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.