Figure 1

Proposed biosynthetic pathways for the generation of AEA from its arachidonoyl containing NAPE (NArPE) precursor. NAPEs are formed from phosphatidyl choline and phosphatidyl ethanolamine membrane precursors by an as yet uncharacterised N-acyl transferase enzyme. The most widely accepted route of AEA biosynthesis is via NAPE-PLD [142, 143]. This enzyme is also responsible for the generation of other NAEs including OEA and PEA from their corresponding NAPE precursor. The serine hydrolase αβh4 can generate lysoNAPE and glycerophospho-N-acyl ethanolamine (GpNAE), including glycerophospho-N-arachidonoyl ethanolamine (GpAEA), glycerophospho-N-oleoyl ethanolamine (GpOEA) and glycerophospho-N-palmitoyl ethanolamine (GpPEA) intermediates that are subsequently hydrolysed by a metal dependant phosphodiesterase to produce AEA, OEA and PEA, respectively. In mouse brain, this enzyme has been identified as GDE1 [144]. LPS induced synthesis of AEA involves the generation of phosphorylated AEA (pAEA) via PLC which is then converted to AEA by phosphatases. In mouse brain, this phosphatase has been identified as PTPN22 [83]. Whether this third pathway contributes to the synthesis of other NAEs such as OEA and PEA remains to be determined.