Mechanism of the inhibition of aldehyde dehydrogenase in vivo by disulfiram and diethyldithiocarbamate.
Mechanism of the inhibition of aldehyde dehydrogenase in vivo by disulfiram and diethyldithiocarbamate.
复制标题
双硫仑和二乙基二硫代氨基甲酸酯体内抑制乙醛脱氢酶的机制。
作者：
R. Deitrich;V. Erwin
用NAD和醛产生NADH的速率测定了大鼠肝脏线粒体和上清液中的醛脱氢酶。虽然已知二硫仑在体外是比二乙基二硫代氨基甲酸酯更有效的醛脱氢酶抑制剂，但给大鼠服用这两种化合物都会导致这种动物肝脏中酶活性的降低。如果假定二乙基二硫代氨基甲酸乙酯在体内被再氧化为二硫仑，则得到非常相似的剂量-响应曲线。双硫仑给药后上清液和线粒体酶活性的下降和恢复在时间过程上是相同的。活性的恢复可被环己亚胺阻断。这些结果表明，双硫仑是体内醛脱氢酶的不可逆抑制剂。
Aldehyde dehydrogenase in rat liver mitochondria and supernatant fluid has been assayed by following the rate of NADH production from NAD and aldehyde. Although it is known that disulfiram is a much more potent inhibitor in vitro of aldehyde dehydrogenase than diethyldithiocarbamate, the administration of either compound to rats brings about a decrease in enzyme activity in the livers of such animals. Very similar dose-response curves are obtained if it is assumed that diethyldithiocarbamate undergoes reoxidation to disulfiram in vivo . The decrease and return of activity of the supernatant and mitochondrial enzymes after disulfiram administration are identical in time course. The return of activity can be blocked by cycloheximide. These results indicate that disulfiram is an irreversible inhibitor of aldehyde dehydrogenase in vivo .