Inhibition of sphingolipid synthesis by cycloserine in vitro and in vivo.
D- and L-cycloserine were shown to be irreversible inhibitors of the first enzyme of the sphingolipid pathway, 3-ketodihydrosphingosine synthetase, in a study using bacterial and brain microsomal enzymes. L-Cycloserine was shown to be 100 times more inhibitory than the D-isomer for the brain microsomal enzyme in vitro. In vivo, L-cycloserine caused a 70% inhibition of brain microsomal enzyme. Following one injection, enzyme activity recovered 80% of normal after 16 hours. Daily dosages of L-cycloserine on a regimen of intraperitoneal injection for 7 days caused a significant reduction in total brain ganglioside and cerebroside plus sulfatide levels.
D000818:Animals; D001439:Bacteroides / Q000201:enzymology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002554:Cerebrosides / Q000378:metabolism; D003523:Cycloserine / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008861:Microsomes / Q000201:enzymology*; D007652:Oxo-Acid-Lyases / Q000037:antagonists & inhibitors*; D013107:Sphingolipids / Q000096:biosynthesis*; D013217:Starvation; D013237:Stereoisomerism; D013433:Sulfoglycosphingolipids / Q000378:metabolism
D002554:Cerebrosides; D013107:Sphingolipids; D013433:Sulfoglycosphingolipids; D003523:Cycloserine; C021473:3-ketodihydrosphingosine synthetase; D007652:Oxo-Acid-Lyases