Journal of Lipid Research, Vol 29, 1475-1479, Copyright © 1988 by Lipid Research, Inc.
Warfarin administration reduces synthesis of sulfatides and other sphingolipids in mouse brain
KS Sundaram and M Lev
CUNY Medical School, NY 10031.
The modulation of phosphosphingolipid synthesis by vitamin K depletion has
been observed in the vitamin K-dependent microorganism, Bacteriodes levii.
When cultured briefly without the vitamin, a reduction occurred in the
activity of the first enzyme of the sphingolipid pathway, 3-
ketodihydrosphingosine synthase. In this report, 16-day-old mice were
treated with the vitamin K antagonist, warfarin. Brain microsomes from
these animals showed a 19% reduction in synthase activity. Mice treated
with warfarin for 2 weeks showed a major reduction in sulfatide level
(42%), with a lesser degree or no reduction in levels of gangliosides and
cerebrosides. In further experiments, mice were treated with warfarin for 2
weeks and a group was then injected with vitamin K1 (aquamephyton) for 3
days. Enzyme activity returned to a normal level within 2-3 days. Sulfatide
levels had increased 33% in the vitamin K- injected group and ganglioside
levels also increased, where levels of cerebrosides and sphingomyelin
declined. Sulfatide synthesis determined by [35S] sulfate incorporation,
showed a 52% increase in incorporation following administration of vitamin
K for 3 days. These results suggest a role for vitamin K in the
biosynthesis of sulfatides and other sphingolipids in brain. This putative
role could be by post- translational protein modification analogous to the
role of vitamin K in other systems.