Mechanisms of the Formation and Function of Dinitrosyl Iron Complexes as a “Working Form” of Nitric Oxide in Living Organisms

Abstract

The thesis is proposed that only the inclusion of endogenous nitric oxide (NO) in living organisms in dinitrosyl iron complexes or in S-nitrosothiols can provide its stabilization, which is necessary for the functioning of NO as both an auto- and paracrine regulator of metabolic processes. Without such inclusion, the nearly all the endogenous NO disappears due to the aggressive action of the intracellular and extracellular medium of the body on it and is thereby excluded from processes of vital activity. The introduction of exogenous NO into the body of animals and humans (possible only by inhalation of its gaseous form) does not lead to the formation of either dinitrosyl iron complexes or S-nitrosothiols in blood and other tissues. In this case, the nearly all the exogenous NO is converted in the blood into nitrosonium (NO⁺) cations, the appearance of which is evidenced by their conversion into S-nitrosothiols under simultaneous inhalation of exogenous NO with the introduction of various thiols into the blood of animals. As well, the appearance of S-nitrosothiols in these animals is detected by their hypotensive effect on animals. The conversion of NO into nitrosonium cations also occurs during the synthesis of dinitrosyl iron complexes, as caused in living organisms by the reaction of disproportionation of endogenous NO molecules that bind in pairs with ferrous ions. The subsequent binding of Fe(NO)₂ groups arising during this reaction with thiol-containing ligands leads to the formation of sufficiently stable dinitrosyl iron complexes that function in living organisms as donors of both neutral NO molecules and nitrosonium (NO⁺) cations. The transfer of the latter to the targets of their biological effects is carried out as a result of direct contact of low-molecular-weight dinitrosyl iron complexes, respectively, with the heme group of heme-containing proteins (for example, guanylate cyclase) or with thiol groups of low molecular weight and protein thiol-containing compounds. Various consequences of such NO and NO⁺ transfer in living organisms are presented, which are both positive, regulatory, and negative, toxic.