The research proposed entails an investigation of the physiological impact of the pyridine nucleotide transhydrogenases on the energetics of the parasitic helminths. Numerous parasitic helminths have been found to differ significantly from their mammalian hosts in that the parasites are essentially anaerobic with respect to energy generation. Significantly, the helminth transhydrogenases appear to play a critical role in the vital process of anaerobic, electron transport-coupled, ATP generation by the helminths. More specifically, these mitochondrial transhydrogenases would act to link malate utilization by the organelles with ATP production via the electron transport mechanism. The proposed investigations are biochemical in nature and will aid in determining the physiological impact of the helminth transhydrogenases on anaerobic energetics and in characterizing these interesting, membrane associated enzymes using adult Hymenolepis diminuta as a model. Other helminth systems will also be investigated. The transhydrogenases of the helminths appear to differ from those of corresponding mammalian systems and such differences indicate that the helminth transhydrogenases represent vulnerable sites for potential chemotherapeutic attack. Certainly, specific disruption of the helminth transhydrogenases would limit severely energy generation leading to the destruction of the parasite.
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