Nitric oxide biological targets

Chemistry of B12-Dependent Enzyme Reactions Metallo-Enzymes and Metallo-Proteins, Chemistry of Nitric Oxide, Biological Targets of NMR Overview of Applications in Chemical Biology NMR for Proteins... 

Fig. 2. Interplay among superoxide anion, nitric oxide, and eicosanoids in high oxidative stress. The biological function of nitric oxide in target cells is influenced by the cellular redox state. In increased oxidative stress, which results in an oxidizing environment, NO readily form free radicals, including the highly reactive peroxynitrite (OONO ). Peroxynitrite can influence eicosanoid synthesis by interfering with different enzyme systems of the arachidonic acid cascade. Increased free radicals may also catalyze nonenzymic peroxidation of membrane PUFA (e.g., arachidonic acid), resulting in increased production of isoprostanes that possess potent vasoconstrictor activity. PLA, phospholipase NO, nitric oxide NOS, nitric oxide synthase NADPH oxidase, vascular NAD(P)H oxidase 02 , superoxide anion PUFA, polyunsaturated fatty acids EPA, eicosapentaenoic acid DHA, docosahexaenoic acid COX, cyclooxygenase PGI2 synthase, prostacyclin synthase.

Ford, P.C., Bourassa, J., Miranda, K. et al. (1998) Photochemistry of metal nitrosyl complexes. Delivery of nitric oxide to biological targets, Coord. Chem. Rev., 171, 185. 

The NO/NO+ and NO/NO- self-exchange rates are quite slow (42). Therefore, the kinetics of nitric oxide electron transfer reactions are strongly affected by transition metal complexes, particularly by those that are labile and redox active which can serve to promote these reactions. Although iron is the most important metal target for nitric oxide in mammalian biology, other metal centers might also react with NO. For example, both cobalt (in the form of cobalamin) (43,44) and copper (in the form of different types of copper proteins) (45) have been identified as potential NO targets. In addition, a substantial fraction of the bacterial nitrite reductases (which catalyze reduction of NO2 to NO) are copper enzymes (46). The interactions of NO with such metal centers continue to be rich for further exploration. 

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. 

A primary intracellular target for the biological actions of nitric oxide ( NO) production is intracellular iron (Hibbs et al., 1990 Henry et al., 1993). In activated macrophages and their tumor cell targets, a characteristic pattern of metabolic dysfunction is observed as a result of -NO synthesis, which includes loss of nonheme iron-containing enzyme function, including aconitate hydratase, complexes I and II of the mitochondrial electron transfer chain (Hibbs et al., 1990) as well as the nonheme iron-containing enzyme ribonucleotide reductase (Lepoivre et al., 1991). 

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