The many faces (and phases) of ceramide and sphingomyelin II – binary mixtures

Abstract

A rather widespread idea on the functional importance of sphingolipids in cell membranes refers to the occurrence of ordered domains enriched in sphingomyelin and ceramide that are largely assumed to exist irrespective of the type of N-acyl chain in the sphingolipid. Ceramides and sphingomyelins are the simplest kind of two-chained sphingolipids and show a variety of species, depending on the fatty acyl chain length, hydroxylation, and unsaturation. Abundant evidences have shown that variations of the N-acyl chain length in ceramides and sphingomyelins markedly affect their phase state, interfacial elasticity, surface topography, electrostatics, and miscibility, and that even the usually conceived Bcondensed^sphingolipids and many of their mixtures may exhibit liquid-like expanded states. Their lateral miscibility properties are subtlety regulated by those chemical differences. Even between ceramides with different acyl chain length, their partial miscibility is responsible for a rich twodimensional structural variety that impacts on the membrane properties at the mesoscale level. In this review, we will discuss the miscibility properties of ceramide, sphingomyelin, and glycosphingolipids that differ in their N-acyl or oligosaccharide chains. This work is a second part that accompanies a previous overview of the properties of membranes formed by pure ceramides or sphingomyelins, which is also included in this Special Issue.

Structural basis for acyl chain control over glycosphingolipid sorting and vesicular trafficking

“…In nature, the cis -double bond in the GM1 species containing mono-unsaturated acyl chains of 16–22 hydrocarbons atoms in length is positioned at carbon atom 9 or 13 (Δ 9 and Δ 13 ) extending from the amide linkage to sphingosine, and thus located within the outer leaflet of the membrane bilayer. Within this area, the kink in the acyl chain caused by unsaturation interferes with alignment against the flat and rigid sterol structure of cholesterol ( Fanani and Maggio, 2017a , 2017b ; Jaikishan et al, 2010 ; Kihara, 2012 ; Ramstedt and Slotte, 1999 ; Stockton and Smith, 1976 ). These GM1 species entered endosome sorting tubules of the recycling and retrograde endosome pathways, and their trafficking was not dependent of cholesterol.…”

Structural basis for acyl chain control over glycosphingolipid sorting and vesicular trafficking

“…In nature, the cis-double bond in the GM1 species containing mono-unsaturated acyl chains of 16 to 22 hydrocarbons atoms in length is positioned at carbon atom 9 or 13 (Δ 9 and Δ 13 ) extending from the amide linkage to sphingosine, and thus located within the outer leaflet of the membrane bilayer. Within this area, the "kink" in the acyl chain caused by unsaturation interferes with alignment against the flat and rigid sterol structure of cholesterol (43,(70)(71)(72)(73)(74).…”

Small Molecule Inhibitors Targeting Biosynthesis of Ceramide, the Central Hub of the Sphingolipid Network

“…Sphingomyelin, the most abundant form of sphingolipids, is a non-glycerol-based phospholipid in which the primary alcohol of ceramide is linked to choline through a phosphodiester bond. , Sphingomyelin is synthesized from ceramide by sphingomyelin synthase in the Golgi apparatus. Because of varying chain length (C14 to C26) of the fatty acid moiety of the ceramide molecule, sphingomyelin occurs in a number of structurally different forms.…”