Formation of nitrosothiols from gaseous nitric oxide at pH 7.4

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Abstract
Nitric oxide (NO) is generated in biological systems and plays important roles as a regulatory molecule. Its ability to bind to haem iron is well known. Moreover, it may lose an electron, forming the nitrosonium ion, involved in the synthesis of S‐nitrosothiols (SNOs). It has been suggested that S‐nitrosohaemoglobin (−SNO Hb) and low molecular weight SNOs may act as reservoirs of NO. SNOs are formed in vitro, at strongly acidic pH values; however, the mechanism of their formation at neutral pH values is still debated. In this paper we report the anaerobic formation of SNOs (both high‐ and low‐molecular weight) from low concentrations of NO at pH 7.4, provided Hb is also present. We propose a reaction mechanism entailing the participation of Fehaem in the formation of NO+ and the transfer of NO+ either to Cysβ93 of Hb or to glutathione; we show that this reaction also occurs in human RBCs. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:135–139, 2002. DOI 10.1002/jbt.10028