Ceramides Made from Sphingosines with Sphingoid Bases other than C18

Ceramides containing sphingosine bases other than the most prevalent C18:1 base are very useful in determining sphingosine metabolism and derivatives and as internal standards.1 Ceramide functions as a precursor in the synthesis of sphingomyelin, glycosphingolipids, sphingosine-1-phosphate, and free sphingosine. Ceramide exerts numerous biological effects, including induction of cell maturation, cell cycle arrest, terminal cell differentiation, cell senescence, and cell death.2 Two of ceramide’s metabolites, sphingosine-1-phosphate and glucosylceramide, produce cell proliferation and other cellular functions.3 Because of its functions, ceramide has been investigated for use in cancer treatment.4 Other effects include producing reactive oxygen in mitochondria (followed by apoptosis) and stimulating phosphorylation of certain proteins (especially mitogen activated protein). Ceramide also stimulates some protein phosphatases (especially protein phosphatase 2A) making it an important controller of protein activity. 2-hydroxy fatty acid ceramides are especially abundant in nervous and epidermal cells. These ceramides are important for the permeability barrier function of the epidermis and the lipid organization in membranes. Farber disease is an accumulation of ceramides due to a lack of activity of the lysosomal enzyme acid ceramidase.

References:

  1. N. Zitomer et al. “A single extraction method for the analysis by liquid chromatography/tandem mass spectrometry of fumonisins and biomarkers of disrupted sphingolipid metabolism in tissues of maize seedlings” Analytical & Bioanalytical Chemistry, Vol. 391 pp. 2257-2263, 2008
  2. J. M. Hauser, B. M. Buehrer, and R. M. Bell “Role of ceramide in mitogenesis induced by exogenous sphingoid bases.” Journal of Biological Chemistry, Vol. 269 pp. 6803, 1994
  3. N. S. Radin, “Killing tumours by ceramide-induced apoptosis: a critique of available drugs” Biochemical Journal, Vol. 371 pp. 243-256, 2003
  4. N. S. Radin, “Designing anticancer drugs via the achilles heel: ceramide, allylic ketones, and mitochondria” Bioorganic and Medicinal Chemistry, Vol. 11(10) pp. 2123-2142, 2003