Molecular arrangements in sphingolipids. Conformation and hydrogen bonding of ceramide and their implication on membrane stability and permeability

The preferred conformation of the ceramide part of sphingolipids has been deduced from single crystal structures of a series of sphingolipid constituents: N-tetracosanoylphytosphingosine, glycosylphytosphingosine hydrochloride, sphingosine hydrochloride, triacetylsphingosine, DL-2-hydroxytetradecanoic acid and N-stearoylethanolamine. The amide group of the ceramide, which serves as a link between the hydrocarbon chains, has a basic significance for the contormation of the entire molecule. This rigid group, which comprises six atoms in a planar conformation, adopts a perpendicular orientation towards the axes of the two hydrocarbon chains. The carbonyl oxygen thereby turns into an eclipsed position with the hydrogen atoma at carbon atom 2 of the sphingosine. A parallel chain stacking is achieved by a sharp perpendicular bend of the fatty acid. This bend is produced by a sequence of two --60 degrees rotations about the C-C bonds at both sides of the alpha-carbon atom. The orientation of the hydrogen bond donors and acceptors of the amide group and the hydroxyl groups allow lateral interaction with other lipid molecules. The proposed models are supported by infrared spectra, thin-layer chromatographic behaviour and monolayer studies of synthetic model ceramides. The functional role of the hydrogen bonding groups in the ceramide part of sphingolipids is emphasized and their significance for the formation of lateral hydrogen bonds within the membrane layer and thereof arising effects on membrane stability and permeability are discussed.