PERIPHERAL-NERVE SPHINGOMYELIN AND CEREBROSIDE ARE BOTH FORMED VIA 2 METABOLICALLY AND KINETICALLY DISTINCT PATHWAYS IN-VIVO

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