Metabolism of peripheral nerve monogalactosylceramides

The metabolism of hydroxy galactocerebrosides (GalCe-OH) and nonhydroxy galactocerebrosides (GalCe) was investigated during nerve development, degeneration and regeneration by endoneurial injection of [14C]acetate and by in vitro incubation of rat sciatic endoneurium with [14C]acetate, [3H]galactose or [3H]glucose. After endoneurial microinjection, [14C]acetate was found to be incorporated first into GalCe-OH and later, and to a much lesser degree, into GalCe. The ratio of 14C-labeled GalCe-OH to GalCe decreased with time and remained fairly constant after 4 hr. On the other hand, in vitro incorporation of [14C]acetate resulted in higher 14C-labeling in GalCe and monogalactosyl diacylglycerol (MGDG) and lower 14C-labeling in GalCe-OH, diminishing with incubation time. After 24 hr, only GalCe and MGDG were labeled. When [3H]galactose or [3H]glucose, instead of [14C]acetate, were used as precursor in vitro, a similar preference for labeling of GalCe-OH was demonstrated in regenerating nerve. These data suggest that hydroxy fatty acids and hydroxy ceramides are the preferred substrates in peripheral nervous system for the sphingosine acyltransferase and the UDP-galactose:ceramide galactosyltransferase reactions, respectively. The alpha-hydroxylation system did not appear to be fully functional under in vitro conditions. The biosynthesis of GalCe-OH was greatly enhanced during nerve fiber regeneration and decreased rapidly with increasing age. This suggests that a close interrelation exists between alpha-hydroxylation and peripheral nerve myelination.