Glucan phosphatases in neurodegeneration and plant starch metabolism

  • Gentry, Matthew (PI)
  • Raththagala, Madushi (CoI)

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Description

Biofuels research and research into the fatal neurodegenerative disease called Lafora disease (LD) are intimately linked by a newly described family of enzymes called glucan phosphatases. Glucans are the most abundant polymer in plants and algae, with cellulose (â-1-4 linkages) serving as the major structural component and starch (á-1-4 and á-1-6 linkages) as the major energy reserve. Due to its abundance and energy-rich status, starch is a common 1st generation biofuels feedstock. Instead of starch, humans utilize glycogen as their primary carbohydrate energy storage molecule. Both starch and glycogen metabolism is dependent on the action of glucan phosphatases. Plants release the energy in starch via a recently identified three-step process: starch phosphorylation, degradation, and dephosphorylation. Plants phosphorylate the outer starch glucose units to make them water-soluble and enzyme accessible so that amylases can degrade the starch into glucose. Following amylase activity, the phosphate must be removed by glucan phosphatases. This three-step cycle is repeated to allow efficient, processive starch degradation. In the absence of phosphorylation or dephosphorylation, the amylases are very inefficient and plants are unable to degrade the starch that it produces. In humans, glycogen synthase erroneously introduces a phosphate group ~1/10,000 glucose units. The human glucan phosphatase laforin removes phosphate from glycogen. In the absence of laforin activity, glycogen transforms into a hyperphosphorylated, water-insoluble, starch-like Lafora body (LB). LBs are the suspected cause of neuronal apoptosis and eventual death of LD patients. While much progress has been made concerning the biology of reversible starch phosphorylation little is known about the molecular mechanisms regulating glucan phosphatase function. The work in this proposal addresses critical information gaps of this essential pathway. We propose to define the function, structures, and regulation of both plant and human glucan phosphatases. Completion of this proposed work will define this novel enzyme family and impact both biofuels research and the field of neurodegeneration.
StatusFinished
Effective start/end date4/1/133/31/15

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