Application Notes:
N-Acetyl-D-erythro-dihydrosphingosine is a non-natural analog of the ceramide precursor dihydroceramide. This acetyl
dihydroceramide has properties and functions that are different from natural dihydroceramide and is therefore a useful tool
for studying dihydroceramides and ceramides. Whereas short chain ceramides potently induce apoptosis in cells neither short
nor long-chain dihydroceramides are able to do so.1 N-Acetyl-dihydroceramide has been shown to be incorporated into
mitochondria membranes at the same rate as N-acetyl-ceramide and at a greater rate than N-palmitoyl-ceramide. This
demonstrates that both dihydroceramide and ceramide insert into the mitochondrial membrane at the same rate indicating that
the inability of dihydroceramide to induce apoptosis is not due to a lack of its insertion into the membrane.2 The presence of
the 4–5 trans double bond is essential for ceramide-channel formation. Dihydroceramides are unable to form these ceramidechannels
due to their lack of a 4-5 double bond and it is suggested that this is the reason for its lack of apoptotic activity.3
Natural 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
dihydrosphingosine-1-phosphate and a decrease in other sphingolipids leading to a number of diseases including oesophageal
cancer. N-(4-Hydroxyphenyl) retinamide (4-HPR) has been tested as an anti-cancer agent. It inhibits the dihydroceramide
desaturase enzyme in cells resulting in a high concentration of dihydroceramide and dihydro-sphingolipids and this is thought
to be the cause of the anti-cancer effects.4
References:
1. F. Bi et al. “A Conserved Cysteine Motif Is Critical for Rice Ceramide Kinase Activity and Function” PLoS ONE 6(3): e18079.
doi:10.1371/journal.pone.0018079, 2011
2. L. Siskind et al. “Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations” Mitochondrion, vol. 6 pp. 118-
125, 2006
3. T. Goldkorn et al. “H2O2 acts on cellular membranes to generate ceramide signaling and initiate apoptosis in tracheobronchial epithelial cells” Journal of
Cell Science, vol. 111 pp. 3209-3220, 1998
4. W. Zheng “Fenretinide increases dihydroceramide and dihydrosphingolipids due to inhibition of dihydroceramide desaturase” Georgia Institute of
Technology, 2006