Peripheral nerve sphingomyelin and cerebroside are both formed via two metabolically and kinetically distinct...

We have studied the labeling kinetics of peripheral nerve sphingolipids in vivo. The kinetic analysis of the labeling profiles observed for the various sphingolipids demonstrated that 90% of cerebrosides, but only 30% of sphingomyelin, were synthesized via a de novo synthesized ceramide intermediate following the injection of 1-4 pmol [3H]palmitate into mouse sciatic nerves. The remaining sphingolipid labeling (30% of the total) was due to direct acylation events, using free fatty acids originating from a pool different from those implicated in the de novo ceramide pathway. Direct acylation events ceased within 1 h following substrate administration, while labeling via the ceramide pathway continued through 5 h. The results provide the first in vivo demonstration that the formation of cerebrosides and sphingomyelin in peripheral nerves in situ can be simultaneously assured via two metabolically and kinetically distinct pathways that employ different fatty acid pools.