N-acetylphosphatidylethanolamine-hydrolysing phospholipase D (NAPE-PLD) is the enzyme responsible of the biosynthesis of the endocannabinoid Anandamide.

Chemical Name: 
N-acetylphosphatidylethanolamine-hydrolysing phospholipase D
Wikipedia entry: 
Literature Discussion: 

NAPE-PDL is responsible for the biosynthesis of Anandamide (Liu et al., 2008; Okamoto, Tsuboi, & Ueda, 2009; Okamoto, Wang, Morishita, & Ueda, 2007; Ueda, Okamoto, & Morishita, 2005)

Deletion of NAPE-PLD influences a large number of lipids in different species and different parts of the brain (Leishman, Mackie, Luquet, & Bradshaw, 2016)

NAPE-PLD is located in the neuronal axons and its involved in the modulation of neuronal plasticity and retrograde signaling (Egertová, Simon, Cravatt, & Elphick, 2008; Nyilas et al., 2008)

NAPL-PDS expression is also downregulated in human glioma (Wu et al., 2012)

Alcohol use downregulates the expression of NAPE-PLD in microglia (Correa, De Laurentiis, & Franchi, 2016)

Multiple Sclerosis changes the expression of NAPL-PDS (Zhang, Hilton, Hanemann, & Zajicek, 2011)

NAPE-PLD expression is downregulated after proinflammatory stimuli, suggesting its role in inflammation (Zhu et al., 2011)

NAPE-PLD are co-expressed with nociceptive markers in primary sensory neurons (Sousa-Valente et al., 2017)

NAPL-PDS is upregulated in celiac disease (Battista et al., 2012)


Battista, N., Di Sabatino, A., Di Tommaso, M., Biancheri, P., Rapino, C., Vidali, F., … Maccarrone, M. (2012). Abnormal Anandamide metabolism in celiac disease. The Journal of Nutritional Biochemistry, 23(10), 1245-1248. https://doi.org/10.1016/j.jnutbio.2011.06.017

Correa, F., De Laurentiis, A., & Franchi, A. M. (2016). Ethanol downregulates N-acyl phosphatidylethanolamine-phospholipase D expression in BV2 microglial cells via epigenetic mechanisms. European Journal of Pharmacology, 786, 224-233. https://doi.org/10.1016/j.ejphar.2016.06.004

Egertová, M., Simon, G. M., Cravatt, B. F., & Elphick, M. R. (2008). Localization of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) expression in mouse brain: A new perspective on N-acylethanolamines as neural signaling molecules. The Journal of Comparative Neurology, 506(4), 604-615. https://doi.org/10.1002/cne.21568

Leishman, E., Mackie, K., Luquet, S., & Bradshaw, H. B. (2016). Lipidomics profile of a NAPE-PLD KO mouse provides evidence of a broader role of this enzyme in lipid metabolism in the brain. Biochimica Et Biophysica Acta, 1861(6), 491-500. https://doi.org/10.1016/j.bbalip.2016.03.003

Liu, J., Wang, L., Harvey-White, J., Huang, B. X., Kim, H.-Y., Luquet, S., … Kunos, G. (2008). Multiple pathways involved in the biosynthesis of Anandamide. Neuropharmacology, 54(1), 1-7. https://doi.org/10.1016/j.neuropharm.2007.05.020

Nyilas, R., Dudok, B., Urbán, G. M., Mackie, K., Watanabe, M., Cravatt, B. F., … Katona, I. (2008). Enzymatic machinery for endocannabinoid biosynthesis associated with calcium stores in glutamatergic axon terminals. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 28(5), 1058-1063. https://doi.org/10.1523/JNEUROSCI.5102-07.2008

Okamoto, Y., Tsuboi, K., & Ueda, N. (2009). Enzymatic formation of Anandamide. Vitamins and Hormones, 81, 1-24. https://doi.org/10.1016/S0083-6729(09)81001-7

Okamoto, Y., Wang, J., Morishita, J., & Ueda, N. (2007). Biosynthetic pathways of the endocannabinoid Anandamide. Chemistry & Biodiversity, 4(8), 1842-1857. https://doi.org/10.1002/cbdv.200790155

Sousa-Valente, J., Varga, A., Torres-Perez, J. V., Jenes, A., Wahba, J., Mackie, K., … Nagy, I. (2017). Inflammation of peripheral tissues and injury to peripheral nerves induce differing effects in the expression of the calcium-sensitive N-arachydonoylethanolamine-synthesizing enzyme and related molecules in rat primary sensory neurons. The Journal of Comparative Neurology, 525(8), 1778-1796. https://doi.org/10.1002/cne.24154

Ueda, N., Okamoto, Y., & Morishita, J. (2005). N-acylphosphatidylethanolamine-hydrolyzing phospholipase D: a novel enzyme of the beta-lactamase fold family releasing Anandamide and other N-acylethanolamines. Life Sciences, 77(14), 1750-1758. https://doi.org/10.1016/j.lfs.2005.05.018

Wu, X., Han, L., Zhang, X., Li, L., Jiang, C., Qiu, Y., … Fu, J. (2012). Alteration of endocannabinoid system in human gliomas. Journal of Neurochemistry, 120(5), 842-849. https://doi.org/10.1111/j.1471-4159.2011.07625.x

Zhang, H., Hilton, D. A., Hanemann, C. O., & Zajicek, J. (2011). cannabinoid receptor and N-acyl phosphatidylethanolamine phospholipase D--evidence for altered expression in Multiple Sclerosis. Brain Pathology (Zurich, Switzerland), 21(5), 544-557. https://doi.org/10.1111/j.1750-3639.2011.00477.x

Zhu, C., Solorzano, C., Sahar, S., Realini, N., Fung, E., Sassone-Corsi, P., & Piomelli, D. (2011). Proinflammatory stimuli control N-acylphosphatidylethanolamine-specific phospholipase D expression in macrophages. Molecular Pharmacology, 79(4), 786-792. https://doi.org/10.1124/mol.110.07020