Floreani M, Carpenedo F, Santi R, Contessa A R
Eur J Drug Metab Pharmacokinet. 1981;6(2):135-40. doi: 10.1007/BF03189480.
The liberation of cyanide from succinonitrile has been studied to obtain information on the cellular systems responsible for the release of this metabolite. 1) Using isolated endoplasmic reticulum preparations a complex between succinonitrile and cyt. P 450 has been detected. This finding together with the inhibition of cyanide liberation by SKF-525A in liver slices indicates that the endoplasmic reticulum is involved in the early stages of succinonitrile metabolism. 2) The decreased metabolism of succinonitrile which was observed after addition of inhibitors of oxidative phosphorylation indicates that an energy-dependent mitochondrial step might be involved in the subsequent steps. 3) It is concluded that cyanide liberation from succinonitrile is a multistep process in which the mitochondrial membrane and the endoplasmic reticulum are involved. The requirement for cellular integrity in order to accomplish the process of succinonitrile metabolism suggests other components or equilibria that are difficult to reproduce in in vitro experiments.
为了获取有关负责释放这种代谢物的细胞系统的信息，人们对丁二腈中氰化物的释放进行了研究。1）使用分离的内质网制剂，已检测到丁二腈与细胞色素P 450之间形成复合物。这一发现以及SKF - 525A对肝切片中氰化物释放的抑制作用表明，内质网参与了丁二腈代谢的早期阶段。2）添加氧化磷酸化抑制剂后观察到丁二腈代谢减少，这表明能量依赖性线粒体步骤可能参与后续步骤。3）得出的结论是，丁二腈中氰化物的释放是一个多步骤过程，其中涉及线粒体膜和内质网。完成丁二腈代谢过程对细胞完整性的要求表明存在其他难以在体外实验中重现的成分或平衡。
