P-4 - Nitration of fatty acids, and the release of nitric oxide from nitrated fatty acids

Abstract

Nitrated fatty acids (NFAs) exhibit a variety of important biological functions, including nitric oxide (NO) donor and cell signaling molecule. We investigated the mechanisms of the nitration of fatty acids, and the release of NO from NFAs. NFAs are formed more effectively by the addition of nitrogen dioxide via the N-end, followed by hydrogen abstraction or by addition of the second nitrogen dioxide. The latter reaction results in vicinal nitronitrite ester form of FA, which isomerizes into vicinal nitrohydroxy FA via hydronium ion catalysis. The nitrohydroxy FAs exist in equilibria with NFAs. Nitration of conjugated linoleic acid (cLA) was demonstrated to be significantly more efficient than that of LA. In non-aqueous environment, release of NO via nitrite ester (ONO-FA) was shown to be facilitated by nitrogen dioxide. Furthermore, the release of NO from NcLA is the most favorable in the nitrite ester mechanism. In aqueous environment, modified Nef mechanism was shown to be feasible. In contrast, the release of NO from 10- and 12-NLA involve larger reaction barrier and are more endergonic than 9- and 13-NLA.