Regulation of the synthesis of choline-O-acetyltransferase and thymidylate synthetase in mouse neuroblastoma in cell culture.

The specific activity of mouse neuroblastoma choline-O-acetyltransferase (EC 2.3.1.6.) increased 5.7-fold when the rate of cell division was restricted (as compared to cells kept rapidly dividing for 9 days); the specific activity of mouse neuroblastoma thymidylate synthetase increased 2.4-fold when nondividing cells again entered the logarithmic phase of cell growth. The highest specific activities for choline-O-acetyltransferase and lowest specific activities for thymidylate synthetase were obtained from cultures where cell division was restricted; the opposite result was observed when the cells were growing rapidly. Thus, the regulation of these two enzymes is out of phase with respect to each other and is dependent on the rate of cell division. The inverse relationship for the regulation of these two enzymes is discussed in relation to the needs of mitotic versus differentiated neuroblastoma cells.