Control of metabolic flux, the flow of metabolites through a complex metabolic network, is of importance to understand how an organism is sensing, and responding to, nutrient changes in its environment. Metabolic flux control can be measured for, and a control coefficient assigned to, each enzyme in a pathway. Measuring metabolic flux control in multicellular organisms is complicated by the fact that nutrient sensing and metabolic flux control may vary by tissue type. Major effects should be detectable in genomic information, as enzymes with high control coefficients will exhibit genetic patterns of adaptation when the pathway is under selection pressure. I used genetic variation within and among populations of Drosophila melanogaster, as well as divergence between D. melanogaster and the closely related D. simulans, to identify candidate genes for experimental study. I then conducted experiments with candidate genes using tissue specific RNA interference knockdown, focusing on two enzymes comprising the glycerophosphate shuttle in the context of starvation resistance, adipokinetic hormone (AKH) signaling, the Drosophila analog of glucagon signaling, and Insulin/Insulin-like signaling. None of the genes that I studied had a significant effect on starvation resistance when knocked down in Insulin-like protein secreting cells. I found that glycerophosphate oxidase, but not glycerophosphate dehydrogenase, significantly increased the average time to death in starvation conditions when knocked down in AKH secreting cells. Because the glycerophosphate shuttle is important in transferring nicotinamide adenine dinucleotide equivalents between the cytosol and inner matrix of the mitochondrion, this result implicates the coupling of reduction-oxidation state with AKH signaling.
|Commitee:||Gergen, John P., Harshman, Lawrence, True, John|
|School:||State University of New York at Stony Brook|
|School Location:||United States -- New York|
|Source:||DAI-B 77/06(E), Dissertation Abstracts International|
|Subjects:||Genetics, Evolution and Development|
|Keywords:||Adaptation, Metabolism, Starvation|
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