scholarly journals Regulatory phosphorylation site tunes Phosphoglucomutase 1 as a metabolic valve to control mobilization of glycogen stores.

2021 ◽  
Author(s):  
Sofia Doello ◽  
Niels Neumann ◽  
Philipp Spaet ◽  
Boris Macek ◽  
Karl Forchhammer
Keyword(s):  
Glycogen Synthesis ◽  
Phosphorylation Site ◽  
Glycogen Metabolism ◽  
Pentose Phosphate ◽  
Unicellular Cyanobacterium ◽  
Metabolic Channeling ◽  
Protein Protein Interaction ◽  
Steady State Levels ◽  
Glycogen Stores ◽  
Synthesis And Degradation

Regulation of glycogen metabolism is of vital importance in organisms of all three kingdoms of life. Although the pathways involved in glycogen synthesis and degradation are well known, many regulatory aspects around the metabolism of this polysaccharide remain undeciphered. Here, we used the unicellular cyanobacterium Synechocystis as a model to investigate how glycogen metabolism is regulated in dormant nitrogen-starved cells, which entirely rely on glycogen catabolism to restore growth. We found that the activity of the enzymes involved in glycogen synthesis and degradation is tightly controlled at different levels via post-translational modifications. Phosphorylation of phosphoglucomutase 1 (Pgm1) on a peripheral residue (Ser63) regulates Pgm1 activity and controls the mobilization of the glycogen stores. Inhibition of Pgm1 activity via phosphorylation on Ser63 appears essential for survival of Synechocystis in the dormant state. Remarkably, this regulatory mechanism seems to be conserved from bacteria to humans. Moreover, phosphorylation of Pgm1 influences the formation of a metabolon, which includes Pgm1, oxidative pentose phosphate cycle protein (OpcA) and glucose-6-phosphate dehydrogenase (G6PDH). Analysis of the steady-state levels of the metabolic products of glycogen degradation together with protein-protein interaction studies revealed that the activity of G6PDH and the formation of this metabolon are under additional redox control, likely to ensure metabolic channeling of glucose-6-phosphate to the required pathways for each developmental stage.

Synthesis and degradation of glycogen by Schistosoma mansoni worms in vitro

Parasitology ◽  
1989 ◽  
Vol 98 (1) ◽  
pp. 67-73 ◽  
Author(s):  
A. G. M. Tielens ◽  
C. Celik ◽  
J. M. Van Den Heuvel ◽  
R. H. Elfring ◽  
S. G. Van Den Bergh
Keyword(s):  
Schistosoma Mansoni ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Krebs Cycle ◽  
Glycogen Metabolism ◽  
Mammalian Host ◽  
Initial Reduction ◽  
Glycogen Stores ◽  
Synthesis And Degradation

SummaryThe glycogen stores of adult Schistosoma mansoni worms could be labelled by incubation of the worms, after an initial reduction of their glycogen content, in the presence of [6-14C]glucose. Subsequent breakdown of the labelled glycogen by the parasite revealed that glycogen was degraded to lactate and carbon dioxide. The degradation of glycogen, as compared to that of glucose, resulted in slightly different ratios of these two end-products. This indicates that glycogen breakdown did not replace glucose breakdown to the same extent in all cells and that Krebs-cycle activity was not uniformly distributed throughout the cells of this parasite. Both fructose and mannose could replace glucose as an energy source and the rate of glycogen synthesis from either of these two carbohydrates was higher than from glucose. No indications for glyconeogenesis from C3-units were found. Glycogen metabolism of S. mansoni was not influenced by hormones of the mammalian host. It is regulated by the external glucose concentration and by the level of the endogenous glycogen stores. Studies on paired and unpaired worms showed that no interaction between male and female was necessary for the synthesis of glycogen by female worms.

scholarly journals Assessment of glycogen turnover in aerobic, ischemic, and reperfused working rat hearts

1998 ◽  
Vol 275 (5) ◽  
pp. H1533-H1541 ◽  
Author(s):  
Heather Fraser ◽  
Gary D. Lopaschuk ◽  
Alexander S. Clanachan
Keyword(s):  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Low Flow ◽  
Turnover Rates ◽  
Myocardial Glucose Metabolism ◽  
Rat Hearts ◽  
Simultaneous Synthesis ◽  
Postischemic Recovery ◽  
Synthesis And Degradation ◽  
Glycogen Turnover

Glycogen and its turnover are important components of myocardial glucose metabolism that significantly impact on postischemic recovery. We developed a method to measure glycogen turnover (rates of glycogen synthesis and degradation) in isolated working rat hearts using [3H]- and [14C]glucose. In aerobic hearts perfused with 11 mM glucose, 1.2 mM palmitate, and 100 μU/ml insulin, rates of glycogen synthesis and degradation were 1.24 ± 0.3 and 0.53 ± 0.25 μmol ⋅ min−1 ⋅ g dry wt−1, respectively. Low-flow ischemia (0.5 ml/min, 60 min) elicited a marked glycogenolysis; rates of glycogen synthesis and degradation were 0.54 ± 0.16 and 2.12 ± 0.14 μmol ⋅ min−1 ⋅ g dry wt−1, respectively. During reperfusion (30 min), mechanical function recovered to 20% of preischemic values. Rates of synthesis and degradation were 1.66 ± 0.16 and 1.55 ± 0.21 μmol ⋅ min−1 ⋅ g dry wt−1, respectively, and glycogen content remained unchanged (25 ± 3 μmol/g dry wt). The assessment of glycogen metabolism needs to take into account the simultaneous synthesis and degradation of glycogen. With this approach, a substantial turnover of glycogen was detectable not only during aerobic conditions but also during ischemia as well as reperfusion.

Enhanced muscle glucose metabolism after exercise: modulation by local factors

1984 ◽  
Vol 246 (6) ◽  
pp. E476-E482 ◽  
Author(s):  
E. A. Richter ◽  
L. P. Garetto ◽  
M. N. Goodman ◽  
N. B. Ruderman
Keyword(s):  
Glucose Utilization ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Voluntary Exercise ◽  
Local Contraction ◽  
Glucose Incorporation ◽  
Systemic Factors ◽  
Glycogen Repletion ◽  
Two Phases ◽  
Glycogen Stores

Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase in the presence of insulin is found. To determine whether these alterations and in particular those mediated by insulin are due to local or systemic factors, one hindlimb of an anesthetized rat was electrically stimulated, and both hindlimbs were perfused immediately thereafter. Glucose and glycogen metabolism in the stimulated leg closely mimicked that observed previously after voluntary exercise on a treadmill. With no insulin added to the perfusate, glucose incorporation into glycogen was markedly enhanced in muscles that were glycogen depleted as were the uptake of 2-deoxyglucose and 3-O-methylglucose. Likewise, the stimulation of these processes by insulin was enhanced and continued to be so 2 h later when the muscles of the stimulated leg had substantially repleted their glycogen stores. The results suggest that the increases in insulin-mediated glucose utilization and glycogen synthesis in muscle after exercise are modulated by local contraction-induced factors.

scholarly journals Central Role for Protein Targeting to Glycogen in the Maintenance of Cellular Glycogen Stores in 3T3-L1 Adipocytes

2006 ◽  
Vol 26 (1) ◽  
pp. 334-342 ◽  
Author(s):  
Cynthia C. Greenberg ◽  
Arpad M. Danos ◽  
Matthew J. Brady
Keyword(s):  
Protein Targeting ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Critical Role ◽  
Glycogen Metabolism ◽  
Metabolizing Enzymes ◽  
Protein Levels ◽  
Extracellular Glucose ◽  
Interfering Rna ◽  
Glycogen Stores

ABSTRACT Overexpression of the protein phosphatase 1 (PP1) subunit protein targeting to glycogen (PTG) markedly enhances cellular glycogen levels. In order to disrupt the endogenous PTG-PP1 complex, small interfering RNA (siRNA) constructs against PTG were identified. Infection of 3T3-L1 adipocytes with PTG siRNA adenovirus decreased PTG mRNA and protein levels by >90%. In parallel, PTG reduction resulted in a >85% decrease in glycogen levels 4 days after infection, supporting a critical role for PTG in glycogen metabolism. Total PP1, glycogen synthase, and GLUT4 levels, as well as insulin-stimulated signaling cascades, were unaffected. However, PTG knockdown reduced glycogen-targeted PP1 protein levels, corresponding to decreased cellular glycogen synthase- and phosphorylase-directed PP1 activity. Interestingly, GLUT1 levels and acute insulin-stimulated glycogen synthesis rates were increased two- to threefold, and glycogen synthase activation in the presence of extracellular glucose was maintained. In contrast, glycogenolysis rates were markedly increased, suggesting that PTG primarily acts to suppress glycogen breakdown. Cumulatively, these data indicate that disruption of PTG expression resulted in the uncoupling of PP1 activity from glycogen metabolizing enzymes, the enhancement of glycogenolysis, and a dramatic decrease in cellular glycogen levels. Further, they suggest that reduction of glycogen stores induced cellular compensation by several mechanisms, but ultimately these changes could not overcome the loss of PTG expression.

scholarly journals Sequestration of host metabolism by an intracellular pathogen

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Lena Gehre ◽  
Olivier Gorgette ◽  
Stéphanie Perrinet ◽  
Marie-Christine Prevost ◽  
Mathieu Ducatez ◽  
...  
Keyword(s):  
De Novo ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Strong Support ◽  
Glycogen Metabolism ◽  
Metabolism Enzymes ◽  
The Cost ◽  
Type 3 ◽  
Glycogen Stores ◽  
Host Metabolism

For intracellular pathogens, residence in a vacuole provides a shelter against cytosolic host defense to the cost of limited access to nutrients. The human pathogen Chlamydia trachomatis grows in a glycogen-rich vacuole. How this large polymer accumulates there is unknown. We reveal that host glycogen stores shift to the vacuole through two pathways: bulk uptake from the cytoplasmic pool, and de novo synthesis. We provide evidence that bacterial glycogen metabolism enzymes are secreted into the vacuole lumen through type 3 secretion. Our data bring strong support to the following scenario: bacteria co-opt the host transporter SLC35D2 to import UDP-glucose into the vacuole, where it serves as substrate for de novo glycogen synthesis, through a remarkable adaptation of the bacterial glycogen synthase. Based on these findings we propose that parasitophorous vacuoles not only offer protection but also provide a microorganism-controlled metabolically active compartment essential for redirecting host resources to the pathogens.

Abstract 100: Integrated Cardiac Metabolism In End-Stage Human Heart Failure

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Emily Flam ◽  
Cholsoon Jang ◽  
Ken Bedi ◽  
Danielle Murashige ◽  
Yifan Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Human Heart ◽  
Glycogen Synthesis ◽  
Cardiac Metabolism ◽  
Pentose Phosphate ◽  
Metabolic Changes ◽  
Phospholipid Content ◽  
Human Heart Failure ◽  
Nucleotide Synthesis ◽  
End Stage

Heart failure affects millions of people worldwide with mortality near 50% within five years. This disease is characterized by widespread cardiac and systemic metabolic changes, but a comprehensive evaluation of metabolism in failing human hearts is lacking. Here, we provide a comprehensive depiction of cardiac and systemic metabolic changes in 89 explanted failing and non-failing human hearts through integration of plasma and cardiac tissue metabolomics, genome-wide RNAseq, and proteomic data. The data confirm a profound bioenergetic defect in end-stage human heart failure and demonstrate extensive changes in metabolic homeostasis. The data indicate a substantial defect in fatty acid (FA) use in failing hearts, in particular unsaturated FAs. Reduction of FAs and acyl-carnitines in failing tissue in contrast to concomitant elevations in plasma suggest a defect in import of FAs into the cell, rather than a defect in FA oxidation. Intermediates of glycolysis, the pentose phosphate pathway, and glycogen synthesis are all similarly reduced, as is expression of GLUT1, indicating diminished glucose uptake. However, there was no significant change in tissue pyruvate content, suggesting an increase in lactate utilization. The data suggest increased flux of pyruvate into mitochondria, likely promoting pyruvate oxidation but not pyruvate carboxylation. Blunted anabolic pyruvate flux, in turn, likely leads to insufficient TCA cycle intermediates. Ketone levels were increased in both failing tissue and plasma, as previously reported. The phospholipid content of failing human hearts is greatly increased in both failing tissue and plasma. Nucleotide synthesis pathways also appear to be reprogrammed, with a notable decrease in adenosine metabolism, specifically. Together, these data indicate widespread change in the local cardiac and greater systemic metabolic landscape in severe human heart failure.

scholarly journals Estrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy

2021 ◽  
Vol 8 ◽  
Author(s):  
Xinbo Wang ◽  
Yuming Zhang ◽  
Yansong Li ◽  
Mingyu Tang ◽  
Qinghua Deng ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Opposite Effect ◽  
Glycogen Synthesis ◽  
Perinatal Period ◽  
Negative Energy ◽  
Pentose Phosphate ◽  
Polymorphonuclear Neutrophils ◽  
Atp Content ◽  
Gsk 3Β ◽  
Immune Potential

Hypoglycemia resulting from a negative energy balance (NEB) in periparturient cattle is the major reason for a reduced glycogen content in polymorphonuclear neutrophils (PMNs). The lack of glycogen induces PMNs dysfunction and is responsible for the high incidence of perinatal diseases. The perinatal period is accompanied by dramatic changes in sex hormones levels of which estrogen (17β-estradiol, E2) has been shown to be closely associated with PMNs function. However, the precise regulatory mechanism of E2 on glucose metabolism in cattle PMNs has not been elucidated. Cattle PMNs were cultured in RPMI 1640 with 2.5 (LG), 5.5 (NG) and 25 (HG) mM glucose and E2 at 20 (EL), 200 (EM) and 450 (EH) pg/mL. We found that E2 maintained PMNs viability in different glucose conditions, and promoted glycogen synthesis by inhibiting PFK1, G6PDH and GSK-3β activity in LG while enhancing PFK1 and G6PDH activity and inhibiting GSK-3β activity in HG. E2 increased the ATP content in LG but decreased it in HG. This indicated that the E2-induced increase/decrease of ATP content may be independent of glycolysis and the pentose phosphate pathway (PPP). Further analysis showed that E2 promoted the activity of hexokinase (HK) and GLUT1, GLUT4 and SGLT1 expression in LG, while inhibiting GLUT1, GLUT4 and SGLT1 expression in HG. Finally, we found that E2 increased LC3, ATG5 and Beclin1 expression, inhibited p62 expression, promoting AMPK-dependent autophagy in LG, but with the opposite effect in HG. Moreover, E2 increased the Bcl-2/Bax ratio and decreased the apoptosis rate of PMNs in LG but had the opposite effect in HG. These results showed that E2 could promote AMPK-dependent autophagy and inhibit apoptosis in response to glucose-deficient environments. This study elucidated the detailed mechanism by which E2 promotes glycogen storage through enhancing glucose uptake and retarding glycolysis and the PPP in LG. Autophagy is essential for providing ATP to maintain the survival and immune potential of PMNs. These results provided significant evidence for further understanding the effects of E2 on PMNs immune potential during the hypoglycemia accompanying perinatal NEB in cattle.

Synergistic effects of oPL and insulin on glycogen metabolism in fetal rat hepatocytes

1984 ◽  
Vol 247 (6) ◽  
pp. E714-E718
Author(s):  
M. Freemark ◽  
S. Handwerger
Keyword(s):  
Synergistic Effects ◽  
Fetal Liver ◽  
Glycogen Synthesis ◽  
Rat Hepatocytes ◽  
Glycogen Metabolism ◽  
Placental Lactogen ◽  
Maximum Effect ◽  
Hepatic Glycogen ◽  
Response Curves ◽  
Glucose Incorporation

The interactions between ovine placental lactogen (oPL) and insulin in the regulation of fetal liver glycogen metabolism have been studied in cultured hepatocytes from fetal rats on day 20 of gestation. Both oPL (0.75–22.5 micrograms/ml) and insulin (0.01–1 microM) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen. However, the dose-response curves for the two hormones were not parallel and the maximum effect of oPL was 3.4 times greater than that of insulin (P less than 0.001). The two hormones had synergistic effects on [14C]glucose incorporation at low concentrations and additive effects at maximum concentrations. Ovine growth hormone (oGH) also stimulated [14C]glucose incorporation into glycogen but with a potency only 12.3% that of oPL. Cycloheximide (20 microM) abolished the stimulation of [14C]glucose incorporation by insulin (1 microM), oPL (5 micrograms/ml), and oGH (100 micrograms/ml). Although the glycogenic actions of oPL and insulin may depend on new protein synthesis, the results of these studies suggest that these hormones stimulate glycogen synthesis in fetal liver by different mechanisms. Because the glycogenic actions of oPL are potentiated by insulin, these hormones may act in concert to promote hepatic glycogen storage in the fetus.

Glucose metabolism in epitrochlearis muscle of acutely exercised and trained rats

1986 ◽  
Vol 250 (2) ◽  
pp. E137-E143 ◽  
Author(s):  
T. A. Davis ◽  
S. Klahr ◽  
E. D. Tegtmeyer ◽  
D. F. Osborne ◽  
T. L. Howard ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Acute Exercise ◽  
Glycogen Synthesis ◽  
Prior Training ◽  
Glycogen Stores

Effects of insulin on glycogen synthesis (GS), glycolytic utilization (GU), and glucose uptake (GT) were studied in isolated epitrochlearis muscles from exercise-trained or sedentary rats during recovery from acute exercise or at rest. During the 1st h after acute exercise, the enhanced basal and insulin-stimulated GT was directed mainly toward replenishment of glycogen but basal GU was also increased. During the second through third hours after exercise, basal GS decreased but remained greater than rest and basal GU and GT returned to normal. Insulin sensitivity of these parameters was enhanced. Training alone reduced basal GS but enhanced insulin sensitivity of GT and GU. Training reduced the acute exercise-stimulated increase in basal and insulin sensitivity of GS during recovery from acute exercise, probably due to elevated glycogen stores. Thus recovery from acute exercise or training, either alone or in combination, enhances insulin stimulated GT in muscle; however, the increased glucose is primarily channeled toward GS after acute exercise, which is reduced by prior training and is directed to GU in trained animals either at rest or after acute exercise.

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