Mechanisms of nitric oxide generation in living systems

• Published in: Nitric oxide Vol. 118; pp. 1 - 16
• Main Authors: Burov, Oleg N., Kletskii, Mikhail E., Kurbatov, Sergey V., Lisovin, Anton V., Fedik, Nikita S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2022
• Subjects: Arginine - chemistry; Arginine - metabolism; Endogenous sources of NO; Enzymatic pathway of NO formation; Exogenous sources of NO; Humans; Models, Chemical; Nitric Oxide - biosynthesis; Nitric Oxide Donors - chemistry; Nitric Oxide Donors - metabolism; Nitrogen(II) oxide; Quantum chemical calculations; S-Nitrosothiols - chemistry; S-Nitrosothiols - metabolism; Thiol-induced NO donation Mechanism; Enzymatic pathway of NO formation; Endogenous sources of NO; Quantum chemical calculations; Thiol-induced NO donation Mechanism; Exogenous sources of NO; Nitrogen(II) oxide
• ISSN: 1089-8603; 1089-8611; 1089-8611
• DOI: 10.1016/j.niox.2021.10.003

In modern chemical and biochemical studies, special attention is paid to molecular systems capable of generating nitric oxide (NO), which is one of the most important signalling molecules in the body and can trigger a whole cascade of reactions. Despite the importance of this molecule, the mechanisms of its formation in living organisms remain a subject of debate. This review combines the most important methods of releasing NO from endogenous and exogenous sources. The history of endogenous NO donors dates back more than 150 years, since the synthesis of nitroglycerin, which remains the standard vasodilator today, even though it is known that it and many other similar compounds lead to the development of a nitrate tolerance. Particular awareness is devoted to the mechanisms of NO formation without the participation of enzymes, since these methods are most important for creating exogenous sources of NO as drugs. The study of NO formation methods is centred on both the creation of new NO donors and understanding the mechanisms of tolerance to them. [Display omitted] •The most important source of NO is electro neutral, zwitterionic or protonated form of l-arginine.•l-arginine is converted to l-citrulline under the action of NO synthases with the release of NO.•Exogenous sources of NO can donate nitric oxide upon the action of thiols.•Nitrosothiols are responsible for intracellular deposition and transport of NO.•NO elimination can occur as a result of intramolecular decomposition, light or thermal exposure.