Adult Ascaris suum inhabits the small intestine of its swine host where oxygen tension is low. Despite the lack of oxygen, A. suum generates mitochondrial ATP by an NADH-requiring, inner membrane-associated (IM), electron transport-coupled fumarate reductase, producing succinate. Compelling data suggests that the “malic” enzyme resides in the mitochondrial intermembrane space (IMS), forming the NADH required for anaerobic phosphorylation. Thus, the transfer of reducing power from IMS NADH across the IM to matrix NAD+ would be needed to form the NADH required for anaerobic ATP generation. An IM-associated NADH→NAD+ transhydrogenation reaction has been implicated in this transfer and is thought to be a catalytic activity of lipoamide dehydrogenase in ascarid mitochondria. The purpose of this study was to ascertain whether the NADH→NAD+ transhydrogenation reaction in adult A. suum results from more than one catalytic activity, viz., lipoamide dehydrogenase and NADH dehydrogenase. Studies of the mitochondrial NADH→NAD+ transhydrogenation reaction, lipoamide dehydrogenase, and NADH dehydrogenase were performed using disrupted adult A. suum mitochondria as the source of enzymes. Based on studies evaluating the effects of pH on the ascarid activities, and the thermal labilities of these reactions, it appears that the lipoamide dehydrogenase and NADH dehydrogenase catalyze an NADH→NAD+ transhydrogenation reaction in adult A. suum mitochondria. These findings were supported further by intramitochondrial localizations of the three activities as well as the effects of inhibitors on these systems.
In light of these findings, it is concluded that the NADH→NAD+ transhydrogenation reaction in adult A. suum is the result of lipoamide dehydrogenase and NADH dehydrogenase systems. Presumably, these studies will aid in the ultimate development of specific chemotherapeutic strategies for development of anthelmintics.