Space, time and nitric oxide--neuronal nitric oxide synthase generates signal pulses.

The temporal aspects of signaling are critical to the function of signals in communications, feedback regulation and control. The production and transduction of biological signals by enzymes comprises an area of central importance and rapid progress in the biomedical sciences. Treatment of signaling enzymes almost universally employs steady-state analyses that are suitable for mass catalysis but inappropriate for components in an information channel or a feedback/control system. In the present study, we show that, at 37 degrees C, neuronal nitric oxide synthase (EC 1.14.13.39) is progressively inhibited by the formation of an inhibited state during the first few turnovers (approximately 200 ms) after the initiation of catalysis, leading to pulse formation of nitric oxide. The general mechanism may be of wide importance in biological signaling.