Free radical nitric oxide production

As reviewed in Chapter 3 of this book, nitric oxide is the product of the enzymatic oxidation of one of the guanidino nitrogen groups of L-arginine to the free radical nitric oxide and L-citrulline (Marietta etal., 1988). At present there appears to be at least three distinct isoforms of nitric oxide synthase that are primarily differentiated at the level of gene expression (Schmidt, 1992 Nathan,... 

As mentioned earlier, extensive literature is dedicated to the study of functions of NO synthases under physiological and pathophysiological conditions. Much attention has been drawn to the capacity of these enzymes to generate free radicals. The mechanism of nitric oxide production by NO synthases was widely discussed and are presented in Figure 22.3 [147]. 

An important side reaction in all free-radical nitrations is production, of unstable alkyl nitrites (cq. 7). They decompose to form nitric oxide and alkoxy radicals (eq. 8) which form oxygenated compounds and lower molecular weight alkyl radicals which can form lower molecular weight nitroparaffins by reactions 4 or 6 The oxygenated hydrocarbons often react further to produce carbon oxides and water. 

Huang, A., Li, C., Kao, R.L., and Stone, W.L., 1999a, Lipid hydroperoxides inhibit nitric oxide production in RAW264.7 macrophages, Free Radic. Biol. Med. 26 526-537. 

Pu, Y., McCormick, C.C., Roneker, C., and Lei, X.G. (2001). Lipopolysaccharide and interferon-gamma-induced nitric oxide production and protein oxidation in mouse peritoneal macrophages are affected by glutathione peroxidase-1 gene knockout. Free Radic Biol Med 31, 450-9. 

EGCG possesses beneficial effects in cardiovascular diseases in which inflammation and oxidative stress are the primary causes of concern. EGCG has been shown to inhibit DNA damage, LDL oxidation, and nitric oxide production. It has also been shown to scavenge free radicals, decrease the production of inflammatory mediators (such as cytokines and eicosanoids), and modulate inflammatory genes (such as NE-kB and... 

The H + NO2 OH + NO reaction provides an excellent example of the use of laser fluorescence detection for the elucidation of the dynamics of a chemical reaction. This reaction is a protot5q)e example of a radical-radical reaction in that the reagents and products are all open-shell free radical species. Both the hydroxyl and nitric oxide products can be conveniently detected by electronic excitation in the UV at wavelengths near 226 and 308 nm, respectively. Atlases of rotational line positions for the lowest electronic band systems of these... 

Peri, L., Pietraforte, D., Scorza, G., NapoUtano, A., Fogliano, V Minetti, M. (2005). Apples increase nitric oxide production by human saliva at the acidic pH of the stomach a new biological function for polyphenols with a catechol group Free Radical Biology Medicine, 39,668-681. 

Not all oxidants formed biolc cally have the potential to promote lipid peroxidation. The free radicals superoxide and nitric oxide [or endothelium-derived relaxing aor (EDRF)] are known to be formed in ww but are not able to initiate the peroxidation of lipids (Moncada et tU., 1991). The protonated form of the superoxide radical, the hydroperoxy radical, is capable of initiating lipid peroxidation but its low pili of 4.5 effectively precludes a major contribution under most physiological conditions, although this has been suggested (Aikens and Dix, 1991). Interestingly, the reaction product between nitric oxide and superoxide forms the powerful oxidant peroxynitrite (Equation 2.6) at a rate that is essentially difiiision controlled (Beckman eta/., 1990 Huie and Padmaja, 1993). 

Free Radical Production by Nitric Oxide Synthases... 

Simultaneous generation of nitric oxide and superoxide by NO synthases results in the formation of peroxynitrite. As the reaction between these free radicals proceeds with a diffusion-controlled rate (Chapter 21), it is surprising that it is possible to detect experimentally both superoxide and NO during NO synthase catalysis. However, Pou et al. [147] pointed out that the reason is the fact that superoxide and nitric oxide are generated consecutively at the same heme iron site. Therefore, after superoxide production NO synthase must cycle twice before NO production. Correspondingly, there is enough time for superoxide to diffuse from the enzyme and react with other biomolecules. 

In addition to nitric oxide, superoxide, and peroxynitrite, NO synthases are able to generate secondary free radicals because similar to cytochrome P-450 reductase, the reductase domain can transfer an electron from the heme to a xenobiotic. Thus it has been found [158,159] that neuronal NO synthase NOS I catalyzed the formation of CH3CH(OH) radical from ethanol. It was suggested that the perferryl complex of NOS I is responsible for the formation of such secondary radicals. Miller [160] also demonstrated that 1,3-dinitrobenzene mediated the formation of superoxide by nNOS. It was proposed that the enhancement of superoxide production in the presence of 1,3-dinitrobenzene converted nNOS into peroxynitrite-produced synthase and may be a mechanism of neurotoxicity of certain nitro compounds. 

---