Recent advances in DHA-containing phospholipids (PL-DHA): Sources, position-specific effects, metabolic pathways, and biological activities.

Docosahexaenoic acid-containing phospholipid (PL-DHA) exhibits superior bioavailability compared to conventional DHA formulations. Derived primarily from Antarctic krill or enzymatic synthesis, PL-DHA's molecular architecture-specifically its position-dependent distribution within the glycerol backbone and polar headgroup variations-critically influences membrane dynamics. Sn-1 position DHA generates "U-shaped" configurations affecting membrane fluidity, while sn-2 position maintains "hairpin" conformations optimal for enzymatic recognition. These structural characteristics enable specialized transport mechanisms, including Mfsd2a-mediated blood-brain barrier penetration. PL-DHA undergoes distinct tissue-specific metabolism, particularly in neural and hepatic tissues, modulating membrane properties and signal transduction. Its biological activities encompass anti-inflammatory, neuroprotective, and metabolic regulatory functions through both direct membrane effects and bioactive metabolite generation. This structure-function relationship provides crucial insights for developing targeted therapeutic applications in neurological and metabolic disorders.