N-Acetyl-D-erythro-dihydrosphingosine

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