Enzymes Aren't Perfect

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Science  08 Apr 2011:
Vol. 332, Issue 6026, pp. 150
DOI: 10.1126/science.332.6026.150-a

Cells have efficient quality-control systems to detect and repair errors in polymerization of DNA or RNA. Tagliabracci et al. reveal the biological effects of errors by another polymerase, glycogen synthase, which creates glycogen—branched chains of glucose that serve as an important energy store in cells. About 1 in 1000 of the glucose residues in normal glycogen contain covalently linked phosphate. The authors found that the major enzymatic activity from mouse muscle catalyzing such incorporation of phosphate was in fact glycogen synthase. Although the incorporated phosphate may serve a useful function, current evidence indicates it is probably a mistake. A phosphatase that removes phosphate from glycogen is known as laforin because mutations in the enzyme are associated with Lafora disease, a deadly human disease that causes neurodegeneration and epilepsy. The disease appears to result from insolubility of excessively phosphorylated glycogen. Thus, laforin is likely required to prevent deleterious effects of catalytic errors made by glycogen synthase.

Cell Metab. 13, 274 (2011).

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