Peroxynitrite: Toxic Agent and Signaling Molecule (Review)
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xynitrite: Toxic Agent and Signaling Molecule (Review) Yu. V. Abalenikhinaa, O. V. Kosmachevskayab, and A. F. Topunovb, * a
b
Pavlov Ryazan State Medical University, Ryazan, 390026 Russia Bach Institute of Biochemistry, Federal Research Center Fundamentals of Biotechnology, Russian Academy of Sciences, Moscow, 119071 Russia *e-mail: [email protected] Received May 5, 2020; revised June 10, 2020; accepted July 2, 2020
Abstract—Peroxynitrite, a reactive nitrogen species, is one of the strongest oxidants in the body. Depending on the conditions, it either undergoes biotransformation and detoxification or interacts with various compounds (proteins, including enzymes; lipids, nucleic acids, and carbohydrates) and modifies them. Thiols, including cysteine residues in proteins, are most actively exposed to peroxynitrite. The inhibitory effect of peroxynitrite on enzymes was best described for oxidoreductases, in which it also most often acted on cysteine. Modified biomolecules can be toxic; however, at physiological concentrations, they are able to function as members of signaling pathways. The described data show that peroxynitrite is not only a toxic agent but also a component of the messenger system and a signaling molecule responsible for the redox regulation of cellular metabolism. The detoxification pathways are important aspects in the study of peroxynitrite and may facilitate the search for medicinal agents against diseases accompanied by nitrosative stress. Keywords: peroxynitrite, peroxynitrous acid, nitric oxide, cysteine, toxic effect, signaling function DOI: 10.1134/S0003683820060022
INTRODUCTION A large number of chemical compounds function in living organisms; during metabolism, these compounds can play a diverse and, sometimes, directly opposite role. Thus, upon an increase in concentration, many antioxidants pass into the status of prooxidants, which should be taken into account in the description of their properties. It is also known that many compounds in the body under certain conditions can also perform a signaling function. These compounds include peroxynitrite; only its properties as a strong oxidizing agent are usually described. Peroxynitrite anion (ОNOO–) forms in vivo as a result of the reaction between nitric oxide (NO) and superoxide radical anion О•2− . Despite its short halflife (10 ms at physiological pH), ОNOO– is able to penetrate biological membranes both via passive diffusion and through anion channels. Peroxynitrite is the peroxynitrous acid (ONOOH) anion; therefore, the exchange of these two compounds is usually considered in a complex. After synthesis, ОNOO– can be removed by trap substances or undergo biotransformation to form nontoxic products and can act as a signaling molecule and a toxic agent. Further transformations of peroxynitrite, including biotransformation, detoxification, or interaction with targets, depend on the substrate availability and the
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environmental conditions of the cell. On the one hand, its exchange leads to the formation of toxic products, and, on t
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