Synthesis of ceramides and cerebrosides in rat brain: comparison with synthesis of lignoceroyl-coenzyme A.

ABSTRACT

The ?-hydroxylation and conversion of lignoceric acid into ceramide, cerebroside, and water-soluble products in particulate fractions from rat brain was studied in the presence of sphingosine and UDP-galactose, with particular reference to the effects of CoA and the synthesis of lignoceroyl-CoA. The synthesis of lignoceroyl-CoA was found to be almost completely dependent on the addition of exogenous CoA, whereas the formation of water-soluble products, mostly glutamate, was stimulated by, but was not stringently dependent on the addition of CoA. In contrast to these two metabolic pathways, both the synthesis of ceramides and cerebrosides and ?-hydroxylation were unaffected by the addition of CoA. While removal of sphingosine and UDP-galactose had drastic effects on the sphingolipid synthesis, COA did not have any effect on the removal. On the other hand, removal of sphingosine resulted in a significant increase of the synmthesis of lignoceroyl-CoA and moderate increase in the formation of water-soluble products. These observations further indicated that CoA ester formation may not be required for the synthesis of these sphingolipids, and suggest that there may be two pathways for oxidative degradation of lignoceric acid in brain-one CoA-dependent and the other CoA-independent.