| Dual regulation of muscle glycogen synthase during exercise by activation and compartmentalization. | |
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MedLine Citation:
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PMID: 19339242 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glycogen synthase (GS) is considered the rate-limiting enzyme in glycogenesis but still today there is a lack of understanding on its regulation. We have previously shown phosphorylation-dependent GS intracellular redistribution at the start of glycogen re-synthesis in rabbit skeletal muscle (Prats, C., Cadefau, J. A., Cussó, R., Qvortrup, K., Nielsen, J. N., Wojtaszewki, J. F., Wojtaszewki, J. F., Hardie, D. G., Stewart, G., Hansen, B. F., and Ploug, T. (2005) J. Biol. Chem. 280, 23165-23172). In the present study we investigate the regulation of human muscle GS activity by glycogen, exercise, and insulin. Using immunocytochemistry we investigate the existence and relevance of GS intracellular compartmentalization during exercise and during glycogen re-synthesis. The results show that GS intrinsic activity is strongly dependent on glycogen levels and that such regulation involves associated dephosphorylation at sites 2+2a, 3a, and 3a + 3b. Furthermore, we report the existence of several glycogen metabolism regulatory mechanisms based on GS intracellular compartmentalization. After exhausting exercise, epinephrine-induced protein kinase A activation leads to GS site 1b phosphorylation targeting the enzyme to intramyofibrillar glycogen particles, which are preferentially used during muscle contraction. On the other hand, when phosphorylated at sites 2+2a, GS is preferentially associated with subsarcolemmal and intermyofibrillar glycogen particles. Finally, we verify the existence in human vastus lateralis muscle of the previously reported mechanism of glycogen metabolism regulation in rabbit tibialis anterior muscle. After overnight low muscle glycogen level and/or in response to exhausting exercise-induced glycogenolysis, GS is associated with spherical structures at the I-band of sarcomeres. |
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Authors:
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Clara Prats; Jørn W Helge; Pernille Nordby; Klaus Qvortrup; Thorkil Ploug; Flemming Dela; Jørgen F P Wojtaszewski |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-04-01 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 284 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-06-01 Completed Date: 2009-07-13 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 15692-700 Citation Subset: IM |
Affiliation:
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Copenhagen Muscle Research Center, Center for Healthy Ageing, Department of Biomedical Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark. cprats@mfi.ku.dk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Amino Acid Sequence Biopsy Blood Glucose / metabolism Enzyme Activation Epinephrine / blood Glycogen / metabolism Glycogen Synthase / chemistry, metabolism* Humans Insulin / blood Kinetics Leg Muscle Proteins / isolation & purification, metabolism Muscle, Skeletal / enzymology, physiology* Peptide Fragments / chemistry Phosphorylation Reference Values Sarcomeres / enzymology* |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Muscle Proteins; 0/Peptide Fragments; 11061-68-0/Insulin; 51-43-4/Epinephrine; 9005-79-2/Glycogen; EC 2.4.1.11/Glycogen Synthase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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