Kinetic Modeling of Nitric-Oxide-Associated Reaction Network

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Abstract

Methods

In this present study, key reaction pathways related to the generation, reaction and scavenging of both nitric oxide and superoxide were integrated into a reaction network. The network dynamics was investigated by numerical simulations to a set of coupled differential equations and by dynamical analysis. Two specific questions pertaining to the reaction kinetics of the reactive chemical species in the nitric oxide/superoxide system were studied: (1) how does the system respond dynamically when the generation rate of nitric oxide and superoxide varies? (2) how would antioxidants such as glutathione modulate the system dynamics?

Results

While changing basal GSH levels does not alter the kinetics of nitric oxide, superoxide, and peroxynitrite, the kinetic profiles of N2O3, GSNO and GSH are sensitive to the variation of basal GSH levels. The kinetics of the potential nitrosative species, N2O3, is switch like, which is dependent on the level of GSH.

Conclusions

The model predicts that concurrent high nitric oxide and superoxide generation–such as in the inflammatory conditions–may result in nonlinear system dynamics, and glutathione may serve as a dynamic switch of N2O3 mediated nitrosation reaction.

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