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

Academic Article
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Overview

authors

  • Lee, H. C.
  • Simon, Gabriel
  • Cravatt, Benjamin

publication date

  • April 2015

journal

  • Biochemistry  Journal

abstract

  • 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.

subject areas

  • Animals
  • Brain
  • Brain Chemistry
  • Lysophospholipase
  • Mice
  • Mice, Knockout
  • Phosphatidylethanolamines
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Identity

PubMed Central ID

  • PMC4767004

International Standard Serial Number (ISSN)

  • 0006-2960

Digital Object Identifier (DOI)

  • 10.1021/acs.biochem.5b00207

PubMed ID

  • 25853435
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Additional Document Info

start page

  • 2539

end page

  • 2549

volume

  • 54

issue

  • 15

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