Membrane "lens" effect: focusing the formation of reactive nitrogen oxides from the *NO/O2 reaction.

It was previously observed that lipid membranes accelerate *NO disappearance (Liu et al. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 2175), and here, we demonstrate that this translates into increased rates of *NO2 production and nitrosative chemistry. Not only the phospholipid membranes but also the atherosclerosis-related low-density lipoprotein (LDL) were able to accelerate the formation of *NO2, studied by stopped-flow spectrophotometry using ABTS as a probe. In addition, membranes, LDL, and Triton X-100 micelles significantly accelerated S-nitrosation of glutathione and captopril. It is shown here that autoxidation of *NO occurs 30 times more rapidly within the hydrophobic interior of these particles than in an equal volume of water, approximately 1 order of magnitude less than previous reports. This acceleration can be explained by the approximately 3 times higher solubility of *NO and O2 into these hydrophobic phases relative to water, which results in a higher local concentration of reactants ("lens effect") and, therefore, a higher rate of reaction. It is predicted that 50% of the oxidizing and nitrosating species derived from *NO autoxidation in cells will be formed in the small volume comprising cellular membranes (3% of the total); thus, biomolecules near the membranes will be exposed to fluxes of reactive nitrogen species 30-fold higher than their cytosolic counterparts.