Tyrosine hydroxylase in neuroblastoma

Tyrosine hydroxylase activity was assayed in two neuroblastoma tissues. It was found that the neuroblastoma tyrosine hydroxylase required DMPH₄ as a cofactor and was stimulated by Fe²⁺. These properties are quite similar to those reported for bovine and pheochromocytoma enzymes.Catechol compounds and other inhibitors, at concentrations of 2.5 × 10⁻⁵-5 × 10⁻⁴m, inhibited the neuroblastoma enzyme to the same extent as bovine adrenal tyrosine hydroxylase. This finding suggests that neuroblastoma tyrosine hydroxylase is normally susceptible to feedback inhibition, in contrast to the pheochromocytoma enzyme which has been reported to be less sensitive to inhibition by catechols.Both neuroblastoma and pheochromocytoma are associated with increased synthesis of catecholamines; in the case of pheochromocytoma there are large stores of norepinephrine in the tumor, but catecholamine synthesis still continues at an elevated rate, apparently because of a decreased sensitivity to feedback inhibition of the tyrosine hydroxylase in this tumor. On the other hand, in neuroblastoma the catecholamines appear to exert a “normal” feedback inhibition on tyrosine hydroxylase, and, therefore, we must look elsewhere to explain the high rate of catecholamine synthesis, such as lowering of the intracellular catecholamine levels by rapid metabolism. Further investigation will be necessary to establish the alteration of control mechanisms in neuroblastoma.