A model mechanism of nitric oxide (NO) formation by NO synthase

The recent discovery that nitric oxide (NO) plays a role as a second messen ger in biological processes created a growing interest in this radical. NO is synthesized from one of the terminal nitrogen atom of L-arginine by the action of the NO synthase (NOS). The NOS catalyze a five-electron oxidation of L-Arg. We thus propose a reaction mechanism based on the experimental d ata. Thus, N-methyl guanidine was used as a model compound for Arginine to study the mechanism of oxidative release of NO by means of ab initio molecu lar computations. The oxidation of this model compound was carried out with the aid of performic acid. In this model mechanism, the released specie is HNO, which can easily form NO. From the values obtained from HOMO-LUMO ene rgy differences, it is clear that the peracid is being reduced, i.e. it is gaining an electron pair and is accommodating that on its HOMO, while L-Arg is being oxidized. This hypothesis is supported by the net charge at the n itrogen atom of guanidine, which undergoes oxidation. On the whole, the rea ction mechanism proposed provides a negative Gibbs free energy (-7.33 kcal mol(-1)), suggesting that the reaction is thermodynamically feasible. The r eaction mechanism confirmed the previous hyphotesis about the origin of the NO, from the oxidized nitrogen of the guanidine group, and the weakening o f the C-3-N-4 bond that leads to the final product of the second oxidation: HNO. Our results fully agree with the previous experimental findings. (C) 1999 Elsevier Science B.V. All rights reserved.