Metabolism of succinonitrile in liver: studies on the systems involved in cyanide release.

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.