Nitric oxide inhibition of lipid peroxidation: Kinetics of reaction with lipid peroxyl radicals and comparison with α-tocopherol

Academic Article


  • The reaction between nitric oxide (·NO) and lipid peroxyl radicals (LOO·) has been proposed to account for the potent inhibitory properties of ·NO toward lipid peroxidation processes; however, the mechanisms of this reaction, including kinetic parameters and nature of termination products, have not been defined. Here, the reaction between linoleate peroxyl radicals and ·NO was examined using 2,2'-azobis(2-amidinopropane) hydrochloride- dependent oxidation of linoleate. Addition of ·NO (0.5-20 μM) to peroxidizing lipid led to cessation of oxygen uptake, which resumed at original rates when all ·NO had been consumed. At high ·NO concentrations (>3 μM), the time of inhibition (T(inh)) of chain propagation became increasingly dependent on oxygen concentration, due to the competing reaction of oxygen with ·NO. Kinetic analysis revealed that a simple radical-radical termination reaction (·NO:ROO· = 1:1) does not account for the inhibition of lipid oxidation by ·NO, and at least two molecules of ·NO are consumed per termination reaction. A mechanism is proposed whereby ·NO first reacts with LOO· (k = 2 x 109 M-1 s-1) to form LOONO. Following decomposition of LOONO to LO· and ·NO2, a second NO is consumed via reaction with LO·, with the composite rate constant for this reaction being k = 7 x 104 M-1 s-1. At equal concentrations, greater inhibition of oxidation was observed with ·NO than with α-tocopherol. Since ·NO reacts with LOO· at an almost diffusion-limited rate, steady state concentrations of 30 nM ·NO would effectively compete with endogenous α-tocopherol concentrations (about 20 μM) as a scavenger of LOO· in the lipid phase. This indicates that biological ·NO concentrations (up to 2 μM) will significantly influence peroxidation reactions in vivo.
  • Published In

  • Biochemistry  Journal
  • Digital Object Identifier (doi)

    Author List

  • O'Donnell VB; Chumley PH; Hogg N; Bloodsworth A; Darley-Usmar VM; Freeman BA
  • Start Page

  • 15216
  • End Page

  • 15223
  • Volume

  • 36
  • Issue

  • 49