The alpha-amino group of L-arginine mediates its antioxidant effect.

Antioxidant effects may constitute part of the possible antiatherogenic effects of the amino acid L-arginine. These antioxidant properties were further characterized in a model of lipoprotein oxidation. Oxidation of lipoproteins in unfractionated human serum was continuously monitored by a fluorescent probe. The antioxidant effects of L-arginine, N-alpha-acetyl-arginine and vitamin E in combination with L-arginine were measured after initiation of free radical generation with either copper or 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH). The half-time of the fast propagation rate for copper-induced lipoprotein oxidation increased after incubation with L-arginine in a dose-dependent manner (P < 0.01). N-alpha-acetyl-arginine did not show such effects. Vitamin E and L-arginine show different effects on copper-induced oxidation, the former increasing only lag-time, the latter increasing only propagation rate, and do not have reciprocal effects. In contrast to copper-induced oxidation, L-arginine increased the lag-time of AAPH-induced lipoprotein oxidation (P < 0.01), with no effect on the propagation rate at physiological concentrations. Again, N-alpha-acetyl-arginine did not show any antioxidant effects. Our experiments provide further evidence that mechanisms other than serving as a substrate for the NO-synthase could be involved in the antiatherosclerotic effect of L-arginine. In addition, our experiments clearly show, that the antioxidant effect of L-arginine is due to a chemical moiety different from that serving as the substrate for NO biosynthesis.