Lack of glycogenin causes glycogen accumulation and muscle function impairment

Glycogenin is considered essential for glycogen synthesis, as it acts as a primer for the initiation of the polysaccharide chain. Against expectations, glycogenin-deficient mice (Gyg KO) accumulate high amounts of glycogen in striated muscle. Furthermore, this glycogen contains no covalently bound p...

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Detalles Bibliográficos
Autores: Testoni, Giorgia, Duran, Jordi, García-Rocha, Mar, Vilaplana, Francisco, Serrano, Antonio L., Sebastián, David, López Soldado, Iliana, Sullivan, Mitchell A., Slebe Concha, Juan Felipe, 1981-, Vilaseca, Marta, Muñoz Cánoves, Pura, 1962-, Guinovart, Joan J. (Joan Josep), 1947-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/36843
Acceso en línea:http://hdl.handle.net/10230/36843
http://dx.doi.org/10.1016/j.cmet.2017.06.008
Access Level:acceso abierto
Palabra clave:Glycogenin
Glycogen
GSD XV
Glycogen storage disease XV
Glycogenosis
Exercise
Muscle performance
Priming protein
Oxidative metabolism
Mitochondrial respiration
Descripción
Sumario:Glycogenin is considered essential for glycogen synthesis, as it acts as a primer for the initiation of the polysaccharide chain. Against expectations, glycogenin-deficient mice (Gyg KO) accumulate high amounts of glycogen in striated muscle. Furthermore, this glycogen contains no covalently bound protein, thereby demonstrating that a protein primer is not strictly necessary for the synthesis of the polysaccharide in vivo. Strikingly, in spite of the higher glycogen content, Gyg KO mice showed lower resting energy expenditure and less resistance than control animals when subjected to endurance exercise. These observations can be attributed to a switch of oxidative myofibers toward glycolytic metabolism. Mice overexpressing glycogen synthase in the muscle showed similar alterations, thus indicating that this switch is caused by the excess of glycogen. These results may explain the muscular defects of GSD XV patients, who lack glycogenin-1 and show high glycogen accumulation in muscle.