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Publication : ABHD4 regulates multiple classes of N-acyl phospholipids in the mammalian central nervous system.

First Author  Lee HC Year  2015
Journal  Biochemistry Volume  54
Issue  15 Pages  2539-49
PubMed ID  25853435 Mgi Jnum  J:276423
Mgi Id  MGI:6316590 Doi  10.1021/acs.biochem.5b00207
Citation  Lee HC, et al. (2015) ABHD4 regulates multiple classes of N-acyl phospholipids in the mammalian central nervous system. Biochemistry 54(15):2539-49
abstractText  N-Acyl phospholipids are atypical components of cell membranes that bear three acyl chains and serve as potential biosynthetic precursors for lipid mediators such as endocannabinoids. Biochemical studies have implicated ABHD4 as a brain N-acyl phosphatidylethanolamine (NAPE) lipase, but in vivo evidence for this functional assignment is lacking. Here, we describe ABHD4(-/-) mice and their characterization using untargeted lipidomics to discover that ABHD4 regulates multiple classes of brain N-acyl phospholipids. In addition to showing reductions in brain glycerophospho-NAEs (GP-NAEs) and plasmalogen-based lyso-NAPEs (lyso-pNAPEs), ABHD4(-/-) mice exhibited decreases in a distinct set of brain lipids that were structurally characterized as N-acyl lysophosphatidylserines (lyso-NAPSs). Biochemical assays confirmed that NAPS lipids are direct substrates of ABHD4. These findings, taken together, designate ABHD4 as a principal regulator of N-acyl phospholipid metabolism in the mammalian nervous system.
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