Figure 6. LDL-DHA Metabolism.
Following intracellular uptake by the LDL receptor, DHA is liberated from the LDL nanoparticle. Unesterified DHA can be: activated by Long-chain-fatty-acid— CoA ligase (ACSL) for esterification into sn2 position in membrane phospholipids; metabolized sequentially via lipoxygenase enzyme system to resolvins; or alternatively, undergo free radical mediated lipid peroxidation to aldehyde end products. DHA delivered to the brain by the LDL nanoparticles preferentially undergoes oxidation via the lipoxygenase pathway rather than free radical degradation. PLA2, phospholipase A2; 15-LOX, 15-lipoxygenase; 5-LOX, 5-lipoxygenase; TBARS, thiobartuic reactive substances.