N-Acylphosphatidylethanolamines (NAPEs) arehormones released by thesmall intestine into thebloodstream when it processesfat. NAPEs travel to thehypothalamus in the brain and suppressappetite. This mechanism could be relevant for treatingobesity.[1]
N-Acylphosphatidylethanolamines are also an important intermediaries in the biosynthesis ofendocannabinoids.
NAPEs are formed fromphosphatidylethanolamines, a group of cell membranephospholipids characteristic of nervous tissue. After being cleaved byphospholipases, NAPEs can be transformed intoN-acylethanolamines, including the endocannabinoidanandamide.[2][3] WhileNAPE-PLD is the enzyme responsible for catalyzing said release of N-acylethanolamine (NAE) from N-acyl-phosphatidylethanolamine (NAPE), this specific subtype ofphospholipase D is not responsible for the formation of the anandamide.[4]
The crystal structure of humanN-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) reveals how this membrane enzyme generatesanandamide and other bioactive lipid amides from membrane NAPEs.[5] A hydrophobic cavity inNAPE-PLD provides an entryway for the substrate NAPE into the active site, where a binuclear zinc center orchestrates its hydrolysis. Unexpectedly, the structure unveilsbile acids bind the membrane enzyme, enhancing dimer assembly and enabling catalysis. These findings suggest NAPE-PLD might orchestrate a direct crosstalk betweenbile acids and lipid amide signals.[5]