Sphingolipidien

Sphingolipidien, or sphingolipids, are a class of lipids based on a sphingoid backbone (typically sphingosine) rather than glycerol. The fatty acid is linked to the amino group to form a ceramide, which serves as the common core for most sphingolipids. Variations in the head group and the acyl chain give rise to distinct subclasses, including sphingomyelins and glycosphingolipids, which populate cellular membranes, especially in neural tissue.

Biosynthesis and metabolism: de novo synthesis occurs in the endoplasmic reticulum from serine and palmitoyl-CoA via serine palmitoyltransferase, forming 3-ketosphinganine, then sphinganine, acylation to dihydroceramide, and desaturation to ceramide. Ceramide is the hub for further conversion into sphingomyelin (phosphocholine transfer) or glycosphingolipids (sugar residues). Degradation by sphingomyelinase, ceramidase, and kinases modulates levels of ceramide, sphingosine, and sphingosine-1-phosphate, which act as signaling molecules in various pathways.

Functions: Sphingolipids contribute to membrane structure and the formation of lipid rafts, affecting protein sorting and signaling. Ceramide and sphingosine-1-phosphate participate in stress responses, cell growth, differentiation, apoptosis, and immune signaling. Some glycosphingolipids reside in the outer membrane leaflet where they participate in cell recognition and pathogen interactions.

Clinical relevance: Abnormal sphingolipid metabolism underlies several lysosomal storage diseases, including Niemann-Pick disease (sphingomyelinase deficiency) and Gaucher and Fabry diseases (glucosylceramide and globotriaosylceramide accumulation, respectively). Altered sphingolipid signaling is linked to cancer, neurodegenerative disorders, and metabolic syndrome. Analytical approaches in lipidomics use mass spectrometry to quantify sphingolipid species in tissues and biofluids.