Abstract
A large number of lipid molecules derived from phospholipids and fatty acids are known to function
as endogenous signaling molecules and are collectively referred to as lipid mediators. Ethanolamides
of long-chain fatty acids, called N-acylethanolamines, form a class of lipid mediators and include
arachidonoylethanolamide (anandamide), palmitoylethanolamide, and oleoylethanolamide, which act
as an endogenous agonist of cannabinoid receptors, an anti-inflammatory substance, and an appetitesuppressing
substance, respectively. In mammalian tissues, N-acylethanolamines are formed from phosphatidylethanolamine (PE) via N-acyl-PE, a “triacyl-type” phospholipid, by the sequential catalyses of
two enzymes, N-acyltransferase and N-acyl-PE-hydrolyzing phospholipase D (NAPE-PLD). We purified NAPE-PLD from rat heart and cloned its cDNA ahead of others in the world. We also found that a group
of proteins showed Ca2+-independent N-acyltransferase activity and proposed to rename these proteins “phospholipase A/acyltransferase (PLAAT)-1–5”. As for the degradation pathway, N-acylethanolamines
are hydrolyzed to free fatty acids and ethanolamine by fatty acid amide hydrolase. Our research group
discovered a second enzyme catalyzing the same reaction and named the enzyme “N-acylethanolaminehydrolyzing
acid amidase (NAAA)”. NAAA was a new lysosomal hydrolase abundantly expressed in
macrophages and prostate. In this review, I discuss our longstanding efforts towards the discovery, cDNA
cloning, and characterization of NAAA, NAPE-PLD, and PLAAT-1–5.
