Glycogen metabolism and signal transduction in mammals and yeast

Roach, Peter J.; Cao, Youjia; Corbett, Cheryl A.; DePaoli‐Roach, Anna A.; Farkas, Illés J.; Fiol, Carol J.; Flotow, Horst; Graves, Paul R.; Hardy, Thomas; Hrubey, Todd Warren; Viskupic, E; Zhang, W.

doi:10.1016/0065-2571(91)90011-a

Cited by 20 publications

(11 citation statements)

References 83 publications

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“…PKA phosphorylates glycogen phosphorylase kinase, which, in turn, phosphorylates GP and converts it from the inactive b form to the active a form (Johnson, 1992). Concurrently, PKA also phosphorylates and inactivates glycogen synthase (GS), shutting off glycogen synthesis (glycogenesis) (Roach et al, 1991). Thus, glycogenolysis and glycogenesis are prevented from directly competing with one another.…”

Section: Introductionmentioning

confidence: 99%

Glycogen synthase kinase-3: cryoprotection and glycogen metabolism in the freeze-tolerant wood frog

Dieni

Bouffard

Storey

2012

Journal of Experimental Biology

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SUMMARYThe terrestrial anuran Rana sylvatica tolerates extended periods of whole-body freezing during the winter. Freezing survival is facilitated by extensive glycogen hydrolysis and distribution of high concentrations of the cryoprotectant glucose into blood and all tissues. As glycogenesis is both an energy-expensive process and counter-productive to maintaining sustained high cryoprotectant levels, we proposed that glycogen synthase kinase-3 (GSK-3) would be activated when wood frogs froze and would phosphorylate its downstream substrates to inactivate glycogen synthesis. Western blot analysis determined that the amount of phosphorylated (inactive) GSK-3 decreased in all five tissues tested in 24h frozen frogs compared with unfrozen controls. Total GSK-3 protein levels did not change, with the exception of heart GSK-3, indicating that post-translational modification was the primary regulatory mechanism for this kinase. Kinetic properties of skeletal muscle GSK-3 from control and frozen frogs displayed differential responses to a temperature change (22 versus 4°C) and high glucose. For example, when assayed at 4°C, the K m for the GSK-3 substrate peptide was ~44% lower for frozen frogs than the corresponding value in control frogs, indicating greater GSK-3 affinity for its substrates in the frozen state. This indicates that at temperatures similar to the environment encountered by frogs, GSK-3 in frozen frogs will phosphorylate its downstream targets more readily than in unfrozen controls. GSK-3 from skeletal muscle of control frogs was also allosterically regulated. AMP and phosphoenolpyruvate activated GSK-3 whereas inhibitors included glucose, glucose 6-phosphate, pyruvate, ATP, glutamate, glutamine, glycerol, NH 4 Cl, NaCl and KCl. The combination of phosphorylation and allosteric control argues for a regulatory role of GSK-3 in inactivating glycogenesis to preserve high glucose cryoprotectant levels throughout each freezing bout.

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Section: Introductionmentioning

confidence: 99%

Glycogen synthase kinase-3: cryoprotection and glycogen metabolism in the freeze-tolerant wood frog

Dieni

Bouffard

Storey

2012

Journal of Experimental Biology

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“…Almost all the studies of muscle and liver GS have focused on the covalent and allosteric regulation by hormonal and metabolic stimuli (15)(16)(17), and few attempts have been made to elucidate the catalytic mechanism (18). The aim of this study was to identify conserved regions and putative catalytic residues through the comparison of the amino acid sequences of mammalian GSs with those of other known retaining glycosyltransferases.…”

mentioning

confidence: 99%

Identification of Two Essential Glutamic Acid Residues in Glycogen Synthase

Cid¹,

Gomis²,

Geremia³

et al. 2000

Journal of Biological Chemistry

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The detailed catalytic mechanism by which glycosyltransferases catalyze the transfer of a glycosyl residue from a donor sugar to an acceptor is not known. Through the multiple alignment of all known eukaryotic glycogen synthases we have found an invariant 17-amino acid stretch enclosed within the most conserved region of the members of this family. This peptide includes an E-X 7 -E motif, which is highly conserved in four families of retaining glycosyltransferases. Site-directed mutagenesis was performed in human muscle glycogen synthase to analyze the roles of the two conserved Glu residues (Glu-510 and Glu-518) of the motif. Proteins were transiently expressed in COS-1 cells as fusions to green fluorescence protein. The E510A and E518A mutant proteins retained the ability to translocate from the nucleus to the cytosol in response to glucose and to bind to intracellular glycogen. Although the E518A variant had approximately 6% of the catalytic activity shown by the green fluorescence protein-human muscle glycogen synthase fusion protein, the E510A mutation inactivated the enzyme. These results led us to conclude that the E-X 7 -E motif is part of the active site of eukaryotic glycogen synthases and that both conserved Glu residues are involved in catalysis. We propose that Glu-510 may function as the nucleophile and Glu-518 as the general acid/base catalyst.Glycosyltransferases and glycosidases catalyze the transfer of glycosyl residues from a donor sugar to an acceptor. The acceptor in glycosidases is water, the end result being hydrolysis of the glycoconjugate. For transferases the acceptor molecule is in most cases a growing carbohydrate chain, but it can also be a protein, a lipid, or a range of other compounds such as steroids, bilirubin, flavonones, carotenoids, etc

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“…Este estado de fosforilación puede ser afectado por varias quinasas y fosfatasas, entre las cuales están la quinasa de la caseína I y II , la quinasa dependiente del cAMP, la glucógeno sintasa quinasa y la protein-fosfatasa-1 (Roach et al 1991). Estas enzimas son a su vez reguladas por fosforilación (Roach et al 1991, Woodgett 1994) y son probablemente elementos corriente abajo de vías de señales de transducción iniciadas por la insulina, glucagón, hormonas adrenérgicas y otros factores. La Laforina por ser una fosfatasa tirosínica proteica podría estar involucrada en la fosforegulación de las anteriores u otras enzimas que controlan a la glucógeno sintasa.…”

Section: Patologíaunclassified

“…La Laforina por ser una fosfatasa tirosínica proteica podría estar involucrada en la fosforegulación de las anteriores u otras enzimas que controlan a la glucógeno sintasa. No se espera que la Laforina actúe directamente sobre la glucógeno sintasa porque la desfosforilación inhibe a esta última (Roach et al 1991).…”

Section: Patologíaunclassified

Epilepsia mioclónica progresiva tipo Lafora y los casos diagnosticados en Costa Rica

Solís

2014

RBT

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Glycogen metabolism and signal transduction in mammals and yeast

Cited by 20 publications

References 83 publications

Glycogen synthase kinase-3: cryoprotection and glycogen metabolism in the freeze-tolerant wood frog

Glycogen synthase kinase-3: cryoprotection and glycogen metabolism in the freeze-tolerant wood frog

Identification of Two Essential Glutamic Acid Residues in Glycogen Synthase

Epilepsia mioclónica progresiva tipo Lafora y los casos diagnosticados en Costa Rica

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