Peroxyl radical, reaction with nitric oxide

Mouse peritoneal macrophages that have been activated to produce nitric oxide by 7-interferon and lipopolysac-charide were shown to oxidize LDL less readily than unactivated macrophages. Inhibition of nitric oxide synthesis in the same model was shown to enhance LDL oxidation (Jessup etal., 1992 Yates a al., 1992). It has recently been demonstrated that nitric oxide is able to inhibit lipid peroxidation directly within LDL (Ho etal., 1993c). Nitric oxide probably reacts with the propagating peroxyl radicals thus terminating the chain of lipid peroxidation. The rate constant for the reaction between nitric oxide and peroxyl radicals has recently been determined to be 1-3 X10 M" s (Padmaja and Huie, 1993). This... 

Padmaja, S. and Huie, RE. (1993). The reaction of nitric oxide with organic peroxyl radicals. Biochem. Biophys. Res. Commun. 195, 539-544. 

Padmaja S, Huie RE. (1993) Reaction of nitric oxide with peroxyl radicals. Biochem Biophys Res Comm 195 539. 

R8 is the simplest of a large suite of peroxyl radical combination reactions, generalized as R02 + H02 and R02 + R02 that generate poorly characterized radical and non-radical reaction products. Such reactions are of greatest significance in air with low nitric oxide concentration where the R02 species can reach elevated concentrations (95). The dependence of [H02 ] upon the tropospheric NO concentration is discussed below. 

As mentioned earlier, when NO concentration exceeds that of superoxide, nitric oxide mostly exhibits an inhibitory effect on lipid peroxidation, reacting with lipid peroxyl radicals. These reactions are now well studied [42-44]. The simplest suggestion could be the participation of NO in termination reaction with peroxyl radicals. However, it was found that NO reacts with at least two radicals during inhibition of lipid peroxidation [50]. On these grounds it was proposed that LOONO, a product of the NO recombination with peroxyl radical LOO is rapidly decomposed to LO and N02 and the second NO reacts with LO to form nitroso ester of fatty acid (Reaction (7), Figure 25.1). Alkoxyl radical LO may be transformed into a nitro epoxy compound after rearrangement (Reaction (8)). In addition, LOONO may be hydrolyzed to form fatty acid hydroperoxide (Reaction (6)). Various nitrated lipids can also be formed in the reactions of peroxynitrite and other NO metabolites. 

As mentioned earlier, ascorbate and ubihydroquinone regenerate a-tocopherol contained in a LDL particle and by this may enhance its antioxidant activity. Stocker and his coworkers [123] suggest that this role of ubihydroquinone is especially important. However, it is questionable because ubihydroquinone content in LDL is very small and only 50% to 60% of LDL particles contain a molecule of ubihydroquinone. Moreover, there is another apparently much more effective co-antioxidant of a-tocopherol in LDL particles, namely, nitric oxide [125], It has been already mentioned that nitric oxide exhibits both antioxidant and prooxidant effects depending on the 02 /NO ratio [42]. It is important that NO concentrates up to 25-fold in lipid membranes and LDL compartments due to the high lipid partition coefficient, charge neutrality, and small molecular radius [126,127]. Because of this, the value of 02 /N0 ratio should be very small, and the antioxidant effect of NO must exceed the prooxidant effect of peroxynitrite. As the rate constants for the recombination reaction of NO with peroxyl radicals are close to diffusion limit (about 109 1 mol 1 s 1 [125]), NO will inhibit both Reactions (7) and (8) and by that spare a-tocopherol in LDL oxidation. 

Peroxyl radicals are not only ones, which are able to react with ubihydroquinones. Poderoso et al. [245] showed that the short-chain ubihydroquinones Q0 and Q2 are oxidized by nitric oxide with the rate constants of 0.49 x 104 and 1.6x 1041 mol-1 s 1, respectively. The reaction apparently proceeded by one-electron transfer mechanism because the formation of intermediate semiquinone radicals has been registered. 

O DormeU, V. B., Chumley, P. H., Hogg, N., Bloodsworth, A., Darley-Usmar, V. M., and Freeman, B. A., 1997, Nitric oxide inhibition of Upid peroxidation kinetics of reaction with lipid peroxyl radicals and comparison with alpha-tocopherol, Biochemistry 36 15216-15223. 

Ruhho, H., Radi, R., Ansehni, D., Kirk, M., Bames, S., Butler, J., Fiserich, J. P., and Freeman, B. A., 2000, Nitric oxide reaction with hpid peroxyl radicals spares alpha-tocopherol during hpid peroxidation. Greater oxidant protection from the pair nitric oxide/alpha-tocopherol than alpha-tocopherol/ascorbate, J. Biol. Chem. 275 10812-10818. 

Rubbo H, Radi R, Anselmi D, Kirk M, Barnes S, Butler J, Eiserich JP, Freeman BA (2000) Nitric oxide reaction with lipid peroxyl radicals spares a-tocopherol during lipid peroxidation. Greater oxidant protection from the pair nitric oxide/a-tocopherol than a-to-copherol/ascorbate. J Biol Chem 275 10812-10818... 

Rubbo H, Radi R, Anselmi D (2000) Nitric oxide reaction with lipid peroxyl radicals spares a-tocopherol during lipid peroxidation. J Biol Chem 275 10812-10818... 

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