Presence and potential signaling function of N-acylethanolamines and their phospholipid precursors in the yeast Saccharomyces cerevisiae

Abstract N -Acylethanolamines (NAEs) and N -acylphosphatidylethanolamines (NAPEs) are trace constituents of vertebrate cells and tissues and much is known about their metabolism and possible function in animals. Here we report for the first time the identification and quantification of NAEs and NAPEs in several strains of the yeast Saccharomyces cerevisiae . Gas chromatography-mass spectrometry of appropriate derivatives revealed 16:0, 16:1, 18:0 and 18:1 N -acyl groups in both NAE and NAPE whose levels, in wild-type cells, were 50 to 90 and 85 to 750 pmol/μmol lipid P, respectively (depending on the phase of growth). NAPE levels were reduced by 45 to 60% in a strain lacking three type B phospholipases, suggesting their involvement in NAPE synthesis by their known transacylation activity. A yeast strain lacking the YPL103c gene, which codes for a protein with 50.3% homology to human NAPE-specific phospholipase D, exhibited a 60% reduction in NAE, compared to wild-type controls. The exposure of various yeast strains to peroxidative stress, by incubation in media containing 0.6 mM H 2 O 2 , resulted in substantial increases in NAE. Because yeast cells lack polyunsaturated fatty acids, they offer a useful system for the study of NAE generation and its potential signaling and cytoprotective effects in the absence of polyunsaturated (“endocannabinoid”) congeners.