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

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.

2021 ◽  
Author(s):  
Sofia Doello ◽  
Niels Neumann ◽  
Philipp Spaet ◽  
Boris Macek ◽  
Karl Forchhammer

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.


1966 ◽  
Vol 51 (2) ◽  
pp. 193-202
Author(s):  
J. A. Antonioli ◽  
A. Vannotti

ABSTRACT 1. The metabolism of suspensions of circulating leucocytes has been studied after intramuscular injection of a dose of 50 mg/kg of a corticosteroid (cortisone acetate). The suspensions were incubated under aerobic conditions in the presence of a glucose concentration of 5.6 mm. Glucose consumption, lactate production, and variations in intracellular glycogen concentration were measured. After the administration of the corticosteroid, the anabolic processes of granulocyte metabolism were reversibly stimulated. Glucose consumption and lactate production increased 12 hours after the injection, but tended to normalize after 24 hours. The glycogen content of the granulocytes was enhanced, and glycogen synthesis during the course of the incubation was greatly stimulated. The action of the administered corticosteroid is more prolonged in females than in males. The injection of the corticosteroid caused metabolic modifications which resemble in their modulations and in their chronological development those found in circulating granulocytes of guinea-pigs suffering from sterile peritonitis. These results suggest, therefore, that, in the case of acute inflammation, the glucocorticosteroids may play an important role in the regulation of the metabolism of the blood leucocytes.


1998 ◽  
Vol 275 (5) ◽  
pp. H1533-H1541 ◽  
Author(s):  
Heather Fraser ◽  
Gary D. Lopaschuk ◽  
Alexander S. Clanachan

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.


2010 ◽  
Vol 76 (20) ◽  
pp. 6910-6919 ◽  
Author(s):  
Han Min Woo ◽  
Stephan Noack ◽  
Gerd M. Seibold ◽  
Sabine Willbold ◽  
Bernhard J. Eikmanns ◽  
...  

ABSTRACT In this study, we analyzed the influence of phosphate (Pi) limitation on the metabolism of Corynebacterium glutamicum. Metabolite analysis by gas chromatography-time-of-flight (GC-TOF) mass spectrometry of cells cultivated in glucose minimal medium revealed a greatly increased maltose level under Pi limitation. As maltose formation could be linked to glycogen metabolism, the cellular glycogen content was determined. Unlike in cells grown under Pi excess, the glycogen level in Pi-limited cells remained high in the stationary phase. Surprisingly, even acetate-grown cells, which do not form glycogen under Pi excess, did so under Pi limitation and also retained it in stationary phase. Expression of pgm and glgC, encoding the first two enzymes of glycogen synthesis, phosphoglucomutase and ADP-glucose pyrophosphorylase, was found to be increased 6- and 3-fold under Pi limitation, respectively. Increased glycogen synthesis together with a decreased glycogen degradation might be responsible for the altered glycogen metabolism. Independent from these experimental results, flux balance analysis suggested that an increased carbon flux to glycogen is a solution for C. glutamicum to adapt carbon metabolism to limited Pi concentrations.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kasandra S. Hunter ◽  
André Miller ◽  
Margaret Mentink-Kane ◽  
Stephen J. Davies

On entering the mammalian host, schistosomes transition from a freshwater environment where resources are scarce, to an environment where there is an unlimited supply of glucose, their preferred energy substrate. Adult schistosome glycolytic activity consumes almost five times the parasite’s dry weight in glucose per day to meet the parasite’s energy demands, and the schistosome glycolytic enzymes and mechanisms for glucose uptake that sustain this metabolic activity have previously been identified. However, little is known of the parasite processes that regulate schistosome glucose metabolism. We previously described the Schistosoma mansoni ortholog of 5′ AMP-Activated Protein Kinase (AMPK), which is a central regulator of energy metabolism in eukaryotes, and characterized the developmental regulation of its expression and activity in S. mansoni. Here we sought to explore the function of AMPK in schistosomes and test whether it regulates parasite glycolysis. Adult schistosomes mounted a compensatory response to chemical inhibition of AMPK α, resulting in increased AMPK α protein abundance and activity. RNAi inhibition of AMPK α expression, however, suggests that AMPK α is not required for adult schistosome viability in vitro. Larval schistosomula, on the other hand, are sensitive to chemical AMPK α inhibition, and this correlates with inactivity of the AMPK α gene in this life cycle stage that precludes a compensatory response to AMPK inhibition. While our data indicate that AMPK is not essential in adult schistosomes, our results suggest that AMPK regulates adult worm glycogen stores, influencing both glycogen utilization and synthesis. AMPK may therefore play a role in the ability of adult schistosomes to survive in vivo stressors such as transient glucose deprivation and oxidative stress. These findings suggest that AMPK warrants further investigation as a potential drug target, especially for interventions aimed at preventing establishment of a schistosome infection.


1963 ◽  
Vol 44 (1) ◽  
pp. 90-100
Author(s):  
P. R. Bouman ◽  
W. Dermer

ABSTRACT The in vitro effects of adrenaline on glycogen metabolism and glucose uptake were studied in diaphragms of intact, adrenalectomized and adrenodemedullated rats decapitated under »Nembutal« anaesthesia. Adrenalectomy and pretreatment of adrenalectomized rats with cortisol caused an increase in the net loss of glycogen induced by adrenaline. When glycogen deposition in the absence of adrenaline was also taken into account, the overall magnitude of the glycogenolytic response appeared to be unchanged. The apparent qualitative change in response induced by these procedures was attributed to increased initial glycogen values. In diaphragms of adrenalectomized and adrenodemedullated rats the response to adrenaline was identical, the initial glycogen content being the same in these preparations. None of the experimental procedures affected the variable inhibition of glucose uptake by adrenaline. These results do not favour the existence of a »permissive« or synergistic action of adrenocortical steroids with regard to the effects of adrenaline on peripheral carbohydrate metabolism.


1960 ◽  
Vol XXXV (IV) ◽  
pp. 541-550 ◽  
Author(s):  
P. R. Bouman ◽  
W. Dermer

ABSTRACT Hemidiaphragms of intact and adrenalectomized rats which had been killed by decapitation, were incubated for 1 hour at 37° C under aerobic conditions. Glucose uptake and glycogen deposition were determined. Addition of adrenaline in vitro (1 μg/ml) caused a substantial decrease in glucose uptake in both types of diaphragms, this decrease being equivalent to a simultaneous inhibition of glycogen deposition. »Nembutal« anaesthesia prior to decapitation was found to alter the response to adrenaline. This change was most clearly observed in diaphragms of adrenalectomized rats. Here, adrenaline mainly affected glycogen metabolism by way of glycogen degradation, whereas the overall magnitude of the response was not materially changed. However, glucose uptake appeared to be only slightly decreased by adrenaline under these conditions. The change in response to adrenaline was attributed to the higher initial glycogen content observed in diaphragms of nembutalized rats. It was suggested that prevention of an acute release of endogenous adrenergic substances, occurring after decapitation of unanaesthetized donor rats, may be the actual cause of this phenomenon. Attention was drawn to the significance of the initial glycogen content as an important factor in carbohydrate metabolism of the isolated rat diaphragm.


Parasitology ◽  
1989 ◽  
Vol 98 (3) ◽  
pp. 409-415 ◽  
Author(s):  
B. E. P. Van Oordt ◽  
A. G. M. Tielens ◽  
S. G. Van Den Bergh

SUMMARYSchistosoma mansoni cercariae in water were shown to possess a largely aerobic energy metabolism, the Krebs cycle being the main terminal of carbohydrate breakdown. A metabolic transition towards a more anaerobic breakdown of carbo-hydrate could be achieved by incubation conditions which also stimulated biological transformation. Incubation of cercariae in a simple salt medium containing 5 mM glucose induced such a metabolic transition: beside carbon dioxide large amounts of lactate and pyruvate were excreted. The results indicate that the production of pyruvate was coupled to electron transfer in the respiratory chain. Some aspects of this unusual pyruvate production are discussed. The observed change in the end-product pattern of carbohydrate breakdown is very rapid: most of the switch occurred within 2 h. Our results show that the metabolic transition was triggered by the biological transformation itself, or by the same event that induces the biological transformation. The metabolic and the biological changes proceeded synchronously.


1992 ◽  
Vol 262 (4) ◽  
pp. E427-E433 ◽  
Author(s):  
L. Coderre ◽  
A. K. Srivastava ◽  
J. L. Chiasson

The effects of hypercorticism on the regulation of glycogen metabolism by insulin in skeletal muscles was examined by using the hindlimb perfusion technique. Rats were injected daily with either saline or dexamethasone (0.4 mg.kg-1.day-1) for 14 days and were studied in the fed or fasted (24 h) state under saline or insulin (1 mU/ml) treatment. In fed controls, insulin resulted in glycogen synthase activation and in enhanced glycogen synthesis. In dexamethasone-treated animals, basal muscle glycogen concentration remained normal, but glycogen synthase activity ratio was decreased in white and red gastrocnemius and plantaris muscles. Furthermore, insulin failed to activate glycogen synthase and glycogen synthesis. In the controls, fasting was associated with decreased glycogen concentrations and with increased glycogen synthase activity ratio in all four groups of muscles (P less than 0.01). Dexamethasone treatment, however, completely abolished the decrease in muscle glycogen content as well as the augmented glycogen synthase activity ratio associated with fasting. Insulin infusion stimulated glycogen synthesis in fasted controls but not in dexamethasone-treated rats. These data therefore indicate that dexamethasone treatment inhibits the stimulatory effect of insulin on glycogen synthase activity and on glycogen synthesis. Furthermore, hypercorticism suppresses the decrease in muscle glycogen content associated with fasting.


Parasitology ◽  
2010 ◽  
Vol 137 (11) ◽  
pp. 1645-1652 ◽  
Author(s):  
M. C. HOLTFRETER ◽  
M. LOEBERMANN ◽  
E. FREI ◽  
D. RIEBOLD ◽  
D. WOLFF ◽  
...  

SUMMARYObjective. Bilharziosis is one of the most important helminthal infections in humans and is caused by blood flukes of the genus Schistosoma. Three different life stages of the parasite occur within the mammalian host: schistosomula located in the skin, pre-adults located in the lung and adult worms located in the portal venous system. Erythrocytes are a major source of nutrient supply for adults. However, sources of nutrition for the developing stages are still unclear. Methods. To investigate whether schistosomula, pre-adults and adults of Schistosoma mansoni ingest human serum albumin (HSA) in vitro, these life stages were incubated with aminofluorescein-labelled human serum albumin (Afl-HSA) for 5 h. To test the uptake of albumin in vivo, the albumin conjugate was given intravenously to S. mansoni infected NMRI mice 24 h before harvesting the 3 life stages. Results. In comparison to the control group schistosomula, pre-adults, and adults showed an accumulation of Afl-HSA within the oesophagus and intestinal caecum in vitro and in vivo. Conclusion. Our findings suggest that albumin seems to be a major source of energy supply for the early schistosomal life stages and an additive energy support for adult worms. Since albumin has been used successfully as a drug carrier for chemotherapeutic substances against malignant disorders, further studies will focus on albumin as a carrier for anthelminthics in a drug-targeting model.


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