RT Journal Article
T1 An Insight into the Regiospecificity of Linoleic Acid Peroxidation Catalyzed by Mammalian 15-Lipoxygenases
A1 Suardíaz Delrío, Reynier
A1 Masgrau, Laura
A1 Lluch, José
A1 González-Lafont, Àngels
AB 15-Lipoxygenases (15-LOs) catalyze the peroxidation reaction of linoleic acid (LA) in mammals producing almost exclusively 13-(S)-hydroperoxyoctadecadienoic acid (13-(S)-HPODE). Although several hypotheses have been formulated, the molecular basis of such enzymatic regiospecificity is unclear. We have here combined quantum mechanics/molecular mechanics (QM/MM) calculations with molecular dynamics simulations to analyze the peroxidation mechanism using a complete rabbit 15-LO-1/LA solvated model. C9 and C13 being equivalent for planarity and spin density, the QM/MM potential energy profiles of the O2 addition to those two atoms were calculated. The difference in the potential energy barrier heights is clear enough to justify that O2 selectively attacks C13 giving 13-(S)-HPODE. Oxygenation at C9 is hindered by two steric-shielding residues (Leu597 and Gln548). The calculated free energy profile at 300 K for the O2 addition to C13 confirms that the peroxidation on C13 is a reversible viable process in agreement with experiments. Thus, the subsequent reduction of the peroxyl radical to give the final hydroperoxidated product is expected to give the irreversibility character to the overall process.
PB American Chemical Society
SN 1520-6106
YR 2013
FD 2013
LK https://hdl.handle.net/20.500.14352/92495
UL https://hdl.handle.net/20.500.14352/92495
LA eng
NO Suardíaz, Reynier, et al. «An Insight into the Regiospecificity of Linoleic Acid Peroxidation Catalyzed by Mammalian 15-Lipoxygenases». The Journal of Physical Chemistry B, vol. 117, n.o 14, abril de 2013, pp. 3747-54.  https://doi.org/10.1021/jp312747q.
NO Ministerio de Economía y Competitividad (España)
NO Generalitat deCatalunya
NO Alianza 4U
DS Docta Complutense
RD 6 abr 2025