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


  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