2-Hydroxy Ceramides

2-hydroxy fatty acyl ceramides are important for the permeability barrier function of the epidermis and lipid organization in membranes. These ceramides are especially abundant in nervous and epidermal cells. The 2-hydroxylation is catalyzed by fatty acid 2-hydroxylase. Ceramides function as precursors in the synthesis of sphingomyelin, glycosphingolipids, and of free sphingosine and fatty acids. Two ceramide metabolites, sphingosine-1-phosphate and glucosylceramide, produce cell proliferation along with other cellular functions.1 Ceramides exert numerous biological effects including induction of cell maturation, cell cycle arrest, terminal cell differentiation, cell senescence, and cell death.2 Because of its functions, ceramides have been investigated for use in cancer treatment.3 Other effects include producing reactive oxygen in mitochondria (followed by apoptosis) and stimulating phosphorylation of certain proteins (especially mitogen-activated protein). Ceramides also stimulate some protein phosphatases (especially protein phosphatase 2A) making them an important controller of protein activity. Farber disease is an accumulation of ceramides due to a lack of activity of the lysosomal enzyme acid ceramidase.

References:

  1. 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
  2. N. S. Radin, “Killing tumours by ceramide-induced apoptosis: a critique of available drugs” Biochemical Journal, Vol. 371 pp. 243-256, 2003
  3. 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