N-Acylphosphatidylethanolamines are also an important intermediaries in the biosynthesis of endocannabinoids.
NAPEs are formed from phosphatidylethanolamines, a group of cell membrane phospholipids characteristic of nervous tissue. After being cleaved by phospholipases, NAPEs can be transformed into N-acylethanolamines, including the endocannabinoid anandamide.[2][3] While NAPE-PLD is the enzyme responsible for catalyzing said release of N-acylethanolamine (NAE) from N-acyl-phosphatidylethanolamine (NAPE), this specific subtype of phospholipase D is not responsible for the formation of the anandamide.[4]
The crystal structure of human N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) reveals how this membrane enzyme generates anandamide and other bioactive lipid amides from membrane NAPEs.[5] A hydrophobic cavity in NAPE-PLD provides an entryway for the substrate NAPE into the active site, where a binuclear zinc center orchestrates its hydrolysis. Unexpectedly, the structure unveils bile acids bind the membrane enzyme, enhancing dimer assembly and enabling catalysis. These findings suggest NAPE-PLD might orchestrate a direct crosstalk between bile acids and lipid amide signals.[5]
