Immunological studies of propionyl CoA carboxylase in livers and fibroblasts of patients with propionic acidemia

Antiserum prepared against homogeneous pig heart propionyl CoA carboxylase cross-reacted with human propionyl CoA carboxylase, and was used to demonstrate the presence of immunological cross-reacting material in extracts from the livers of three patients and from fibroblasts of four patients with propionic acidemia representing three major propionyl CoA carboxylasedeficient genetic complementation groups, pcc A, pcc C and bio. Since the quantity of cross-reacting material in the propionyl CoA carboxylase-deficient livers and enzyme-deficient fibroblast cell lines was comparable to that in normal tissues while showing less than five percent of the normal enzyme activity, these patients must synthesize normal or near-normal quantities of an enzymatically inactive propionyl CoA carboxylase protein. In addition, no appreciable change in the amount of cross-reacting material was found in the biotin-responsive bio fibroblasts after incubation with supplemental biotin despite a sixteenfold increase in enzyme activity suggesting that the defect in the bio mutant involves the activation rather than the synthesis of a pre-existing normal apoenzyme.