What Are Sphingolipids?

Structure and metabolism of sphingolipids

Recently, more than 300 species of sphingolipids have been identified and characterized as long-chain sheath-like base backbones. Ceramide is the aminoacylation product of sphingosine at the 2-carbon position, which has strong biological activity and is a basic structural unit of sphingolipids. The simplest forms of sphingolipids include phosphoceramides (containing a phosphate group) and cerebrosides (containing glucose and galactose). Other phosphorylated sphingolipids include phosphoethanolamine ceramide and sphingomyelin (SM). Most sphingolipids are derived from cerebrosides.

The biosynthesis of sphingolipids usually consists of serine and palmitoyl-CoA under the catalysis of serine-palmitoyltransferase to generate 3-ketodihydrosphingosine, which is subsequently reduced to dihydrosphingosine. Under the action of sphingosine N-acyltransferase, dihydroceramide is further generated, and finally, a trans double bond is formed at the 4 and 5 positions to synthesize ceramide. Ceramides are precursors for the synthesis of various sphingolipids within cells, which all perform specific functions. Sphingomyelin is located in the cell membrane of the myelin sheath on neurons. Glycosphingolipids are found in the cell membranes of muscle tissue. Gangliosides are sphingolipids linked to sugar chains such as sialic acid and are presented in the plasma membrane of cells.

Mechanistically, glycolipids and sphingolipids are degraded by hydratase enzymes to remove special polar head groups. For example, glycolipids hydrolyze glucose groups into cerebrosides by the action of glucosidase and are hydrolyzed into ceramides by cerebrosidase. Therefore, the synthesis of sphingolipids begins with serine and palmitoyl-CoA, followed by the addition of head groups of different polarities, and finally, these head groups are released to form fatty acids and derivatives.

The function of sphingolipids

Sphingolipids are essential structural components of cell membranes. Further discoveries have revealed the association of sphingolipids with signaling pathways related to the regulation of cell growth, differentiation, and death. Sphingolipids play important roles in various life processes, including tumor evolution, the development of multi-drug resistance in tumor cells, vascular endothelial cell signaling, atherosclerosis formation, regulating the development and lifespan of organisms, as well as viral and bacterial infections.

Various diseases can occur in the human body due to deficiency or excess of sphingolipids. The most commonly known example refers to Gaucher's disease. When Gaucher's disease is present, fatty substances can accumulate in internal organs, the brain and bones. Another prominent disease is Fabry's disease, which causes fatigue and kidney failure.

With the development of modern instrumentation techniques, especially mass spectrometry and chromatography-mass spectrometry, the separation and detection of sphingolipids have entered an era of rapid development. In order to promote the identification of sphingolipids and discover the biological function in disease development, including cancer, thus broadening therapeutic targets strategies, various sample processing and analysis techniques have been developed to detect sphingolipids in biological samples using mass spectrometry.

Creative Proteomics reserved extensive experience in lipid analysis. To better serve researchers in the pharmaceutical and clinical fields, Creative Proteomics is equipped with a nano-LC-MS/MS technology platform to provide high-quality sphingolipid identification and quantitative analysis services to advance disease mechanism research and related drug discovery processes.

Reference

Harden, O. C., & Hammad, S. M. (2020). Sphingolipids and diagnosis, prognosis, and organ damage in systemic lupus erythematosus. Frontiers in immunology, 2532.

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