This website was constructed as a class project for Genetics 564, an undergraduate Genetics course at UW-Madison.
Conclusions and Future Research
While a great deal is known about aldolase B and HFI, there is still a great deal more to investigate. Aldolase B protein interaction networks indicate that many interactions are only currently predictions. Investigating these further could reveal more about the function of aldolase B and possibly HFI. Furthermore, researching homology of species and narrowing investigation down to smaller regions of the aldolase B protein, such as the LCR and the C-terminus, could give more knowledge about the protein's properties. The role of aldolase B in fructose metabolism is understood, but learning more about the interactions and sites within the protein could further expand the current understanding of it. This, in turn, could expand our current knowledge base of HFI, possibly even leading to a dietary supplement that could allow individuals with HFI to consume fructose without experiencing unpleasant fructose-induced symptoms.
Future Direction 1: Comparing mouse and zebrafish aldolase B protein to aldolase B in other homologs.
Mouse and zebrafish are both missing the C-terminus region and the LCR in their aldolase B protein, whereas this is well-conserved in other homologs. It would be interesting to identify why this is, and how that contributes to other differences in fructose metabolism between these homologs. Using the String Database could be useful in starting this investigation since differences in protein interaction networks could indicate the reason for a genetic and or metabolic discrepancy.
Mouse and zebrafish are both missing the C-terminus region and the LCR in their aldolase B protein, whereas this is well-conserved in other homologs. It would be interesting to identify why this is, and how that contributes to other differences in fructose metabolism between these homologs. Using the String Database could be useful in starting this investigation since differences in protein interaction networks could indicate the reason for a genetic and or metabolic discrepancy.
Comparing mouse and zebrafish aldolase B protein interaction networks from the String Database to the human network. Proteins shown to interact with each other in String are circled in red.
Future Direction 2: Identifying the significance of alanine in the LCR. The LCR is alanine-rich, and this could be responsible for the LCR's possible role in enzymatic folding of the aldolase B protein. By switching out alanine for another amino acid, it could be determined whether alanine is required for the LCR to maintain its properties in enzymatic folding.
Future Direction 3: Continuing to test chemicals identified as effective in rescuing fructose metabolism in Specific Aim 1. Any chemical identified as effective in restoring fructose metabolism in Drosophila could be subject to further chemical testing in order to make progress toward developing a dietary supplement like Lactaid, a supplement that lactose intolerant individuals take to avoid symptoms caused by dairy consumption. A supplement like this for individuals with HFI could loosen dietary restrictions and reduce the deleterious effects of accidental fructose consumption. Priorities in chemical testing would be efficacy, safety, and feasibility of production.