Substrate Specificity for Ceramide in the Enzymatic Formation of Sphingomyelin

An enzymatic synthesis of sphingomyelin, N-acylsphingosylphosphorylcholine, was demonstrated by Sribney and Kennedy to occur via a reaction between ceramide (N-acylsphingosine) and CDP-choline. They indicated in this study that N-acyl derivatives of threo-sphingosine were far superior to the erythro derivatives as acceptors for the phosphorylcholine moiety. We have repeated these enzymatic experiments and obtained essentially identical results. The observation, however, appears to be inconsistent with the fact that the sphingosine moiety of ceramides and sphingomyelins existing in nature has the erythro configuration. Since this discrepancy could be ascribed to an enzymatic artifact, as discussed elsewhere, due to the fact that emulsification of threo-ceramides is more efficient than that of the erythro isomers, we decided to investigate the reaction further. The present communication describes experiments which indicate that under appropriate conditions not only threo-ceramides but also erythro-ceramides are active as substrates in the enzymatic formation of sphingomyelin.