SYNTHESIS OF SPHINGOMYELIN BY OLIGODENDROCYTES - HOW AND WHERE

Sphingomyelin (SM) biosynthesis in cultured oligodendrocytes (OC) was evaluated: (i) with [C-14] tracers (choline, ethanolamine, serine) to pinpoint the major metabolic routes; (ii) with fluorescent and truncat ed, radiolabeled ceramide analogs to determine the relative activities of SM-synthase in intra- and extra-Golgi compartments of OC. In contr ast to a general contention in the literature that SM synthase is abse nt from the brain, our data show that (choline --> CDP-choline --> pho sphatidylcholine (PC) --> SM) is the major anabolic route with only a minor contribution to PC via methylation of phosphatidylethanolamine ( PE). SM synthase activity was found to be equally divided between intr a- and extra-Golgi compartments of OC. Moreover, significant SM-syntha se activity was recovered in purified myelin preparations. Our results shed new light on the possible involvement of sphingolipid-derived me diators in myelination.