Neuronal nitric oxide synthase: Prototype for pulsed enzymology

Abstract 

The established paradigm in understanding and describing enzyme activity uses formalisms based on steady-state assumptions, including Michaelis–Menten and King–Altman approaches. These are appropriate for enzymes operating under steady-state conditions. Signal generating enzymes transfer information, rather than material. Because the information capacity of a signal channel depends on frequency, steady-state descriptions may not be appropriate. Recently, Stuehr and coworkers described a novel product inhibition mechanism for NO synthases. Simulations presented here suggest that at physiological temperatures neuronal nitric oxide synthase produces sharp pulses of NO, consistent with its signaling function. These temporal pulses greatly restrict the effective spatial range of NO signaling.

Abbreviations: ¹NADPH, nicotinamide adenine dinucleotide phosphate, ²iNOS, inducible nitric oxide synthase, ³eNOS, endothelial nitric oxide synthase, ⁴NOS, nitric oxide synthase, ⁵nNOS, neuronal nitric oxide synthase, ⁶CaM, calmodulin, ⁷CNS, central nervous system

Keywords: Pulsed, Enzyme, Signaling, Feedback, Nitric oxide, Kinetics