Sphingolipids, especially sphingomyelin, constitute about 25% of the total lipid in the myelin sheath of nerve cells, where they protect and insulate these important cells. Sphingolipids are in a constant state of turnover (both synthesis and degradation). Degradation occurs in the lysosomes by a family of hydrolytic enzymes. When one or more of these enzymes is defective, congenital diseases called sphingolipidoses (also known as lipid storage diseases) occur. Table 19.1 lists some of these diseases and the defective enzyme(s) of each.
In each case, the disease arises from accumulation of an intermediate in sphingolipid metabolism. Tay-Sachs disease, one of the best known sphingolipidoses, arises from accumulation of ganglioside GM2 (Figure 19.16).
Gangliosides are receptors for specific agents, such as cholera toxin and influenza virus. Cholera toxin binds to ganglioside GM1, whereas influenza virus recognizes the sialic acid portion of certain gangliosides. The influenza virus then cleaves the gangliosides as part of its entry process into cells.
Some gangliosides promote the growth of neural tissue in cell culture, suggesting they might be used to promote regeneration of nerve tissue after spinal cord injury.
Ceramides have been proposed as a participant in the pathway leading to programmed cell death (apoptosis).
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