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The Free-Radical Nature of Nitric Oxide Molecules as a Determinant of their Conversion to Nitrosonium Cations in Living Systems

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Abstract

This paper presents new results that confirm our previous inference that the binuclear form of biologically active dinitrosyl iron complexes (B-DNICs) with thiol-containing ligands (glutathione or N-acetyl-L-cysteine) may act as a donor of nitrosonium cations, which are responsible for S-nitrosothiol formation during B-DNIC decomposition in acid solutions under both aerobic and anaerobic conditions. The presence of nitrosonium cations within B-DNICs is determined by the dispropoportionation reaction of free-radical nitric oxide (NO) molecules while binding to Fe2+ cations (two molecules per one ion) during B-DNIC synthesis. When thiolic ligands are oxidized in DNICs or inactivated by thiol-specific reagents, the nitrosonium cations released during decomposition of these DNICs at neutral pH values are hydrolyzed and transformed to nitrite anions. A similar transformation occurs when mononuclear DNICs (M-DNICs) with nonthiolic ligands are decomposed at neutral pH values. It has been found that S-nitrosothiol formation in the decomposition of B-DNICs with thiolic ligands at acidic pH values can be inhibited by the presence of a two to threefold excess of free thiol molecules (outside the B-DNIC) with regard to the B-DNIC level. This inhibition is due to the reduction of nitrosonium cations induced by free thiol molecules and catalyzed by iron ions. The NO molecules that result from the reduction are released from the DNICs. Thus, both forms of DNICs, M and B, that form in living systems can act not only as donors of NO, which is now recognized as one of the universal regulators of metabolic processes, but also as donors of nitrosonium cations, which initiate S-nitrosation of low- and high-molecular-weight (protein-bound) thiols.

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ACKNOWLEDGMENTS

The author is grateful to V.D. Mikoyan for recording EPR spectra (Fig. 8), P.P. Borodulin for recording light absorbance spectra (Figs. 6 and 7), and N.A. Tkachev for computerized data processing (Figs. 4, 5, and 9).

Funding

This work was supported by the State Order of the Russian Federal Agency for Scientific Organizations, projects 00008202014-0001b, АААА-А17-117040610310-6, 0082-2014-0008, and АААА-А17-1170403100008-5; Russian Academic Project 5-100; and the Russian Foundation for Basic Research, project 18-04-00059a.

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Correspondence to A. F. Vanin.

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Translated by Victor Gulevich

Abbreviations: M-DNIC, mononuclear dinitrosyl iron complex; EPR, electron paramagnetic resonance; B-DNIC, binuclear dinitrosyl iron complex; DNIC–GSH, dinitrosyl iron complex with glutathione; GS–NO, S-nitrosoglutathione; NAC, N-acetyl-L-cysteine; S-NAC, S-nitroso-N-acetyl-L-cysteine; DNIC–NAC, dinitrosyl iron complex with N-acetyl-L-cysteine; EDTA, ethylene diamine tetraacetate; MNIC, mononitrosyl iron complex.

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Vanin, A.F. The Free-Radical Nature of Nitric Oxide Molecules as a Determinant of their Conversion to Nitrosonium Cations in Living Systems. BIOPHYSICS 65, 353–367 (2020). https://doi.org/10.1134/S0006350920030239

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