TY - JOUR
T1 - Phosphate incorporation during glycogen synthesis and Lafora disease
AU - Tagliabracci, Vincent S.
AU - Heiss, Christian
AU - Karthik, Chandra
AU - Contreras, Christopher J.
AU - Glushka, John
AU - Ishihara, Mayumi
AU - Azadi, Parastoo
AU - Hurley, Thomas D.
AU - Depaoli-Roach, Anna A.
AU - Roach, Peter J.
N1 - Funding Information:
Supported in part by National Institutes of Health (NIH) grants DK27221 and NS56454 (to P.J.R.), NIH/National Center for Research Resources grant P41 RR018502 to the Complex Carbohydrate Research Center, University of Georgia, and the American Heart Association (to V.S.T.). We thank Zhong-Yin Zhang, James Maller, and Nina Raben for comments regarding the manuscript.
PY - 2011/3/2
Y1 - 2011/3/2
N2 - Glycogen is a branched polymer of glucose that serves as an energy store. Phosphate, a trace constituent of glycogen, has profound effects on glycogen structure, and phosphate hyperaccumulation is linked to Lafora disease, a fatal progressive myoclonus epilepsy that can be caused by mutations of laforin, a glycogen phosphatase. However, little is known about the metabolism of glycogen phosphate. We demonstrate here that the biosynthetic enzyme glycogen synthase, which normally adds glucose residues to glycogen, is capable of incorporating the β-phosphate of its substrate UDP-glucose at a rate of one phosphate per approximately 10,000 glucoses, in what may be considered a catalytic error. We show that the phosphate in glycogen is present as C2 and C3 phosphomonoesters. Since hyperphosphorylation of glycogen causes Lafora disease, phosphate removal by laforin may thus be considered a repair or damage control mechanism.
AB - Glycogen is a branched polymer of glucose that serves as an energy store. Phosphate, a trace constituent of glycogen, has profound effects on glycogen structure, and phosphate hyperaccumulation is linked to Lafora disease, a fatal progressive myoclonus epilepsy that can be caused by mutations of laforin, a glycogen phosphatase. However, little is known about the metabolism of glycogen phosphate. We demonstrate here that the biosynthetic enzyme glycogen synthase, which normally adds glucose residues to glycogen, is capable of incorporating the β-phosphate of its substrate UDP-glucose at a rate of one phosphate per approximately 10,000 glucoses, in what may be considered a catalytic error. We show that the phosphate in glycogen is present as C2 and C3 phosphomonoesters. Since hyperphosphorylation of glycogen causes Lafora disease, phosphate removal by laforin may thus be considered a repair or damage control mechanism.
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U2 - 10.1016/j.cmet.2011.01.017
DO - 10.1016/j.cmet.2011.01.017
M3 - Article
C2 - 21356517
AN - SCOPUS:79952163604
SN - 1550-4131
VL - 13
SP - 274
EP - 282
JO - Cell Metabolism
JF - Cell Metabolism
IS - 3
ER -