Recovery of ornithine decarboxylase activity after inhibition with alpha-difluoromethylornithine.

alpha-Difluoromethylornithine is an effective inhibitor of polyamine biosynthesis because of its specificity for ornithine decarboxylase and the fact that its attachment to this enzyme is considered to be irreversible. We have found, however, that ornithine decarboxylase inactivated with this inhibitor in intact cells, as well as purified enzyme inactivated in vitro, both are capable of releasing this inhibitor and recovering enzyme activity. This reactivation can be initiated by freezing of inactivated enzyme samples in the presence of reducing agents at -7 or -20 degrees C and can be partially induced at 37 degrees C. These results reveal an unexpected lability of this enzyme-inhibitor complex that needs to be considered in future experimental designs.