The importance of hydrogen bonding in sphingomyelin's membrane interactions with co-lipids

• The hydrogen bonding properties of sphingomyelin (SM) are discussed.
• Both intra- and intermolecular H-bonds important for SM properties
• Cholesterol modulates and enhances intermolecular H-bonding of SM.
• Ceramide self-association is markedly affected by SM H-bonding.

Sphingomyelin is an important constituent of mammalian cell membranes. Its molecular structure is N-acyl-d-erythro-sphingosylphosphorylcholine. The N-acyls in sphingomyelin often contain 16–24 carbons that are mostly saturated chains; however, the monounsaturated 24:1Δ15c acyl chain is also common. In addition to the more saturated nature of sphingomyelins, compared to physiologically relevant glycerophospholipids, also their hydrogen bonding properties are very different from the glycerophospholipids. Sphingomyelins form extensive intramolecular hydrogen bonds (from the 3OH of the long-chain base to phosphate oxygens of the head group), but also intermolecular hydrogen bonding involving the NH of the long-chain base are important for sphingomyelin (and sphingolipid) properties in membrane environments. Hydrogen bonding involving sphingomyelin has been shown to markedly stabilize interactions with both cholesterol and ceramide in fully hydrated bilayers. Such interactions contribute to the propensity of saturated sphingomyelin to form a liquid-ordered phase together with cholesterol, or a gel phase with saturated ceramides. The purpose of this review is to present recent experimental and computational evidence in support of the importance of hydrogen bonding for the interaction of sphingomyelin with other membrane lipids.

Atoms of sphingomyelin involved in hydrogen bondingFigure optionsDownload high-quality image (51 K)Download as PowerPoint slide