Grants and Contracts Details
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.
Status | Finished |
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Effective start/end date | 4/1/13 → 3/31/15 |
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