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

M. B. Santillán, G. M. Ciuffo, E. A. Jáuregui, I. G. Csizmadia

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The recent discovery that nitric oxide (NO) plays a role as a second messenger 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 data. 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 molecular 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 energy 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 nitrogen atom of guanidine, which undergoes oxidation. On the whole, the reaction mechanism proposed provides a negative Gibbs free energy (-7.33 kcal mol-1), suggesting that the reaction is thermodynamically feasible. The reaction mechanism confirmed the previous hyphotesis about the origin of the NO, from the oxidized nitrogen of the guanidine group, and the weakening of the C3-N4 bond that leads to the final product of the second oxidation: HNO. Our results fully agree with the previous experimental findings.

Original languageEnglish
Pages (from-to)223-239
Number of pages17
JournalJournal of Molecular Structure: THEOCHEM
Issue number3
Publication statusPublished - Aug 20 1999



  • Ab initio study
  • Nitric oxide
  • Reaction mechanism
  • Thermodynamics

ASJC Scopus subject areas

  • Biochemistry
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

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