Enzymes in brain phospholipid docosahexaenoic acid accretion: A PL-ethora of potential PL-ayers

Neural tissue is highly enriched in docosahexaenoic acid (DHA) that is primarily found in the sn-2 position of ethanolamine-containing phospholipids and plasmalogens. Current knowledge on the activity of enzymes in brain phospholipid synthesis does not fully explain this composition and stereospecificity. It is likely that a host of enzyme-mediated processes play roles in brain DHA accumulation to develop this unique enrichment and phospholipid profile. This review examines current knowledge on the spectrum of enzymes that may be involved in brain DHA uptake and utilization in the synthesis and remodeling of phospholipids. It also highlights gaps in that knowledge, including missing information on the activity of known brain enzymes towards DHA as a substrate, and missing identities of brain enzymes that catalyze orphan reactions utilizing DHA for phospholipid formation.