Mechanisms of Interaction of Nitric Oxide (NO) and its Metabolites with Enzymes Responsible for the Physiological Effects of NO

Vladimir   Yu.   Titov

Abstract

It is known that nitric oxide (NO) realizes its basic physiological effects by affecting activity of specific enzymes, such as guanylate cyclase and caspase. Since NO itself in physiological conditions is a short-lived substance, it is considered that it acts by means of some metabolites such as nitrosothiols and some nitro-compounds, which may serve as NO - donors. These NO metabolites are relatively stable substances and their concentrations in biological tissues are also relatively stable. But in this case it is unclear how their physiological effects are controlled. Could they, for example, respond to the certain factors, be accumulated in the right place at the right time or just dissociate releasing NO? In scientific literature these questions remain unanswered. In this review we present the result of our analysis of the available scientific data from the different researchers on the interaction of some NO-donors with guanylate cyclase, caspase and catalase. We propose that NO-like effects of these NOdonors are not the result of only their simple dissociation with releasing of NO. Mostly it is a complex process that starts with initial transformation of these substances into nitrosyl-iron complexes. NO-group of this complex becomes available for the interaction as nitrosation agent only at the moment of destabilization of the complex, which can be initiated by variation of iron associated ligands included in the complex. The ligand content in the medium can be changed depending on physiological conditions.

Keywords: Nitric oxide, nitroso- and nitro, –, compounds, guanylate cyclase, caspase, catalase

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