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Ceramide

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  • Ceramides (pronounced ser-A-mid OR seramide) are a family of lipid molecules. A ceramide is composed of sphingosine and a fatty acid.

  • Ceramides are found in high concentrations within the cell membrane of cells. They are one of the component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer.

  • The most well-known functions of ceramides as cellular signals include regulating the differentiation, proliferation, programmed cell death (PCD), and apoptosis (Type I PCD) of cells.

  • There are three major pathways of ceramide generation. The sphingomyelinases pathway uses an enzyme to break down sphingomyelin in the cell membrane and release ceramide. The de novo pathway creates ceramide from less complex molecules.

  • Ceramide generation can also occur through breakdown of complex sphingolipids that are ultimately broken down into sphingosine, which is then reused by reacylation to form ceramide. This latter pathway is termed the Salvage pathway.

  • Ceramides are formed as the key intermediates in the biosynthesis of all the complex sphingolipids, in which the terminal primary hydroxyl group is linked to carbohydrate, phosphate etc.

  • The distinctive ceramides in the skin are derived mainly from glucosylceramide synthesized in specific organelles termed 'lamellar bodies' in the epidermal cells.

  • As a bioactive lipid, ceramide has been implicated in a variety of physiological functions including apoptosis, cell growth arrest, differentiation, cell senescence, cell migration and adhesion.

  • Ceramides are also produced during the catabolism of the complex sphingolipids, for example by the action of one or other of the sphingomyelinases or of phospholiphase on sphingomyelin in animal tissues as part of the sphingomyelin cycle.

  • Ceramides, like other lipid second messengers in signal transduction, are produced rapidly and transiently in response to specific stimuli in order to target specific proteins.

  • Because of its apoptosis-inducing effects in cancer cells, ceramide has been termed the "tumor suppressor lipid".

  • Several studies have attempted to define further the specific role of ceramide in the events of cell death and some evidence suggests ceramide functions upstream of the mitochondria in inducing apoptosis.

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