Why Does not Oxygen as an Oxidizer of Nitric Oxide Eliminate it from the Human and Animals' Organism? (The Role of EPR-Active Dinitosyl Iron Complexes with Thiol-Containing Ligands in the Preservation of Nitric Oxide in These Organisms)
摘要
It has been shown that the preservation of nitric oxide (NO) in the tissues of animal and human organs, despite the presence of a significant amount (up to several millimoles) of oxygen (O2) as an oxidizer of NO, can be due to two reasons. The first, trivial one is determined by the low rate of NO oxidation by oxygen at its concentration of less than 10 μM, at which the remaining amount of NO is sufficient to implement its biological effect, for example, the ability to exert a vasodilatory effect on blood vessels. At NO concentrations of 50 μM or more, for example, in activated macrophages, an increase in the NO oxidation rate can sharply decrease the NO concentration in macrophages and thereby weaken their immune activity. In this case, NO oxidation is prevented by its inclusion in EPR-active dinitrosyl iron complexes (DNICs) with thiol-containing ligands. The formation of these complexes is determined by the competitive inclusion of a divalent weakly bound ("free") iron ion instead of an oxygen molecule into the dimeric form of NO, as a target for the oxidative action of oxygen on NO. The inclusion of NO in DNICs not only stabilizes NO, but also leads to the transformation of half of it in these complexes into nitrosonium cations (NO+). As a result, DNICs with thiol-containing ligands can act in the body of animals and humans not only as donors of NO molecules as positive regulators of various metabolic processes, but also as NO+ cations as negative, cytotoxic agents.