title: Comparison of dopamine beta-hydroxylase activity in normal rat adrenal medulla and rat pheochromocytoma cells.
abstract: Dopamine beta-hydroxylase activity is reportedly negligible in malignant rat adrenal cell lines. However, in two pheochromocytoma cell lines, PC12 and PCG2, considerable amounts of this catecholamine enzyme exist but its characteristics differ from the enzyme found in normal rat tissue in two ways. First, in normal adrenal medullary tissue, dopamine beta-hydroxylase activity increases linearly with increasing protein concentration. Second, there is a stringent requirement for copper. Concentrations of copper above or below the optimum inhibit enzymatic activity. In contrast, in pheochromocytoma cells, dopamine beta-hydroxylase exhibits a sigmoidal response with increasing tissue content. At dilute protein concentrations where considerable dopamine beta-hydroxylase activity is observed in normal adrenal medullary extracts, enzymatic activity is negligible in the pheochromocytoma cell lines. As the protein concentration is increased, activation of the enzyme occurs, and enzymatic activity increases linearly with further increases in protein concentration. At very high concentrations of protein, enzymatic activity plateaus. For both PC12 and PCG2 cells, dopamine beta-hydroxylase activity shows minimal copper dependency, suggesting that endogenous inhibitors present in normal tissue are absent in these malignant cell lines. Under conditions of maximum activation, the activity of the enzyme in PC12 cells becomes equivalent to that in normal rat adrenal medulla but remains 45-fold greater than that in PCG2 cells.
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000201:enzymology*; D000313:Adrenal Medulla / Q000201:enzymology*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002999:Clone Cells; D003300:Copper / Q000502:physiology; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism*; D010673:Pheochromocytoma; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D003300:Copper; D004299:Dopamine beta-Hydroxylase