Nitric oxide production reduction

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. 

Two further perspectives on the use of tetracychnes in rheumatoid arthritis have been pubhshed (14,15). In addition to an effect on matrix metalloproteinases, the authors focused on a potential antiarthritic action of tetracyclines by their effects in the interaction between the generation of nitric oxide, matrix metalloproteinase release, and chondrocyte apoptosis. Both minocychne and doxycycline inhibit the production of nitric oxide from human cartilage and murine macrophages (16) in concentrations that are achieved in vivo. The authors suggested that tetracyclines may have several potential chondroprotective effects direct inhibition of matrix metalloproteinase activity and, by inhibition of nitric oxide production, further reduction of matrix metalloproteinase activity, reversal of reduced matrix synthesis, and reduced chondrocyte apoptosis. 

All isoflavones [daidzein (27), genistein (28)] and isoflavanones (17, 86-93) did not stimulate nitric oxide production by mouse macrophage-like Raw 264.7 cells, but almost completely inhibited NO production by the lipopolysaccharide (LPS)-activated Raw 264.7 cells. ESR spectroscopy showed that secundifloran (88) and secundiflorol D (90), which showed the most inhibitory effect for NO production, efficiently scavenged the superoxide anion and NO radicals. From these results, it is suggested that the inhibition of macrophage NO production by these isoflavanones might, at least in part, be explained by their radical scavenging or reduction activity (Fig. 17) (Tables 3, 4) [16]. 

Kumagai Y, Neuronal nitric oxide synthase (nNOS) catalyzes one-electron reduction of 2,4,6-trinitrotoluene, resulting in decreased nitric oxide production and increased nNOS gene expression Implication for oxidative stress, Free Radio. Biol. Med., 37, 350, 2004. 

Weinberg, J. B., Granger, D. L., Pisetsky, D. S., Seldin, M. F., Misukonis, M. A., Mason, S. N., Pippin, A. M., Ruiz, P., Wood, E. R., and Gilkeson, G. S. (1994). The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease Increased nitric oxide production and nitric oxide synthase expression in MRL-/pr//pr mice, and reduction of spontaneous nephritis and arthritis by orally administered N -monomethyl-L-arginine. J. Exp. Med. 179, 651-660. 

Weinberg JB, Granger DL, Pisetsky DS et al. The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease Increased nitric oxide production and nitric oxide synthase expression in MRL-lpr/lpr mice, and reduction of spontaneous glomerulonephritis and arthritis by orally administered NG-monomethyl-L-arginine. J Exp Med 1994 179 651-60. 

BMR was able to support high-level nitric oxide production by the fused nNOS heme domain, suggesting efficient electron transfer between the domains [209]. However, the protein stability of this hybrid enzyme was reduced and the rate of nitric oxide production was approximately eightfold lower than measured for native nNOS [209]. In contrast, with the converse hybrid, the nNOS reductase domain was rather unproductive at supporting reduction of the P450 BM3 heme domain, likely due to an inappropriate large distance between the flavin and heme redox centers [209]. Active fusions between RhFRed and a plant P450 has been recently described [210],... 

In contrast, the late-gestation fetus can accommodate for a slowly developing hypoxia for several hours by a combination of increased oxygen extraction, increased oxygen-carrying capacity, behavioral-state alterations and redistribution of CVO (145). A reduction in metabolic rate under these conditions is likely to be influenced by an increased rate of nitric oxide production. In vitro studies of car-diomyocytes, vascular smooth muscle cells, and hepatocytes have shown that there are reversible reductions in metabolic rate in cells held at a PO2 of 40 mmHg or less for 2h or more (8,123,146). 

Nitric oxide and NjO are direct intermediates in the denitrification pathway, the reduction of NO3 to Nj. Reduction to Nj is often incomplete, so that both NjO and Nj are equally important end products of denitrification, the ratio of NjO/Nj production being determined by soil physical properties. For example, NjO is the main end-product in acid soils, whereas low redox potentials and high organic matter content favour the further reduction to Nitric... 

Nitric oxide is the simplest thermally stable odd-electron molecule known and, accordingly, its electronic structure and reaction chemistry have been very extensively studied. The compound is an intermediate in the production of nitric acid and is prepared industrially by the catalytic oxidation of ammonia (p. 466). On the laboratory scale it can be synthesized from aqueous solution by the mild reduction of acidified nitrites with iodide or ferrocyanide or by the disproportionation of nitrous acid in the presence of dilute sulfuric acid ... 

Nitroxides are iV, iV-disubsdnited nitric oxide radicals, the unpaired electron being delocalized between the nitrogen and oxygen The reduction of 2-methyl-2-nitropropane with sodium or electrochemically yields di-r-butyl nitroxide as the final product " Such nitroxide radicals are important for the snidy of a organic ferromagnet... 

A relationship between polyol pathway activity and reduction in endothelium-dependent relaxation in aorta from chronic STZ-diabetic rats has recently been reported (Cameron and Cotter, 1992). In agreement with several previous studies (Oyama et al., 1986 Kamata et al., 1989), endothelial-dependent relaxation was defective in the diabetic rats but the deficit was prevented by prior treatment with an AR inhibitor. The mechanism underlying the defect has been speculated to be due to decreased production of endothelium-derived relaxing factor (EDRF) or nitric oxide, NO (Hattori et al., 1991). It has been speculated that these vascular abnormalities may lead to diminished blood flow in susceptible tissues and contribute to the development of some diabetic complications. NO is synthesized from the amino-acid L-arginine by a calcium-dependent NO synthase, which requires NADPH as a cofactor. Competition for NADPH from the polyol pathway would take place during times of sustained hyperglycaemia and... 

Water soluble iron porphyrins [Fem(TPPS)(H20) ]3-330 and [Fem(TMPy)(H20)2]5+ 331 332 (TPPS = maso-tetrakis(/ -sulfonatophenyl)porphyrin, TMPyP = / /e.vo-tetrakis(7V-methyl-4-pyridi-nium)porphyrin331 or maso-tetrakis (A -methyl-2-pyridinium)porphyrin332 dications) act as effective electrocatalysts for the reduction of nitrite to ammonia in aqueous electrolytes (Equation (64) Ei/2= 0.103 V vs. SCE at pH 7), with NH2OH or N20 also appearing as products depending on the reaction conditions. Nitric oxide then ligates to the iron(III) porphyrin to form a nitrosyl complex [Fen(P)(NO+)] (P = porphyrin) as intermediate. 

However, aluminum forms an oxide layer on the surface, and it becomes passive to further action. Sulfur is oxidized to sulfuric acid, with the reduction product being nitric oxide. 

However, at high rates of nitric oxide flux, the formation of nitrated and oxidized products became insensitive to the presence of catalase or MPO inhibitors but increasingly inhibited by SOD, suggesting the participation of peroxynitrite. (It is interesting that Reaction (30) might be a one-electron reduction of hydrogen peroxide by nitrite ion. If such a process really takes... 

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