Nitric oxide , chemical biology

F. Bedioui, S. Trevin, and J. Devynck, Chemically modified microelectrodes designed for the electrochemical determination of nitric oxide in biological systems. Electroanalysis 8, 1085-1091 (1996). 

Although much of the biological literature focuses on nitrosating reactions of nitric oxide, chemically nitric oxide is a moderate one-electron oxidant, making formation of nitroxyl anion feasible under physiological conditions. The reduction potential to reduce nitric oxide to nitroxyl anion is +0.39 V, whereas it requires +1.2 V to oxidize nitric oxide to nitrosonium ion. Nitrosating reactions of nitric oxide are often mediated by conversion of nitric oxide to another nitrogen oxide species or by direct reaction with transition metals (Wade and Castro, 1990). 

Morpholinosydnonimine-N-ethylcarbamide (molsidomine) is enzymatically transformed to 3-morpholinosydnonimine (SIN-1), which hydrolyses in a pH-dependent manner to form open-ring chemical compounds such as N-morpholino-N-nitrosoaminoacetonitrile (SIN-IA), which then decomposes to form nitric oxide and biologically inactive metabolites like SIN-IC (Noack and Fee-LiscH 1989). In an aqueous solution 500 jiM SIN-1 were degraded to SIN-IA with a half-time of... 

Hu, C. et al., Black rice (Oryza sativa L. indica) pigmented fraction suppresses both reactive oxygen species and nitric oxide in chemical and biological model systems, J. Agric. Food Chem., 51, 5271, 2003. 

The discovery of nitric oxide in living organisms was a great event in the development of free radical studies in biology. NO is a gaseous neutral free radical with relatively long lifetime and at the same time is an active species capable of participating in many chemical reactions. 

Despite intense study of the chemical reactivity of the inorganic NO donor SNP with a number of electrophiles and nucleophiles (in particular thiols), the mechanism of NO release from this drug also remains incompletely understood. In biological systems, both enzymatic and non-enzymatic pathways appear to be involved [28]. Nitric oxide release is thought to be preceded by a one-electron reduction step followed by release of cyanide, and an inner-sphere charge transfer reaction between the ni-trosonium ion (NO+) and the ferrous iron (Fe2+). Upon addition of SNP to tissues, formation of iron nitrosyl complexes, which are in equilibrium with S-nitrosothiols, has been observed. A membrane-bound enzyme may be involved in the generation of NO from SNP in vascular tissue [35], but the exact nature of this reducing activity is unknown. 

The importance of the dihydro and tetrahydro oxidation states of pterins in biology has stimulated interest in the study of the chemical properties of these compounds, especially with respect to electron-transfer and radical reactions. It has become apparent, perhaps unsurprisingly, that the stability and reactivity of these oxidation states are very sensitive to substituent effects and the much greater stability of the fully conjugated pteridines is most evident. The oxidation of tetrahydropterins and the reduction of dihydropterins have become especially important in the chemistry of nitric oxide production in nature and in oxidative stress but the accumulation of relevant facts has not led so far to a detailed understanding of the chemical property relationships. Relevant information is summarized in the following section. 

Ritter, J. A., D. H. Stedman, and T. J. Kelly, Ground-Level Measurements of Nitric Oxide, Nitrogen Dioxide and Ozone in Rural Air, in Nitrogenous Air Pollutants Chemical and Biological Implications, pp. 325-343, Ann Arbor Science Publishers, Ann Arbor, MI., (1979). 

Most messenger molecules encode information within their shape, which is recognized by a specific receptor. Nitric oxide is the smallest of biological messenger molecules, with the possible exception of carbon monoxide. Because of its chemical simplicity, nitric oxide must convey information by its concentration, which is interpretable by the spatial proximity of the source and target cells and the short duration of nitric oxide. Thus, the short half-life and limited diffusion distance of nitric oxide confers specificity, allowing the target tissue to derive information based solely on nitric oxide concentration. 

Clearly, the short half-life of nitric oxide is an important determinant for its biological function, but the chemical basis for this short half-life is still unknown. It cannot be due to the most commonly accepted mechanism reaction with oxygen to form nitrogen dioxide. 

The chemistry of the nitrogen oxides dates back to the days of the Reverend Joseph Priestley, who used the reaction of nitric oxide to measure the concentration of oxygen in air. As a consequence, many of the recommended lUPAC names for nitrogen species have common names. As a general rule, common names are used when they have been widely utilized in the biological literature and lUPAC names for less well-known chemical species. Table 3 should help facilitate translation among the different names. 

Fukuto, J. M., Wallace, G. C., Hszieh, R., and Chaudhuri, G. (1992). Chemical oxidation of N hydroxyguanidine compounds. Release of nitric oxide, nitroxyl and possible relationship to the mechanism of biological nitric oxide generation. Biochem. Pharmacol. 43, 607-613. 

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