Stability Properties of Activated Tryptophan Hydroxylase from Rat Midbrain

Abstract
Time courses of the activation-inactivation sequence in rat midbrain tryptophan hydroxylase after preincubation with Ca, ATP + MgCl2 or sulfhydryl reagents and after freezing and thawing suggest that the activated enzyme is more vulnerable to loss of activity. The sequence induced by Ca was prevented by the protease inhibitor leupeptin, and an accelerated decline in activity after activation by ATP + MgCl2 was reduced greatly by increasing levels of tetrahydrobiopterin (BH4) cofactor. The effects of Ca and ATP + MgCl2 were additive, which suggests independent mechanisms. The time courses of enzyme activation and inactivation processes may offer a useful way to study the influence of a range of effectors on tryptophan hydroxylase function.