The Free-Radical Nature of Nitric Oxide Molecules as a Determinant of their Conversion to Nitrosonium Cations in Living
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CULAR BIOPHYSICS
The Free-Radical Nature of Nitric Oxide Molecules as a Determinant of Their Conversion to Nitrosonium Cations in Living Systems A. F. Vanina, b, * a
Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, 119334 Russia of Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, 119991 Russia *e-mail: [email protected]
bInstitute
Received March 13, 2020; revised March 13, 2020; accepted March 16, 2020
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-acetylL-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. Keywords: dinitrosyl iron complexes, nitric oxide, S-nitrosothiols, electron paramagnetic resonance DOI: 10.1134/S0006350920030239
All living organisms, that is, humans, animals, plants, and bacteria, constantly produce a simple chemical compound, nitric oxide (NO; also known as nitrogen oxide or nitrogen monoxide) by an enzymatic pathway. This substance is one of the universal regulators of various physiological and biochemical processes [1]. Its biologic action is not mediated by cell surface receptors, as nitric oxide readily permeates through cell membranes. By binding to the heme groups of various heme-containing enzymes, such as guanylate cyclase, it activates or inhibits these enzymes.
cation (NO+) is no less important. Its binding to thiol groups of proteins forms corresponding S-nitrosothiols (RSNO), which alter th
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