Pathways and mechanisms of N-acylethanolamine biosynthesis: can anandamidebe generated selectively?

Long-chain N-acylethanolamines (NAEs) and their precursors, N-acylethanolam ine phospholipids, are ubiquitous trace constituents of animal and human ce lls, tissues and body fluids. Their cellular levels appear to be tightly re gulated and they accumulate as the result of injury. Saturated and monounsa turated congeners which represent the vast majority of cellular NAEs can ha ve cytoprotective effects while polyunsaturated NAEs, especially 20:4n-6 NA E (anandamide), elicit physiological effects by binding to and activating c annabinoid receptors. It is the purpose of this article to review published data on the pathways and mechanisms of NAE biosynthesis in mammals and to evaluate this information for its physiological significance. The generatio n and turnover of NAE via N-acyl PE through the transacylation-phosphodiest erase pathway may represent a novel cannabinoid receptor-independent signal ling system, analogous to and possibly related to ceramide-mediated cell si gnalling. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.