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Regulation of glycogen synthase from mammalian skeletal muscle. A unifying view of allosteric and covalent regulation.
MedLine Citation:
PMID:  23134486     Owner:  NLM     Status:  Publisher    
It is widely accepted that insufficient insulin-stimulated activation of muscle glycogen synthesis is one of the major components of non-insulin-dependent (type 2) diabetes mellitus. Glycogen synthase, a key enzyme in muscle glycogen synthesis, is extensively regulated, both allosterically (by glucose-6-phosphate, ATP, and others) and covalently (by phosphorylation). Although glycogen synthase has been a topic of intense study for more than 50 years, its kinetic characterization has been confounded by its large number of phosphorylation states. Questions remain regarding the function of glycogen synthase regulation and the relative importance of allosteric and covalent modification in fulfilling this function. In this review we consider both the earlier kinetic studies and the more recent site-directed mutagenesis and crystal structure studies in a detailed qualitative discussion of the effects of regulation on the kinetics of glycogen synthase. We propose that both allosteric and covalent modification of glycogen synthase can be described by a Monod-Wyman-Changeux model in terms of apparent changes to L, the equilibrium constant for transition between the T and R conformers. Since, with the exception of L, all parameters of this model are independent of the glycogen synthase phosphorylation state, the need to determine kinetic parameters for all the possible states is eliminated; only the relationship between a particular state and L must be established. We conclude by suggesting that renewed efforts to characterize the relationship between phosphorylation and the kinetics of glycogen synthase are essential in order to obtain a better quantitative understanding of the function of glycogen synthesis regulation. The model we propose could prove useful in this regard. © 2012 The Authors Journal compilation © 2012 FEBS.
Daniel C Palm; Johann M Rohwer; Jan-Hendrik S Hofmeyr
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  The FEBS journal     Volume:  -     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Journal compilation © 2012 FEBS.
Triple-J Group for Molecular Cell Physiology, Department of Biochemistry, Stellenbosch University, Private Bag X1, 7602, Matieland, South Africa.
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