The Sphinx of lipids


Sphingolipids constitute a class of lipids defined by their eighteen carbon amino-alcohol backbones which are synthesized in the ER from nonsphingolipid precursors. Modification of this basic structure is what gives rise to the vast family of sphingolipids that play significant roles in membrane biology and provide many bioactive metabolites that regulate cell function. This class of lipids and the cell metabolism addressing their synthesis and catabolism is very well described in a great review by Gault CR and colleagues.

Despite the diversity of structure and function of sphingolipids, their creation and destruction are governed by common synthetic and catabolic pathways. In this regard, sphingolipid metabolism can be imagined as an array of interconnected networks that diverge from a single common entry point and converge into a single common breakdown pathway.

Ceramide is the core of sphingolipid metabolism and the basic brick of each sphingolipid molecule. Ceramide, due to the differing acyl CoAs that can be used to produce it, is technically a class of molecules rather than a single molecule and therefore may have different biological functions depending on the acyl chain it is composed of.

At the apex of complexity are the glycosphingolipids (GSL) which contain dozens of different sphingolipid species differing by both the order and type of sugar residues attached to their headgroups. Since these molecules are produced from ceramide precursors, they too may have differences in their acyl chain composition, revealing an additional layer of variation.

Far more abundant are the sphingomyelin species which are produced in parallel with glycosphingolipids, however they are defined by a phosphocholine headgroup rather than the addition of sugar residues. Although sphingomyelin species all share a common headgroup, they too are produced from a variety of ceramide species and therefore can have differing acyl chains attached to their C-2 amino groups. Whether or not the differing acyl chain lengths in SMs dictate unique functions or important biophysical distinctions has not yet been established.

Sphingolipids are a diverse group of lipids which serve a variety of functions in both mammalian development and physiology. Only a few of these functions have been highlighted so far. New functions for sphingolipids in mammalian physiology continue to be discovered each year and will likely increase as our understanding of sphingolipid biology in whole organisms improves.

Happy Culturing!!!

Remembrane’s Team

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