Phosphate Incorporation During Glycogen Synthesis and Lafora Disease

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2011 Mar 2

PMID 21356517

Citations 53

Authors

Vincent S Tagliabracci

Christian Heiss

Chandra Karthik

Christopher J Contreras

John Glushka

Mayumi Ishihara

Parastoo Azadi

Thomas D Hurley

Anna A DePaoli-Roach

Peter J Roach

Affiliations

Soon will be listed here.

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.

Citing Articles

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