Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism

2015 ◽  
Vol 13 (26) ◽  
pp. 7282-7288 ◽  
Author(s):  
Mireia Díaz-Lobo ◽  
Jaume Garcia-Amorós ◽  
Ignacio Fita ◽  
Dolores Velasco ◽  
Joan J. Guinovart ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Selective Inhibitor ◽  
Key Enzymes

An azobenzene glucoside was synthesized and was shown to be an excellent selective inhibitor of Escherichia coli glycogen synthase in its photogenerated (Z)-form, which structurally resembles the three terminal glucoses of a glycogen branch.

scholarly journals Correction: Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism

2015 ◽  
Vol 13 (39) ◽  
pp. 10072-10072 ◽  
Author(s):  
Mireia Díaz-Lobo ◽  
Jaume Garcia-Amorós ◽  
Ignacio Fita ◽  
Dolores Velasco ◽  
Joan J. Guinovart ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Key Enzymes

Correction for ‘Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism’ by Mireia Díaz-Lobo, et al., Org. Biomol. Chem., 2015, 13, 7282–7288.

Ontogeny of some enzymes of glycogen metabolism in rabbit fetal heart, lungs, and liver

1983 ◽  
Vol 61 (4) ◽  
pp. 191-197 ◽  
Author(s):  
Bhagu R. Bhavnani
Keyword(s):  
Glycogen Phosphorylase ◽  
Fetal Heart ◽  
Glycogen Synthase ◽  
Fetal Liver ◽  
Active Form ◽  
Fetal Lung ◽  
Glycogen Metabolism ◽  
Near Term ◽  
Surfactant Phospholipids ◽  
Total Tissue

Optimum conditions were established for the assay of glycogen, glycogen synthase, glycogen phosphorylase, phosphoglucomutase, and glucose-6-phosphatase in rabbit fetal heart, lung, and liver. Using these methods, the pattern of appearance of glycogen and the above four enzymes was established from day 18 of gestation to day 8 after birth. The results indicate that total tissue glycogen reaches maximum levels between days 22 and 24 in the heart, days 24 and 26 in the lung, and days 30 and 31 in the liver. In all three tissues, the rapid rise or depletion of glycogen is coincident with a corresponding increase in glycogen synthase and glycogen phosphorylase activities. However, substantial amounts of glycogen synthase are present both prior to and after the accumulation of glycogen. Similarly, considerable amounts of glycogen phosphorylase are present early in gestation, yet deposition of glycogen occurs. Both the I and D forms of glycogen synthase are present in the three tissues, the major being the physiologically inactive D form. Similarly both the a and b forms of glycogen phosphorylase are present, with the a form (active form) making up about 30–60% of the total phosphorylase activity. Glucose-6-phosphatase was absent in fetal heart and lung throughout the period of gestation investigated. Low levels of this enzyme were detectable in fetal liver near term. The phosphoglucomutase activity increased progressively from day 22 of gestation in all three tissues and continues to increase after birth. The disappearance of fetal lung glycogen occurs between days 27 and 28 at a time when surfactant phospholipids first appear. These findings indicate that the breakdown of glycogen is providing the fetal lung cells with energy necessary for surfactant phospholipid biosynthesis.

scholarly journals Regulation of glycogen metabolism in cultured human muscles by the glycogen phosphorylase inhibitor CP-91149

2004 ◽  
Vol 378 (3) ◽  
pp. 1073-1077 ◽  
Author(s):  
Carlos LERÍN ◽  
Eulàlia MONTELL ◽  
Teresa NOLASCO ◽  
Mar GARCÍA-ROCHA ◽  
Joan J. GUINOVART ◽  
...  
Keyword(s):  
Muscle Glycogen ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Muscle Cells ◽  
Glycogen Metabolism ◽  
Human Muscle ◽  
Insulin Dependent Diabetes ◽  
Type Ii ◽  
Insulin Dependent ◽  
Human Muscle Cells

Pharmacological inhibition of liver GP (glycogen phosphorylase), which is currently being studied as a treatment for Type II (non-insulin-dependent) diabetes, may affect muscle glycogen metabolism. In the present study, we analysed the effects of the GP inhibitor CP-91149 on non-engineered or GP-overexpressing cultured human muscle cells. We found that CP-91149 treatment decreased muscle GP activity by (1) converting the phosphorylated AMP-independent a form into the dephosphorylated AMP-dependent b form and (2) inhibiting GP a activity and AMP-mediated GP b activation. Dephosphorylation of GP was exerted, irrespective of incubation of the cells with glucose, whereas inhibition of its activity was synergic with glucose. As expected, CP-91149 impaired the glycogenolysis induced by glucose deprivation. CP-91149 also promoted the dephosphorylation and activation of GS (glycogen synthase) in non-engineered or GP-overexpressing cultured human muscle cells, but exclusively in glucose-deprived cells. However, this inhibitor did not activate GS in glucose-deprived but glycogen-replete cells overexpressing PTG (protein targeting to glycogen), thus suggesting that glycogen inhibits the CP-91149-mediated activation of GS. Consistently, CP-91149 promoted glycogen resynthesis, but not its overaccumulation. Hence, treatment with CP-91149 impairs muscle glycogen breakdown, but enhances its recovery, which may be useful for the treatment of Type II (insulin-dependent) diabetes.

Electrical stimulation of the liver cell: activation of glycogenolysis

1981 ◽  
Vol 240 (3) ◽  
pp. E226-E232
Author(s):  
K. A. Freude ◽  
L. S. Sandler ◽  
F. J. Zieve
Keyword(s):  
Electrical Stimulation ◽  
Metabolic Regulation ◽  
Glycogen Phosphorylase ◽  
Cell Activation ◽  
Current Flow ◽  
Glycogen Synthase ◽  
Rat Hepatocytes ◽  
Glycogen Metabolism ◽  
Liver Glycogen

To examine the role of ionic factors in the regulation of glycogen metabolism, we examined the effects of electrical stimulation on liver glycogen cycle enzymes. Passage of electric current through a suspension of rat hepatocytes caused the conversion of glycogen phosphorylase to its active (a) form and the simultaneous conversion of glycogen synthase to its inactive (D) form. The rise in phosphorylase a activity was dependent on the magnitude of current flow, was detectable after 5 s of current flow, and was rapidly reversible on cessation of stimulation. The activation of phosphorylase by shocking was completely eliminated by depletion of cellular Ca2+ and was restored by readdition of Ca2+. Cyclic AMP and cyclic GMP levels were unaffected by shocking. It is concluded that shocking, in the absence of any hormone or exogenous chemical, causes an increase in cytosol Ca2+, which in turn leads to activation of phosphorylase and inactivation of synthase. Electrical stimulation may serve as a model system for studying the role of ions in metabolic regulation.

scholarly journals Dynamic Variations in Brain Glycogen are Involved in Modulating Isoflurane Anesthesia in Mice

2020 ◽  
Vol 36 (12) ◽  
pp. 1513-1523
Author(s):  
Ze Fan ◽  
Zhihao Zhang ◽  
Shiyi Zhao ◽  
Yuanyuan Zhu ◽  
Dong Guo ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Brain Regions ◽  
Brain Glycogen ◽  
Dynamic Variations ◽  
Term Delivery ◽  
Lower Ratio ◽  
Increased Activity

Abstract General anesthesia severely affects the metabolites in the brain. Glycogen, principally stored in astrocytes and providing the short-term delivery of substrates to neurons, has been implicated as an affected molecule. However, whether glycogen plays a pivotal role in modulating anesthesia–arousal remains unclear. Here, we demonstrated that isoflurane-anesthetized mice exhibited dynamic changes in the glycogen levels in various brain regions. Glycogen synthase (GS) and glycogen phosphorylase (GP), key enzymes of glycogen metabolism, showed increased activity after isoflurane exposure. Upon blocking glycogenolysis with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), a GP antagonist, we found a prolonged time of emergence from anesthesia and an enhanced δ frequency in the EEG (electroencephalogram). In addition, augmented expression of glycogenolysis genes in glycogen phosphorylase, brain (Pygb) knock-in (PygbH11/H11) mice resulted in delayed induction of anesthesia, a shortened emergence time, and a lower ratio of EEG-δ. Our findings revealed a role of brain glycogen in regulating anesthesia–arousal, providing a potential target for modulating anesthesia.

Effects of crustacean hyperglycemic hormone (CHH) RNA interference on regulation of glucose metabolism in Litopenaeus vannamei after ammonia-N exposure

2021 ◽  
pp. 1-40
Author(s):  
Xin Zhang ◽  
Luqing Pan ◽  
Ruixue Tong ◽  
Yufen Li ◽  
Lingjun Si ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Litopenaeus Vannamei ◽  
Glycogen Phosphorylase ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Crustacean Hyperglycemic Hormone ◽  
Hyperglycemic Hormone ◽  
Rate Limiting ◽  
Creb Pathway

Abstract To unveil the adaptation of Litopenaeus vannamei to elevated ambient ammonia-N, crustacean hyperglycemic hormone (CHH) was knocked down to investigate its function in glucose metabolism pathway under ammonia-N exposure. When CHH was silenced, haemolymph glucose increased significantly during 3-6 h, decreased significantly during 12-48 h, and recovered to the control groups’ level at 72 h. After CHH knockdown, DA contents reduced significantly during 3-24 h, which recovered after 48 h. Besides, the expressions of GC and DA1R in the hepatopancreas decreased significantly, while DA4R increased significantly. Correspondingly, the contents of cAMP, cGMP and DAG and the expressions of PKA, PKG, AMPKα and AMPKγ were significantly downregulated, while the levels of PKC and AMPKβ were significantly upregulated. The expressions of CREB and GLUT2 decreased significantly, while GLUT1 increased significantly. Moreover, glycogen content, glycogen synthase and glycogen phosphorylase activities in hepatopancreas and muscle were significantly increased. Furthermore, the levels of key enzymes HK, PK and PFK in glycolysis, rate-limiting enzymes CS in TCA, and critical enzymes PEPCK, FBP and G6P in gluconeogenesis were significantly decreased in hepatopancreas. These results suggest that CHH affects DA, and then they affect their receptors respectively to transmit glucose metabolism signals into the hepatopancreas of L. vannamei under ammonia-N stress. CHH acts on cGMP-PKG-AMPKα-CREB pathway through GC, and CHH affects DA to influence cAMP-PKA-AMPKγ-CREB and DAG-PKC-AMPKβ-CREB pathways, thereby regulating GLUTs, inhibiting glycogen metabolism and promoting glycolysis and gluconeogenesis. This study contributes to further understand glucose metabolism mechanism of crustacean in response to environmental stress.

Control of hepatic glycogen metabolism in the rhesus monkey: effect of glucose, insulin, and glucagon administration

1975 ◽  
Vol 228 (1) ◽  
pp. 80-87 ◽  
Author(s):  
RT Curnow ◽  
EJ Rayfield ◽  
DT George ◽  
TV Zenser ◽  
F De Rubertis
Keyword(s):  
Rhesus Monkey ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Hepatic Glycogen ◽  
Insulin Administration ◽  
Intravenous Glucose ◽  
Camp System ◽  
Effect Of Glucose ◽  
Insulin Inhibition

The effects of intravenous glucose, insulin and glucagon admininistration on the hepatic glycogen synthase and glycogen phosphorylase systems were assessed in the anesthetized rhesus monkey. Results were correlated with measurements of hepatic cyclic AMP (cAMP) concentrations and plasma glucose, insulin, and glucagon concentrations. Both glucose and insulin administration promoted significant inactivation of phosphorylase by 1 min, which was followed by more gradual activation of synthase. Neither glucose nor insulin caused significant changes in hepatic cAMP. Marked hyperglucagonemia resulting from insulin-induced hypoglycemia did not cause increases IN in hepatic cAMP, suggesting that the elevated insulin levels possibly inhibited glucagon action on the hepatic adenylate cyclase-cAMP system. Glucagon administration caused large increases in hepatic cAMP and activation of phosphorylase within 1 min, followed by more gradual inactivation of synthase when it had been previously activated by glucose. Concomitant glucose infusion, with resulting increased plasma insulin concentrations, markedly diminished the duration of hepatic cAMP elevations following glucagon adminstration, again suggesting an insulin inhibition of glucagon action on the hepatic adenylate-cAMP system.

scholarly journals Fructose-induced increase in intracellular free Mg2+ ion concentration in rat hepatocytes: relation with the enzymes of glycogen metabolism

1997 ◽  
Vol 326 (3) ◽  
pp. 823-827 ◽  
Author(s):  
Vinciane GAUSSIN ◽  
Philippe GAILLY ◽  
Jean-Marie GILLIS ◽  
Louis HUE
Keyword(s):  
Glycogen Phosphorylase ◽  
Time Course ◽  
Buffer Capacity ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Rat Hepatocytes ◽  
Glycogen Metabolism ◽  
Dose Dependence ◽  
Ion Concentration ◽  
Extracellular Medium

In rat hepatocytes subjected to a fructose load, ATP content decreased from 3.8 to 2.6 μmol/g of cells. Under these conditions, the intracellular free Mg2+ ion concentration, as measured with mag-fura 2, increased from 0.25 to 0.43 μmol/g of cells and 0.35 μmol of Mg2+ ions were released per g of cells in the extracellular medium. Therefore the increase in the intracellular free Mg2+ ion concentration was less than expected from the decrease in ATP, indicating that approx. 80% of the Mg2+ ions released from MgATP2- were buffered inside the cells. When this buffer capacity was challenged with an extra Mg2+ ion load by blocking the fructose-induced Mg2+ efflux, again approx. 80% of the extra Mg2+ ion load was buffered. The remaining 20% appearing as free Mg2+ ions in fructose-treated hepatocytes could act as second messenger for enzymes having a Km for Mg2+ in the millimolar range. Fructose activated glycogen synthase and glycogen phosphorylase, although both the time course and the dose-dependence of activation were different. This was reflected in a stimulation of glycogen synthesis with concentrations of fructose below 5 mM. Indeed, activation of glycogen synthase reached a maximum at 30 min of incubation and was observed with small (5 mM or less) concentrations of fructose, whereas the activation of glycogen phosphorylase was almost immediate (within 5 min) and maximal with large doses of fructose. The fructose-induced activation of glycogen phosphorylase, but not that of glycogen synthase, could be related to an increase in free Mg2+ ion concentration.

scholarly journals Diverse effects of two allosteric inhibitors on the phosphorylation state of glycogen phosphorylase in hepatocytes

2002 ◽  
Vol 368 (1) ◽  
pp. 309-316 ◽  
Author(s):  
Theodore LATSIS ◽  
Birgitte ANDERSEN ◽  
Loranne AGIUS
Keyword(s):  
Glycogen Phosphorylase ◽  
Potent Inhibitor ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Small Degree ◽  
Allosteric Inhibitors ◽  
Phosphorylation State ◽  
Stimulation Of

Two distinct allosteric inhibitors of glycogen phosphorylase, 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) and CP-91149 (an indole-2-carboxamide), were investigated for their effects on the phosphorylation state of the enzyme in hepatocytes in vitro. CP-91149 induced inactivation (dephosphorylation) of phosphorylase in the absence of hormones and partially counteracted the phosphorylation caused by glucagon. Inhibition of glycogenolysis by CP-91149 can be explained by dephosphorylation of phosphorylase a. This was associated with activation of glycogen synthase and stimulation of glycogen synthesis. DAB, in contrast, induced a small degree of phosphorylation of phosphorylase. This was associated with inactivation of glycogen synthase and inhibition of glycogen synthesis. Despite causing phosphorylation (activation) of phosphorylase, DAB is a very potent inhibitor of glycogenolysis in both the absence and presence of glucagon. This is explained by allosteric inhibition of phosphorylase a, which overrides the increase in activation state. In conclusion, two potent phosphorylase inhibitors exert different effects on glycogen metabolism in intact hepatocytes as a result of opposite effects on the phosphorylation state of both phosphorylase and glycogen synthase.

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