2-Hydroxy Dihydroceramides

Dihydroceramide is a critical intermediate in the synthesis of many complex sphingoid bases. Inhibition of dihydroceramide synthesis by some fungal toxins that have a similar structure causes an increase in dihydrosphingosine and sphinganine-1-phosphate and a decrease in other sphingolipids leading to a number of diseases including oesophageal cancer. Dihydroceramide, synthesized by the acylation of dihydrosphingosine, is subsequently converted into ceramide via a desaturase enzyme or into phytosphingosine via the C4-hydrozylase enzyme.1 The presence of a hydroxyl group on the fatty acyl chain of dihydroceramides significantly affects the function and properties of the lipid. While 2(S)-hydroxydihydroceramides can be converted to non-hydroxydihydroceramides in vivo, 2(R)-hydroxydihydroceramides cannot. Data presented suggests that 2(R)-hydroxydihydroceramides may interact with some distinct cellular regulatory targets in a specific and more effective manner than their nonhydroxylated analogs.2 2-hydroxydihydroceramides have been shown to be incorporated into the galactosylceramides and sulfatides of the myelin where they are essential to neuronal functions.3

References:

  1. Y. Mizutani, A. Kihara, and Y. Igarashi “Identifcation of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation” FEBS Letters, vol. 563 pp. 93-97, 2004
  2. Z. Szulc et al. “Synthesis, NMR characterization and divergent biological actions of 2-hydroxy-ceramide/dihydroceramide stereoisomers in MCF7 cells” Bioorg Med Chem, vol. 18 pp. 7565-7579, 2010
  3. M. Kruer et al. “Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA)” Annals of Neurology, vol. 68 pp. 611-618, 2010