The long-term administration of L-cycloserine to mice: specific reduction of cerebroside level.
Short-term experiments in which L-cycloserine, the inhibitor of 3-ketodihydrosphinogosine synthase, was injected subcutaneously in young mice have shown that cerebroside synthesis is inhibited specifically. Studies on the effect of long term L-cycloserine treatment on sphingolipid synthesis were performed to determine whether mice could tolerate continued cerebroside reduction and whether or not the synthesis of other sphingolipids would be inhibited. L-cycloserine, when injected at a low dose for a period of two months resulted in significantly reduced brain cerebroside level with little or no reduction in sulfatide, ganglioside, or sphingomyelin levels; liver and spleen glucocerebroside levels were also significantly reduced. The rate of cerebroside synthesis in brain was greatly reduced, whereas synthesis of sulfatides was much less affected by L-cycloserine indicating that a portion of newly synthesized galactocerebroside is shunted to synthesis of sulfatides.
Sundaram
K S
KS
Dept. of Microbiology, CUNY Medical School, NY 10031.
Lev
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002554:Cerebrosides / Q000378:metabolism*; D003523:Cycloserine / Q000008:administration & dosage*; D006017:Glycolipids / Q000378:metabolism; D008297:Male; D051379:Mice; D013107:Sphingolipids / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000378:metabolism
D002554:Cerebrosides; D006017:Glycolipids; D013107:Sphingolipids; D013433:Sulfoglycosphingolipids; D003523:Cycloserine