Dihydroceramide is a critical intermediate in the de novo synthesis of ceramide, leading to many complex sphingolipids. It is synthesized by the acylation of dihydrosphingosine and is subsequently converted to ceramide via the enzyme dihydroceramide desaturase or into phytosphingosine via the enzyme C4-hydroxylase.1 Inhibition of ceramide synthase by some fungal toxins (such as fumonisin B1) causes an accumulation of dihydrosphingosine and sphinganine-1-phosphate and a decrease in dihydroceramide and other dihydrosphingolipids, leading to a number of diseases including oesophageal cancer.2 The dihydroceramide desaturase inhibitor N-(4-Hydroxyphenyl)-retinamide (4-HPR) has been tested as an anti-cancer agent since it inhibits the dihydroceramide desaturase enzyme in cells resulting in a high concentration of dihydroceramide and dihydro-sphingolipids causing anti-cancer effects.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. J. Soriano et al. “Mechanism of action of sphingolipids and their metabolites in the toxicity of fumonisin B1” Progress in Lipid Research, Vol. 44 pp. 345-356, 2005
  3. W. Zheng “Fenretinide increases dihydroceramide and dihydrosphingolipids due to inhibition of dihydroceramide desaturase” Georgia Institute of Technology, 2006