N‐Myristoylethanolamine–cholesterol (1:1) complex: first evidence from differential scanning calorimetry, fast‐atom‐bombardment mass spectrometry and computational modelling

Abstract

The interaction of N-myristoylethanolamine (NMEA) with cholesterol is investigated by di¡erential scanning calorimetry (DSC), fast-atom-bombardment mass spectrometry (FAB-MS) and computational modelling. Addition of cholesterol to NMEA leads to a new phase transition at 55 ‡C besides the chain-melting transition of NMEA at 72.5 ‡C. The enthalpy of the new transition increases with cholesterol content up to 50 mol%, but decreases thereafter, vanishing at 80 mol%. The enthalpy of the chain-melting transition of NMEA decreases with an increase in cholesterol; the transition disappears at 50 mol%. FAB-MS spectra of mixtures of NMEA and cholesterol provide clear signatures of the formation of {[NMEA+choles-terol] + } {[NMEA+cholesterol+Na] + }. These results are consistent with the formation of a 1:1 complex between NMEA and cholesterol. Molecular modelling studies support this experimental ¢nding and provide a plausible structural model for the complex, which highlights multiple H-bond interactions between the hydroxy group of cholesterol and the hydroxy and carbonyl groups of NMEA besides appreciable dispersion interaction between the hydrocarbon domains of the two molecules. ß

Confocal microscopy and biochemical analysis reveal spatial and functional separation between anandamide uptake and hydrolysis in human keratinocytes

“…Overall, these data seem to favor the 'endocytic hypothesis' proposed by McFarland et al [41], and suggest that AEA uptake may benefit from a lipid environment enriched in cholesterol and CAV-1. Incidentally, a direct interaction of cholesterol with AEA, already reported for other N-acyl-hanolamines [44], might further contribute to enhance the transport process.…”

Synthesis, calorimetric studies, and crystal structures of N, O-diacylethanolamines with matched chains

“…X-ray diffraction measurements were carried out at room temperature (ca. 25°C) with combating stress and signaling events in animals and plants, several groups including ours have investigated the biophysical properties of NAPEs and NAEs and characterized their interaction with other membrane lipids (10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

Molecular packing and intermolecular interactions in two structural polymorphs of N-palmitoylethanolamine, a type 2 cannabinoid receptor agonist

“…Additionally, we have also reported the crystal structure of NMEA and analyzed the intermolecular interactions and molecular packing in the crystal lattice (29). Studies using DSC, fast-atom bombardment mass spectrometry, and computational modeling have indicated that NMEA forms a 1:1 (mol/mol) complex with cholesterol (30). In another study, the interaction of NPEA with dipalmitoylphosphatidylcholine was investigated by DSC, 31 P-NMR, and smallangle X-ray scattering (31).…”