Endogenous generation of nitro-fatty acid hybrids having dual nitrate ester (RONO₂) and nitroalkene (RNO₂) substituents.

ABSTRACT: Organic nitrate esters, long-recognized therapies for cardiovascular disorders, have not been detected biologically. We characterize in rat stomach unsaturated fatty acid nitration reactions that proceed by generation of nitro-nitrate intermediates (NO₂-ONO₂-FA) via oxygen and nitrite dependent reactions. NO₂-ONO₂-lipids represent ∼70% of all nitrated lipids in the stomach and they decay in vitro at neutral or basic pH by the loss of the nitrate ester group (-ONO₂) from the carbon backbone upon deprotonation of the α-carbon (pKa ∼7), yielding nitrate, nitrite, nitrosative species, and an electrophilic fatty acid nitroalkene product (NO₂-FA). Of note, NO₂-FA are anti-inflammatory and tissue-protective signaling med

SUBMITTER: Fazzari M 

PROVIDER: S-EPMC8049994 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature