NMR Studies of Phoshate Metabolism in Protozoan Parasite

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DESCRIPTION (provided by applicant): The aim of this research is to use high field nuclear magnetic resonance spectroscopy to investigate the metabolic processes that occur in Trypanosoma cruzi and to use this information to help discover new drug targets. The methods to be employed for the further investigation of the metabolic processes in T cruzi involve the use of 600 and 750 MHz solution and solid-state NMR to study the 31P and 13C NMR spectroscopy of both epimastigote and amastigote forms. To date, initial 31P and 13C NMR spectra have been obtained, but the relationships between carbohydrate and phosphate metabolism, and amino acid and phosphate metabolism, have not been investigated. What needs to be done next, therefore, is to make the first correlations between carbon and phosphate metabolism, work that appears to be essential due to the very large levels of pyrophosphate found. That is, the role of pyrophosphate needs to be clarified. Here, the ability to monitor both soluble condensed phosphates (using solution NMR) as well as insoluble phosphates (using solid-state magic-angle sample-spinning techniques) should prove invaluable. Plus, solution and solid-state NMR techniques will be used to investigate the unusual poly-a-hydroxyoctanoate species found in T cruzi, which by analogy with the polyphosphate/poly-cx-hydroxybutyrate species found in prokaryotes may represent a primitive ion channel in the acidocalcisome.