title: Phosphate incorporation during glycogen synthesis and Lafora disease.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Vincent S
authors.initials: VS
authors.lastname: Tagliabracci
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Chandra
authors.initials: C
authors.lastname: Karthik
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Contreras
authors.forename: John
authors.initials: J
authors.lastname: Glushka
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishihara
authors.forename: Parastoo
authors.initials: P
authors.lastname: Azadi
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Hurley
authors.forename: Anna A
authors.initials: AA
authors.lastname: DePaoli-Roach
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Roach
mesh_terms: D000818:Animals; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism; D020192:Lafora Disease / Q000201:enzymology; D010710:Phosphates / Q000378:metabolism*; D010766:Phosphorylation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism*; D011817:Rabbits; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
chemical_list: D010710:Phosphates; D006003:Glycogen; D006006:Glycogen Synthase; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D014532:Uridine Diphosphate Glucose