Glucose 6-phosphate causes translocation of phosphorylase in hepatocytes and inactivates the enzyme synergistically with glucose

Aiston, Susan; Green, Andrew; Mukhtar, Mohammed Hasan; Agius, Loranne

doi:10.1042/bj20031191

Cited by 36 publications

(62 citation statements)

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“…Fig. 10 shows a tentative model for the changes in distribution (between soluble and particulate fractions) and in the activation state of glycogen synthase and phosphorylase in response to the stimuli tested in the present and previous studies (3,29). Translocation of glycogen synthase and phosphorylase a occurs in tandem in response to elevated glucose-6-P (3,23) or PTG expression (present study).…”

Section: Ptg Expression Counteracts the Acute And Sustained Activatiomentioning

confidence: 91%

“…High glucose concentration suppresses glycogenolysis not only through glucose-mediated allosteric inhibition of phosphorylase a and dephosphorylation (1) but also through glucose-6-P-mediated dephosphorylation of phosphorylase a and translocation (3,23). Two explanations are possible for the lack of additive effects of glucose and PTG on inactivation of phosphorylase a.…”

Section: Ptg Expression Counteracts the Acute And Sustained Activatiomentioning

confidence: 94%

“…Phosphorylase a was assayed in the supernatant spectrometrically in the glycogenolytic direction and is expressed as milliunits/mg protein (15). Distribution of phosphorylase a between the pellet and supernatant was determined radiochemically (3,23) from the incorporation of [1-14 C]glucose-1-P into glycogen (25) and expressed as pellet percentage of the total. Activities were found to be 2-fold higher by the radiochemical assay compared with the spectrometric assay (3).…”

Section: Methodsmentioning

confidence: 99%

“…PTG Overexpression Causes Translocation of Phosphorylase a to the Pellet-Because glucose-6-P causes translocation of phosphorylase (determined enzymatically or by immunoblotting (3,23)) as well as glycogen synthase from the supernatant to the pellet (26, 28), we tested the combined effects of PTG and glucokinase expression on the distribution of phosphorylase. There was an additive effect of glucokinase and PTG on translocation of phosphorylase a (Fig.…”

Section: Effects Of Ptg Are Additive With Glucokinase Expression But mentioning

confidence: 99%

“…Regulation of liver glycogen metabolism by hormones and substrates is mediated by changes in the phosphorylation state of glycogen synthase and phosphorylase and by subcellular translocation of these proteins (1)(2)(3). Dephosphorylation is catalyzed by PP1C 1 in association with glycogen-targeting proteins (4), of which three isoforms are expressed in liver, designated G L , PTG, and R6 (5).…”

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confidence: 99%

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The Glycogenic Action of Protein Targeting to Glycogen in Hepatocytes Involves Multiple Mechanisms Including Phosphorylase Inactivation and Glycogen Synthase Translocation

Green

Aiston

Greenberg

et al. 2004

Journal of Biological Chemistry

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Expression of the glycogen-targeting protein PTG promotes glycogen synthase activation and glycogen storage in various cell types. In this study, we tested the contribution of phosphorylase inactivation to the glycogenic action of PTG in hepatocytes by using a selective inhibitor of phosphorylase (CP-91149) that causes dephosphorylation of phosphorylase a and sequential activation of glycogen synthase. Similar to CP-91194, graded expression of PTG caused a concentration-dependent inactivation of phosphorylase and activation of glycogen synthase. The latter was partially counteracted by the expression of muscle phosphorylase and was not additive with the activation by CP-91149, indicating that it is in part secondary to the inactivation of phosphorylase. PTG expression caused greater stimulation of glycogen synthesis and translocation of glycogen synthase than CP-91149, and the translocation of synthase could not be explained by accumulation of glycogen, supporting an additional role for glycogen synthase translocation in the glycogenic action of PTG. The effects of PTG expression on glycogen synthase and glycogen synthesis were additive with the effects of glucokinase expression, confirming the complementary roles of depletion of phosphorylase a (a negative modulator) and elevated glucose 6-phosphate (a positive modulator) in potentiating the activation of glycogen synthase. PTG expression mimicked the inactivation of phosphorylase caused by high glucose and counteracted the activation caused by glucagon. The latter suggests a possible additional role for PTG on phosphorylase kinase inactivation.Regulation of liver glycogen metabolism by hormones and substrates is mediated by changes in the phosphorylation state of glycogen synthase and phosphorylase and by subcellular translocation of these proteins (1-3). Dephosphorylation is catalyzed by PP1C 1 in association with glycogen-targeting proteins (4), of which three isoforms are expressed in liver, designated G L , PTG, and R6 (5). All isoforms have glycogensynthase phosphatase and phosphorylase phosphatase activity when assayed in vitro; however, the synthase phosphatase/ phosphorylase phosphatase ratio is higher for G L -PP1 than for PTG-PP1, suggesting that G L may be the predominant synthase phosphatase (5). G L (R4) is expressed predominantly in liver and to a lesser extent in heart and human skeletal muscle (6, 7), PTG is expressed in several tissues including liver and skeletal muscle (8 -10), and R6 is expressed ubiquitously (11). Both G L and PTG show adaptive changes in expression in rat liver in response to changes in insulin status (5), and the physiological role of these changes has been confirmed from studies (12, 13) in hepatocytes, which showed glycogen synthase activation and increased glycogen storage when G L and PTG were overexpressed.A unique property of G L is its allosteric binding site for phosphorylase a, which accounts for the inhibition of glycogensynthase phosphatase activity by low concentrations of phosphorylase a (5). This mechanism ...

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Section: Ptg Expression Counteracts the Acute And Sustained Activatiomentioning

confidence: 91%

Section: Ptg Expression Counteracts the Acute And Sustained Activatiomentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Effects Of Ptg Are Additive With Glucokinase Expression But mentioning

confidence: 99%

mentioning

confidence: 99%

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The Glycogenic Action of Protein Targeting to Glycogen in Hepatocytes Involves Multiple Mechanisms Including Phosphorylase Inactivation and Glycogen Synthase Translocation

Green

Aiston

Greenberg

et al. 2004

Journal of Biological Chemistry

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Determining the state of a process control system: Current trends and future challenges

Shardt

Zhao

et al. 2011

Can J Chem Eng

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In many industrial plants, multiple, interconnected control loops are common. Their maintenance and improvement requires detailed controller performance assessment to determine not only whether they are behaving well, but also to determine the potential cause of any observed problems. Techniques for performance assessment can be divided into two broad categories (1) performance assessment of regulatory control loops; and (2) performance assessment of supervisory control loops that evaluate the economic performance of advanced control strategies, such as model predictive control (MPC). A comprehensive review of the literature on the industrial applications of performance assessment, as well as some of the currently available software, is also presented. © 2011 Canadian Society for Chemical Engineering

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The role of protein translocation in the regulation of glycogen metabolism

Jurczak

Danos

Rehrmann

et al. 2007

J of Cellular Biochemistry

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Early biochemical analyses of metabolic pathways assumed that the free diffusion of substrates and enzymes in an evenly mixed cellular space provided the interactions that enabled reactions to proceed. Metabolic complexes have since been shown to assemble and disassemble in response to changes in cellular conditions, and in turn, to channel metabolic intermediates within discreet cellular compartments, allowing for the efficient use or storage of energy. A fundamental component to the formation of metabolic complexes and the channeling of metabolites is the translocation of enzymes in response to specific extra-and intracellular signals. These generalities play an important role in the metabolism of glucose to glycogen within skeletal muscle and liver. In this review, the similarities and differences in skeletal muscle and liver glucose metabolism with regards to glucose transport and intracellular processing will be addressed during the fasted to fed transition. More specifically, the importance of isoform expression and protein translocation in the tissue specific control of glucose homeostasis will be covered.

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Glucose 6-phosphate causes translocation of phosphorylase in hepatocytes and inactivates the enzyme synergistically with glucose

Cited by 36 publications

References 48 publications

The Glycogenic Action of Protein Targeting to Glycogen in Hepatocytes Involves Multiple Mechanisms Including Phosphorylase Inactivation and Glycogen Synthase Translocation

The Glycogenic Action of Protein Targeting to Glycogen in Hepatocytes Involves Multiple Mechanisms Including Phosphorylase Inactivation and Glycogen Synthase Translocation

Determining the state of a process control system: Current trends and future challenges

The role of protein translocation in the regulation of glycogen metabolism

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