Modulation by basic polypeptides of ATP-induced activation of tyrosine hydroxylase prepared from bovine adrenal medulla.
The effects of basic polypeptides on the activation of adrenal tyrosine hydroxylase by ATP were investigated to show a possible involvement of macromolecular cell components in the regulation of the enzyme activity. Basic polypeptides caused an enhancement of the activation of tyrosine hydroxylase by low concentrations of ATP, and the potentiating effects of these polypeptides were observed to be dependent on their concentrations. Kinetic studies showed that basic polypeptides caused an increase in the Vmax of the ATP-activated enzyme for the cofactor without any change in the Km. These results suggest that basic polypeptides convert the enzyme from a nonsusceptible form to a form susceptible to ATP, thus resulting in the potentiation of the ATP-induced activation. Furthermore, the activation by ATP of tyrosine hydroxylase was not observed after treatment of the enzyme preparation with CM-cellulose, and the responsiveness of the enzyme treated with CM-cellulose to ATP was partially restored by addition of basic polypeptides. These observations suggest the possibility that macromolecular cell components, presumably basic proteins, may be involved in the regulation of the activity of tyrosine hydroxylase through their modulating effects on the sensitivity of the enzyme to ATP within the cell.