Inhibition of Sphingolipid Synthesis by Cycloserine In Vitro and In Vivo
Inhibition of Sphingolipid Synthesis by Cycloserine In Vitro and In Vivo
复制标题
环丝氨酸体外和体内抑制鞘脂合成
DOI：
10.1111/j.1471-4159.1984.tb02716.x
复制
发表时间：
1984
影响因子：
4.7
通讯作者：
M. Lev
中科院分区：
文献类型：
--
作者：
K. Sundaram;M. Lev
摘要：在一项使用细菌和脑微粒体酶的研究中，d-和l-环丝氨酸被证明是鞘脂途径的第一种酶3-酮二氢鞘氨醇合成酶的不可逆抑制剂，l-环丝氨酸在体外对脑微粒体酶的抑制作用比d-异构体高100倍。在体内，l-环丝氨酸导致70%的脑微粒体酶抑制。一次注射后，酶活性在16小时后恢复正常的80%。腹膜内注射方案中每日剂量的l-环丝氨酸持续7天导致总脑神经节苷脂和神经节苷脂+硫苷脂水平显著降低。
Abstract: 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 intraper‐itoneal injection for 7 days caused a significant reduction in total brain ganglioside and cerebroside plus sulfatide levels.