Polyunsaturated fatty acid bis-allylic position (PUFA bis-allylic position)

The bis-allylic position in polyunsaturated fatty acids is a chemically reactive site located between two double bonds in the fatty acid backbone. Hydrogens at these positions are particularly susceptible to abstraction by reactive oxygen species (ROS) or enzymes such as lipoxygenases, initiating lipid peroxidation chain reactions. These events are central to processes like ferroptosis, oxidative stress-induced cell death, and the production of lipid signaling molecules. Replacement of bis-allylic hydrogens with deuterium (D-PUFA) strengthens the bond, rendering these sites more resistant to ROS attack, and has been shown experimentally to protect cells and organisms against lipid peroxidation-driven diseases. However, the bis-allylic position is not a molecular target in the conventional sense (e.g., not a receptor, enzyme, or protein), but rather a vulnerable structural aspect of certain fatty acids critical in cell biology and disease pathogenesis.

Other names

bis-allylic position of PUFAbis-allylic hydrogen in polyunsaturated fatty acidsPUFA bis-allylic site

Deuteration at the bis-allylic position slows the rate of hydrogen abstraction and suppresses lipid peroxidation, conferring cellular protection from ferroptosis and oxidative stress