N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)

N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) is a membrane-associated enzyme that hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce bioactive N-acylethanolamines, including fatty acid ethanolamides such as anandamide, which are involved in endocannabinoid signaling. NAPE-PLD is encoded by the NAPEPLD gene and contains a binuclear zinc center in its active site, characteristic of a metallo beta-lactamase fold. The enzyme’s activity is critical for the biosynthesis of several lipid mediators that participate in diverse physiological processes, including neural function, inflammation control, energy homeostasis, thermogenesis, and communication between the gut, immune system, and adipose tissue. Research has linked dysregulation of this enzyme to metabolic diseases, inflammation, neuropsychiatric disorders, and substance abuse. Regulation of NAPE-PLD by endogenous molecules (such as bile acids) and exogenous inhibitors is an area of active research with therapeutic potential.

Other names

N-acylphosphatidylethanolamine-hydrolyzing phospholipase DN-acetylphosphatidylethanolamine-hydrolysing phospholipase DNAPE-hydrolyzing phospholipase DNAPEPNAPEPLD (gene symbol)Anandamide-generating phospholipase D

Inhibitors prevent hydrolysis of NAPE to NAEs, reducing levels of bioactive endocannabinoids and related lipids; this can impact inflammation, energy balance, and neuroprotection. Modulators (such as bile acids) enhance or regulate enzyme activity by stabilizing protein structure and dimerization, thus altering the production of lipid mediators.