The specificity of endogenous fatty acid nitration: only conjugated substrates support the in vivo formation of nitro-fatty acids

Through multiple pathways, nitrogen dioxide (•NO₂) is the main species involved in endogenous nitration reactions. Early studies in the field primarily explored tyrosine nitration, a dominant reaction in the field. It was later shown that lipids are also nitration targets and generate an array of reaction products. Conjugated fatty acids are the preferential substrates of lipid nitration in vivo, generating electrophilic nitro-fatty acids (NO₂–FAs), which serve as pleiotropic signaling modulators. In contrast, exposure of bisallylic fatty acids, including linoleic, linolenic and arachidonic acid, to •NO₂ does not lead, under biological conditions, to the formation of nitrated species. This review focuses on the reaction mechanisms and products of lipid nitration and substrate specificity, focusing on the differential reactivity of conjugated dienes and bisallylic alkenes.