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Pharm Res. 2006 Aug;23(8):1702-11.

Kinetic modeling of nitric-oxide-associated reaction network.

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  • 1School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China. tmhu@ndmctsgh.edu.tw

Abstract

PURPOSE:

Nitric oxide and superoxide are the two important free radicals in the biological system. The coexistence of both free radicals in the physiological milieu gives rise to intricate oxidative and nitrosative reactions, which have been implicated in many physiological and/or pathophysiological conditions, such as vasodilatation and inflammation. It is difficult, if not impossible, to study the complexity of the nitric oxide/superoxide system using current experimental approaches. Computational modeling thus offers an alternative way for studying the problem.

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 N203, GSNO and GSH are sensitive to the variation of basal GSH levels. The kinetics of the potential nitrosative species, N203, 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 N203 mediated nitrosation reaction.

[PubMed - indexed for MEDLINE]
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