The accepted name varies according to the source of the enzyme and the nature of its synthetic product (cf. EC 2.4.1.1, phosphorylase). Glycogen synthase from animal tissues is a complex of a catalytic subunit and the protein glycogenin. The enzyme requires glucosylated glycogenin as a primer; this is the reaction product of EC 2.4.1.186 (glycogenin glucosyltransferase). A similar enzyme utilizes ADP-glucose (EC 2.4.1.21, starch synthase).
glycogen synthase performs a stepwise SNi-like mechanism, involving the concerted departure of the leaving group and the attack of the incoming nucleophile, via ion-pair intermediate 1,5-anhydro-D-arabino-hex-1-enitol or its tautomeric form, 1,5-anhydro-D-fructose, bound at the catalytic site. Even in the absence of a glucosyl acceptor, glycogen synthase promotes the formation of the cationic intermediate, which, by eliminating the proton of the adjacent C2 carbon atom, yields 1,5-anhydro-D-arabino-hex-1-enitol, overview
The accepted name varies according to the source of the enzyme and the nature of its synthetic product (cf. EC 2.4.1.1, phosphorylase). Glycogen synthase from animal tissues is a complex of a catalytic subunit and the protein glycogenin. The enzyme requires glucosylated glycogenin as a primer; this is the reaction product of EC 2.4.1.186 (glycogenin glucosyltransferase). A similar enzyme utilizes ADP-glucose (EC 2.4.1.21, starch synthase).
enzyme polymerizes glucose residues to the outer chains of amylopectin. These chains subsequently are cleaved off amylopectin to generate mature amylose
transfers glucose to glycogen as well as to its phosphorylase limit dextrin, but not to its beta-amylase dextrin, glucose, maltose and maltotriose are not acceptors
glycogen synthase reacts with its glucosyl donor substrate, uridine 5'-diphosphoglucose to produce the scission of the covalent bond between the terminal phosphate oxygen of UDP and the sugar ring. UDP presence in the active site of the enzyme of a glucose-like derivative that lacks the exocyclic oxygen attached to the anomeric carbon
a point mutation in the UDP-glucose diphosphorylase gene results in decreases of UDP-glucose. Chronically low UDP-glucose levels in cells result in inactivation of glycogen synthase, owing to loss of the ability of glycogen synthase to bind UDP-glucose - non-substrate-dependent control of glycogen synthase
one mechanism by which peroxisome proliferator-activated receptor-alpha agonist treatment improves whole body insulin sensitivity is by increasing skeletal muscle GS total activity
one mechanism by which peroxisome proliferator-activated receptor-alpha agonist treatment improves whole body insulin sensitivity is by increasing skeletal muscle GS total activity
key enzyme in regulation of glycogen synthesis, controlled by multisite phosphorylation, phosphorylation of Ser640 by DYRK family protein kinases causes strong inactivation of glycogen synthase, functionally important site 3a in glycogen synthase by protein kinases from the DYRK family may be involved in a mechanism for the regulation of glycogen synthesis
a point mutation in the UDP-glucose diphosphorylase gene results in decreases of UDP-glucose. Chronically low UDP-glucose levels in cells result in inactivation of glycogen synthase, owing to loss of the ability of glycogen synthase to bind UDP-glucose - non-substrate-dependent control of glycogen synthase
one mechanism by which peroxisome proliferator-activated receptor-alpha agonist treatment improves whole body insulin sensitivity is by increasing skeletal muscle GS total activity
one mechanism by which peroxisome proliferator-activated receptor-alpha agonist treatment improves whole body insulin sensitivity is by increasing skeletal muscle GS total activity
key enzyme in regulation of glycogen synthesis, controlled by multisite phosphorylation, phosphorylation of Ser640 by DYRK family protein kinases causes strong inactivation of glycogen synthase, functionally important site 3a in glycogen synthase by protein kinases from the DYRK family may be involved in a mechanism for the regulation of glycogen synthesis
the eukaryotic enzyme is inhibited by protein kinase mediated phosphorylation, four arginine residues of a regulatory helix regulate the response to phosphorylation. When Thr668 is phosphorylated, Arg580 and Arg581 play a role in stabilizing the inhibited conformation by directly interacting with the phosphate group at or near the N-terminus of the regulatory helix, possibly near one of the sulfate binding sites in our basal state structure
D-glucose 6-phosphate binding structure, Arg580 forms an interaction with the 6-phosphate of D-glucose 6-phosphate, overview. The eukaryotic enzyme is activated by protein phosphatases and D-glucose 6-phosphate binding. The enzyme's response to D-glucose 6-phosphate is controlled by Arg583 and Arg587, while four additional arginine residues present within the same regulatory helix regulate the response to phosphorylation
stimulation of activity. In patients with type 2 diabetes a significant decrease in glycogen synthase activity is accompanied by the decrease in the effect of peptides, giving the following order of their efficiency: insulin = IGF-1> relaxin. In myometrium of pregnant women with gestational treated and untreated diabetes, glycogen synthase activity decreases, the effect of insulin is weaker, whereas the effects of relaxin and IGF-1increase thus giving the following order of their efficiency: relaxin > IGF-1 > insulin. Insulin therapy of type 1 diabetes incompletely restores sensitivity of the enzymes to the peptide actions
stimulation of activity. In patients with type 2 diabetes a significant decrease in glycogen synthase activity is accompanied by the decrease in the effect of peptides, giving the following order of their efficiency: insulin = IGF-1 > relaxin. In myometrium of pregnant women with gestational treated and untreated diabetes, glycogen synthase activity decreases, the effect of insulin is weaker, whereas the effects of relaxin and IGF-1 increase thus giving the following order of their efficiency: relaxin > IGF-1 > insulin. Insulin therapy of type 1 diabetes incompletely restores sensitivity of the enzymes to the peptide actions
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
synthase D, i.e. phosphorylated form, is glucose 6-phosphate dependent, synthase I, i.e. dephosphorylated form, is glucose 6-phosphate independent, interconversion of D and I forms and vice versa
stimulation of activity. In patients with type 1 diabetes glycogen synthase activity remains unchanged versus control, and insulin does not stimulate the enzyme activity. In patients with type 2 diabetes a significant decrease in glycogen synthase activity is accompanied by the decrease in the effect of peptides, giving the following order of their efficiency: insulin = IGF-1> relaxin. In myometrium of pregnant women with gestational treated and untreated diabetes, glycogen synthase activity decreases, the effect of insulin is weaker, whereas the effects of relaxin and IGF-1increase thus giving the following order of their efficiency: relaxin > IGF-1> insulin. Insulin therapy of type 1 diabetes incompletely restores sensitivity of the enzymes to the peptide actions
assay based on ESI-mass spectrometry enables detection of submicromolar quantities of substrate, thus requiring even lower concentrations of protein and is amenable to high throughput screening methods
synthetic peroxisome proliferator-activated receptor beta/delta, and gamma agonists markedly up-regulate Gys-2 mRNA and protein expression in mouse 3T3-L1 adipocytes
hypoxia activates glycogen synthase in fed rat myocardium through a combination of rapid glycogenolysis, elevated local glucose 6-phosphate content, and increased protein phosphatase 1 activity, and fasting attenuates this action independent of local glucose 6-phosphate content. Activation of glycogen synthase in myocardium induced by intermittent hypoxia is much lower in fasted than in fed rats
glycolytic glioma cells with active glycogen synthase are sensitive to phosphatase and tensin homolog (PTEN) and inhibitors of phosphatidylinositol-3 kinase and gluconeogenesis
in distal tubular cells, adiponectin through luminal ADIPOR1 activates AMPK, leading to the inhibition of glycogen synthase. During hyperglycemia, this regulation is altered, which may explain, at least in part, the accumulation of large glycogen deposits
glycolytic glioma cells with active glycogensynthase are sensitive to phosphatase and tensin homolog (PTEN) and inhibitors of phosphatidylinositol-3 kinase and gluconeogenesis
expression of Gys-2 is significantly reduced in adipose tissue of peroxisome proliferator-activated receptor alpha-/-, peroxisome proliferator-activated receptor beta/delta-/- and peroxisome proliferator-activated receptor gamma+/- mice
insulin receptor substrate (IRS) protein 1 knockdown reduces the glycogen synthase activity in parental HepG2 cells. It is upregulated in HepG2-CA-Akt/PKB cells
upon rapamycin treatment, the overexpression of constitutively active Akt-1 in Hep-G2 cells leads to an increase in the phosphorylation of Akt (Ser 473) and, an increase in the GS and PP-1 activities, in contrast to a decrease in Akt phosphorylation and GS and PP-1 activities in parental HepG2 cells
reduction in glucose production in primary hepatocytes by the overexpression of the mutant GYS2. The elevation of liver glycogen synthase activity in primary hepatocytes reduces glucose production by shunting gluconeogenic precursors into glycogen rather than by stimulating direct glucose incorporation into glycogen
basal glycogen synthase activity in muscle lacking rictor is increased to that of insulin-stimulated controls. A decrease in basal levels of phosphorylated glycogen synthase at a GSK-3/protein phosphatase 1 (glycogen-associated protein phosphatase 1)-regulated site in rictor knockout muscle is observed. This change in glycogen synthase phosphorylation is associated with an increase in the catalytic activity of glycogen-associated glycogen-associated protein phosphatase 1 but not increased GSK-3 inactivation
in low glycogen, basal and insulin-stimulated glycogen synthesis and glycogen synthase activation is higher and glycogen synthase phosphorylation (Ser645, Ser649, Ser653, Ser657) lower than in normal glycogen. Muscles with high glycogen show lower insulin-stimulated glycogen synthesis and glycogen synthase activation than normal glycogen despite similar dephosphorylation
sucrose feeding does not alter muscle glycogen concentration but provokes a small reduction in the glycogen synthase activity ratio (-/+ glucose-6-phosphate) in red but not in white gastrocnemius. Dexamethasone administration augments glycogen concentration and reduces glycogen synthase activity ratio in both muscle fiber types
existence of several glycogen metabolism regulatory mechanisms based on glycogen synthase intracellular compartmentalization. After exhausting exercise, epinephrine-induced protein kinase A activation leads to glycogen synthase site 1b phosphorylation targeting the enzyme to intramyofibrillar glycogen particles, which are preferentially used during muscle contraction. When phosphorylated at sites 2 + 2a, GS is preferentially associated with subsarcolemmal and intermyofibrillar glycogen particles. After overnight low muscle glycogen level and/or in response to exhausting exercise-induced glycogenolysis, glycogen synthase is associated with spherical structures at the I-band of sarcomeres
neither glycogen synthase activity nor glycogen synthase protein are present in the cytosolic fraction of subfractionated skeletal muscle obtained after an overnight fast or after 90 min of insulin infusion during a hyperinsulinemic euglycemic clamp in healthy or in insulin-resistant monkeys. Glycogen synthase activity, glycogen synthase protein, and glycogen are present in all other fractions. In vivo insulin regulation of skeletal muscle glycogen synthase activity does not involve changes in the subcellular localization of glycogen synthase. One mechanism by which peroxisome proliferator-activated receptor-alpha agonist treatment improves whole body insulin sensitivity is by increasing skeletal muscle GS total activity
neither glycogen synthase activity nor glycogen synthase protein are present in the cytosolic fraction of subfractionated skeletal muscle obtained after an overnight fast or after 90 min of insulin infusion during a hyperinsulinemic euglycemic clamp in healthy or in insulin-resistant monkeys. Glycogen synthase activity, glycogen synthase protein, and glycogen are present in all other fractions. In vivo insulin regulation of skeletal muscle glycogen synthase activity does not involve changes in the subcellular localization of glycogen synthase. One mechanism by which peroxisome proliferator-activated receptor-alpha agonist treatment improves whole body insulin sensitivity is by increasing skeletal muscle GS total activity
initial localization of glycogen synthase in a soluble pool plays an important role in glycogen synthesis, and that its sequestration in an insulin-resistant insoluble pool may explain in part the reduced glycogen synthesis caused by lipid oversupply
glycogen synthase homologues in bacteria and archaea lack regulation, while the eukaryotic enzymes are inhibited by protein kinase mediated phosphorylation and activated by protein phosphatases and D-glucose 6-phosphate binding
in the basal activity state and D-glucose 6-phosphate activated state, the enzyme is assembled into an unusual tetramer by an insertion unique to the eukaryotic enzymes, and this subunit interface is rearranged by the binding of D-glucose 6-phosphate, which frees the active site cleft and facilitates catalysis. Structure function in enzyme regulation, overview
glycogen synthase intrinsic activity is strongly dependent on glycogen levels. Regulation involves associated dephosphorylation at sites 2 + 2a, 3a, and 3a + 3b. There exist several glycogen metabolism regulatory mechanisms based on glycogen synthase intracellular compartmentalization. After exhausting exercise, epinephrine-induced protein kinase A activation leads to glycogen synthase site 1b phosphorylation targeting the enzyme to intramyofibrillar glycogen particles, which are preferentially used during muscle contraction. When phosphorylated at sites 2 + 2a, glycogen synthase is preferentially associated with subsarcolemmal and intermyofibrillar glycogen particles. After overnight low muscle glycogen level and/or in response to exhausting exercise-induced glycogenolysis, glycogen synthase is associated with spherical structures at the I-band of sarcomeres
in healthy subjects, adrenaline infusion increases blood glucose concentration by approximately 50%, but a hyperinsulinemic clamp normalizes blood glucose within 30 minutes. Insulin increases glycogen synthase fractional activity and decreases glycogen synthase Ser641 and Ser645,649,653,657 phosphorylation. In the presence of adrenaline, insulin does neither activate glycogen synthase nor dephosphorylate glycogen synthase Ser641. glycogen synthase Ser7 phosphorylation is not influenced by adrenaline. Adrenaline increases plasma lactate concentration, and muscle glycogen content is reduced in skeletal muscle the day after adrenaline infusion
a mutant strain defective in adenylyl cyclase activity accumulates, during vegetative growth, glycogen levels much higher than the wild type strain. The gsn transcript is not increased in this strain but the GSN protein is less phosphorylated in vitro, and therefore more active
glycogen synthase catalyzes the key step of glycogen synthesis and plays an important role in glycogen metabolism in liver and muscle, phosphorylation sites regulate the activity of the enzyme
glycogen synthase catalyzes the key step of glycogen synthesis and plays an important role in glycogen metabolism in liver and muscle, phosphorylation sites regulate the activity of the enzyme. Transcriptional regulation of GYS1 during myogenic differentiation in porcine satellite cells, overview. Effect of insulin is primarily mediated via posttranscriptional control the porcine glycogen synthase. Insulin promotes dephosphorylation of glycogen synthase in differentiated porcine satellite cells
glycogen synthase catalyzes the key step of glycogen synthesis and plays an important role in glycogen metabolism in liver and muscle, phosphorylation sites regulate the activity of the enzyme. Transcriptional regulation of GYS1 during myogenic differentiation in porcine satellite cells, overview. Effect of insulin is primarily mediated via posttranscriptional control the porcine glycogen synthase. Insulin promotes dephosphorylation of glycogen synthase in differentiated porcine satellite cells
glycogen synthase catalyzes the key step of glycogen synthesis and plays an important role in glycogen metabolism in liver and muscle, phosphorylation sites regulate the activity of the enzyme
homotrimeric protein. The contacts between subunits, which only involve the N-terminal domains, do not restrict the movements of the corresponding C-domains, likely required for catalysis
in healthy subjects, adrenaline infusion increases blood glucose concentration by approximately 50%, but a hyperinsulinemic clamp normalizes blood glucose within 30 minutes. Insulin increases glycogen synthase fractional activity and decreases glycogen synthase Ser641 and Ser645,649,653,657 phosphorylation. In the presence of adrenaline, insulin does neither activate glycogen synthase nor dephosphorylate glycogen synthase Ser641. Glycogen synthase Ser7 phosphorylation is not influenced by adrenaline. Adrenaline increases plasma lactate concentration, and muscle glycogen content is reduced in skeletal muscle the day after adrenaline infusion
phosphorylated by Ca2+-calmodulin dependent protein kinase in fast-twitch skeletal muscle. Phosphorylation does not affect glycogen synthase activity by itself, but it might be necessary for the modulation of glycogen synthase by other protein kinases
in low glycogen, basal and insulin-stimulated glycogen synthesis and glycogen synthase activation is higher and glycogen synthase phosphorylation (Ser645, Ser649, Ser653, Ser657) lower than in normal glycogen. Muscles with high glycogen show lower insulin-stimulated glycogen synthesis and glycogen synthase activation than normal glycogen despite similar dephosphorylation
in the absence of insulin, glycogen synthase Ser645, Ser649, Ser653, and Ser657 phosphorylation is similar in soleus muscles from control and dexamethasone-treated rats. In epitrochlearis, glycogen synthase phosphorylation is slightly elevated in muscles from dexamethasone-treated rats. Contraction decreases glycogen synthase Ser645, Ser649, Ser653, and Ser657 phosphorylation in soleus to a similar low level in muscles from control and dexamethasone-treated rats. In epitrochlearis muscles, contraction also decreases glycogen synthase phosphorylation to a low level in muscles from control and dexamethasone-treated rats. In soleus and epitrochlearis muscles, the combination of contraction and insulin does not decrease glycogen synthase phosphorylation more than contraction alone
the eukaryotic enzymes are inhibited by protein kinase mediated phosphorylation and activated by protein phosphatases and glucose-6-phosphate binding, regulation, overview
regulatory sites of GYS1 that undergo reversible phosphorylation are identified: two of them, sites 2 and 2a, are located near the N-terminus, while the remaining seven sites, 3a, 3b, 3c, 4, 5, 1a, and 1b, are found within the C-terminus. Insulin promotes dephosphorylation of glycogen synthase in differentiated porcine satellite cells
regulatory sites of GYS2 that undergo reversible phosphorylation are identified: two of them, sites 2 and 2a, are located near the N-terminus, while the remaining seven sites, 3a, 3b, 3c, 4, and 5 are found within the C-terminus, GYS2 does not contain sites 1a and 1b
regulatory sites of GYS1 that undergo reversible phosphorylation are identified: two of them, sites 2 and 2a, are located near the N-terminus, while the remaining seven sites, 3a, 3b, 3c, 4, 5, 1a, and 1b, are found within the C-terminus. Insulin promotes dephosphorylation of glycogen synthase in differentiated porcine satellite cells
regulatory sites of GYS2 that undergo reversible phosphorylation are identified: two of them, sites 2 and 2a, are located near the N-terminus, while the remaining seven sites, 3a, 3b, 3c, 4, and 5 are found within the C-terminus, GYS2 does not contain sites 1a and 1b
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
catalytic domain bound to ADP and inhibitor acarbose, hanging drop vapor diffusion method, using 40 mM citric acid, 60 mM Bis-Tris propane, pH 6.4 and 20% (w/v) PEG 3350
crystals from the protein and from its selenomethionyl variant are grown in 100 mM sodium citrate pH 5.6 containing 20% PEG and 20% dioxane by hanging drop vapour-diffusion method at 20°C. Crystals grow in thin needles, diffract to 3.5 A resolution and belong to space group C2, with unit-cell parameters a = 202 A, b = 73 A, c = 149 A, beta = 131°
purified recombinant enzyme in complex with UDP-Glc, sitting drop vapor diffusion method, 0.002 ml of 5 mg/ml protein in 50-mM Tris-HCl, pH 7.4, with 10 mM UDP-Glc is mixed with 0.002 ml reservoir solution containing 0.1-M sodium citrate, pH 4.0, and 20-28% 2-methyl-2,4-pentanediol, 2 months, 20°C, X-ray diffraction structure determination and analysis at 2.5 A resolution, molecular replacement
purified recombinant His-tagged enzyme, basal state and glucose-6-phosphate activated state Gsy2p, X-ray diffraction structure determination and analysis at 3.0 A and 2.4 A, respectively, modeling
mutation identified in a patient with glycogen storage disease type 0, together with frameshift mutation 966_967delGA/insC introducing a stop codon 21 amino acids downstream from the site of the mutation and leading to loss of 51% of the C-terminal portion of the protein. Patient is heterozygous for the mutations and presents with fasting hypoglycemia and postprandial hyperglycemia
phosphorylation mutant, large increase in the activity ratio both in soluble and insoluble fraction. Enzyme is almost fully active and able to induce glycogen deposition in primary hepatocytes incubated in the absence of glucose and in FTO2B cells, a cell line that does not normallysynthesize glycogen. Mutation is also sufficient to trigger the aggregation and translocation of liver glycogen synthase from the cytoplasm to the hepatocyte cell cortex in the absence of glucose
phosphorylation and active site mutant. Translocation of liver glycogen synthase from the cytoplasm to the hepatocyte cell cortex in the absence of glucose is not observed
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme. The triple mutant enzyme is resistant to inhibition by Pho85p/Pcl10p phosphorylation
identification of homozygous two base pair deletion in exon 2, c.162-163delAG resulting in muscle-specific glycogen synthase deficiency. Mutation is predicted to result in a protein frameshift that alters the amino acid sequence after the mutation and terminates prematurely. Patient presents with abnormal mitochondrial ultrastructure and pre-ragged red fibres, predominance of type I oxidative fibres in the muscle and depletion of glycogen stores
identification of homozygous two base pair deletion in exon 2, c.162-163delAG resulting in muscle-specific glycogen synthase deficiency. Mutation is predicted to result in a protein frameshift that alters the amino acid sequence after the mutation and terminates prematurely. Patient presents with abnormal mitochondrial ultrastructure and pre-ragged red fibres, predominance of type I oxidative fibres in the muscle and depletion of glycogen stores
generation of a wild-type 640 truncation mutant with increased activity compared to the wild-type, and of point mutation variants with nonphospho- and phospho-peptides ligated, which alters the mutant activities, overview
the COOH-terminal fragment of glycogenin can be used as an effective high affinity reagent for the purification of glycogen synthase from skeletal muscle and liver
gene GYS1, in silico cloning, DNA and amino acid sequence determination and analysis, promoter determination and analysis, quantitative real-time RT-PCR tissue expression analysis
gene GYS2, in silico cloning, DNA and amino acid sequence determination and analysis, promoter determination and analysis, quantitative real-time RT-PCR tissue expression analysis
heat-shock down-regulates gsn gene transcription in wild-type as well as in mutants deficient in adenylyl cyclase activity and a temperature-sensitive mutant defective in the regulatory subunit of protein kinase A
calorie restriciton does not alter glycogen synthase or glycogen phosphatase activity/protein levels in young rats. Calorie restriction hinders age-related decreases in glycogen synthase activity/protein, unrelated to glycogen synthase mRNA levels, and glycogen synthase inactivation-phosphorylation
glycogen synthase activity correlates inversely with phosphorylation of glycogen synthase sites 2 + 2a and 3a. Insulin significantly decreases 2 + 2a phosphorylation in lean subjects only and induces a larger dephosphorylation at site 3 in lean compared with obese subjects. The exaggerated insulin resistance in type 2 diabetes mellitus compared with obese subjects is not reflected by differences in site 3 phosphorylation but is accompanied by a significantly higher site 1b phosphorylation during insulin stimulation. Hyperphosphorylation of another Ca2/calmodulin-dependent kinase-II target, phospholamban-Thr17, is also evident in type 2 diabetes mellitus. Dephosphorylation of glycogen synthase by phosphatase treatment fully restores glycogen synthase activity in all groups
in patients with polycystic ovary syndrome, reduced insulin-mediated glucose disposal is associated with a lower insulin-stimulated glycogen synthase activity, explained by absent insulin-mediated dephosphorylation of glycogen synthase at the NH2-terminal sites 2 + 2a, whereas dephosphorylation at the COOH-terminal sites 3a + 3b is intact in polycystic ovary syndrome subjects. Insulin activation of glycogen synthase is dependent on dephosphorylation of sites 3a + 3b in women with polycystic ovary syndrome. No significant abnormalities in glycogen synthaseK-3 or -3 are found. Pioglitazone treatment improves insulin-stimulated glucose metabolism and glycogen synthase activity in polycystic ovary syndrome and restores the ability of insulin to dephosphorylate glycogen synthase at sites 2 and 2a
insulin, insiulin-like growth factor 1 and relaxin stimulate the enzymatic activity. In patients with type 1 diabetes glycogen synthase activity remains unchanged versus control, and insulin does not stimulate the enzyme activity. In patients with type 2 diabetes a significant decrease in glycogen synthase activity is accompanied by the decrease in the effect of peptides, giving the following order of their efficiency: insulin = IGF-1 > relaxin. In myometrium of pregnant women with gestational treated and untreated diabetes, glycogen synthase activity decreases, the effect of insulin is weaker, whereas the effects of relaxin and IGF-1 increase thus giving the following order of their efficiency: relaxin > IGF-1 > insulin. Insulin therapy of type 1 diabetes incompletely restores sensitivity of the enzymes to the peptide actions
mutation R243X has been identified in a patient with glycogen storage disease type 0, together with frameshift mutation 966_967delGA/insC introducing a stop codon 21 amino acids downstream from the site of the mutation and leading to loss of 51% of the C-terminal portion of the protein. Patient is heterozygous for the mutations and presents with fasting hypoglycemia and postprandial hyperglycemia
old compared to young rats maintained ad libitum on a standard diet have reduced glycogen synthase activity, lower muscle glycogen synthase protein levels, increased phosphorylation of glycogen synthase at site 3a with less activation in soleus muscle. Age-associated impairments in glycogen synthase protein and activation-phosphorylation are also shown in tibialis anterior muscle. There is an age-associated reduction in glycogen phosphorylase activity level in soleus, while brain/muscle isoforms of glycogen phosphorylase protein levels are higher. Calorie restriciton does not alter glycogen synthase or glycogen phosphatase activity/protein levels in young rats. Calorie restriction hinders age-related decreases in glycogen synthase activity/protein, unrelated to glycogen synthase mRNA levels, and glycogen synthase inactivation-phosphorylation
patient with muscle-specific glycogen synthase deficiency due to homozygous two base pair deletion in exon 2, c.162-163delAG. Mutation is predicted to result in a protein frameshift that alters the amino acid sequence after the mutation and terminates prematurely. Patient presents with abnormal mitochondrial ultrastructure and pre-ragged red fibres, predominance of type I oxidative fibres in the muscle and depletion of glycogen stores