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- The second aspect of metabolism we are studying is control of NAD and NADP levels within the cell. The vitamin niacin (B3) is a precursor to both NAD and NADP, which are essential for life in all organisms known. Together, these related cofactors serve in over 300 cellular reactions, several of which are central to basic metabolism. In addition to their roles as cofactors in metabolic reactions, NAD(P) also serve as allosteric regulators of many key metabolic reactions making control of NAD(P) levels critical to proper metabolic regulation. One of the key questions we are examining is why two very structurally related cofactor molecules have evolved (NAD and NADP differ by a single phosphate). It is thought these compounds arose in order to allow cells to differentially regulate metabolic process. In support of this hypothesis, NAD is primarily used for the production of cellular energy (ATP) while NADP is primarily used in reductive biosynthetic reactions that produce the molecular building blocks of the cell. Many of the pathways leading to the biosynthesis and recycling of NAD(P) have recently been described, however, several genes encoding key enzymes are still unknown. In addition, there are only laborious methods for accurately determining the levels of these compounds. We are interested in discovering the genes encoding NAD(P)-related functions as well as in measuring the internal levels of these compounds in response to growth conditions and mutation.
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