and 10 mM MgCl2 could increase the tryptophan activity by 70-90%, when the enzyme activity was determined at a subsaturating concentration of 6-MPH4 (0.2 mM). The present study has revealed that the enzyme activation by MgATP could only be achieved from mice after 12 days of postnatal age. No activation was found in midbrain preparations from younger animals, although a substantial level of tryptophan hydroxylase activity was already present. The possibility that some required component(s) for the enzyme activation may be lacking during early development was tested by mixing a dialyzed adult preparation with the neonatal midbrain supernatant. Under these conditions, the tryptophan hydroxylase in the neonatal supernatant was activated by MgATP. Furthermore, the addition of a crude protein kinase fraction from adult midbrain cytosol was also capable of restoring the enzyme activatability in the neonatal preparation. It appears that the lack of activatability by MgATP alone during early development was due to absence of one or more biochemical factors required for the activation.