Energy metabolism in the developing larval stages of Ancylostoma tubaeforme and Haemonchus contortus: glycolytic and tncarboxylic acid cycle enzymes

Parasitology ◽  
1985 ◽  
Vol 90 (1) ◽  
pp. 169-177 ◽  
Author(s):  
C. O. E. Onwuliri
Keyword(s):  
Energy Metabolism ◽  
Pyruvate Kinase ◽  
Metabolic Pathway ◽  
Haemonchus Contortus ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Aconitate Hydratase ◽  
Acid Cycle ◽  
Infective Larvae

The activities of glycolytic and related enzymes and the tricarboxylic acid cycle enzymes were measured in freshly isolated 1st- (Li), 2nd- (L2) and 3rd-stage (L3) larvae of both Ancylostoma tubaeforme and Haemonchus contortus. All enzymes of the glycolytic pathway were present in all developmental stages of both strongylid nematodes although higher levels of activities were obtained in the pre-infective 1st- and 2nd-stage larvae than in the infective 3rd stage. However, the pre-infective larvae contained lower levels of pyruvate kinase (PK) than the infective larvae. Consequently, the pyruvate kinase to phosphoenolpyruvate carboxykinase (PEPCK) ratios were 0·23 and 0·26 for the L1s and L2s for A. tubaeforme and 0·36 and 0·21 for those of H. contortus respectively. High levels of activity of glucose-6-phosphate dehydrogenase obtained in the bacteriophagous pre-infective larvae were consistent with high rates of morphogenesis and substrate synthesis characteristic of the pre-infective stages. All the tricarboxylic acid cycle enzymes were present in the infective larvae of both nematodes while in the pre-infective Li and L2 stages, the enzymes at the beginning of the cycle, namely aconitate hydratase and NAD-linked isocitrate dehydrogenase, were not detected. A scheme was proposed for the energy metabolism of these developing larvae. In this scheme, the pre-infective larvae were shown to operate an anaerobic metabolic pathway involving the carboxylation of phosphoenolpyruvate (PEP) by phosphoenolpyru vate carboxykinase (PEPCK) to form oxaloacetate (OAA), whereas in the infective larvae the metabolic pathway favouring the direct dephosphorylation of PEP, as in vertebrate tissues, was followed.

Intermediary carbohydrate metabolism in protoscoleces ofEchinococcus granulosus(horse and sheep strains) andE. multilocularis

Parasitology ◽  
1982 ◽  
Vol 84 (2) ◽  
pp. 351-366 ◽  
Author(s):  
D. P. McManus ◽  
J. D. Smyth
Keyword(s):  
Steady State ◽  
Carbohydrate Metabolism ◽  
Pyruvate Kinase ◽  
Energy Production ◽  
Alternative Energy ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
State Content

SUMMARYWith few exceptions, the specific activities of the glycolytic enzymes and the steady-state content of glycolytic and associated intermediates in protoscoleces of the horse (E.g.H) and sheep (E.g.S) strains ofEchinococcus granulosusand the closely relatedE. multilocularis(E.m.) are very similar. Phosphorylase, hexokinase, phosphofructokinase and pyruvate kinase catalyse non-equilibrium reactions and the patterns of activity for pyruvate kinase, phosphoenolpyruvate carboxykinase and malic enzyme are similar in the three organisms. The levels of tricarboxylic acid cycle intermediates inE.g.H., E.g.S. andE.m. are of the same order as those reported in tissues with an active cycle. Each has a complete sequence of cycle enzymes but there are substantial differences between the three parasites with regard to the activity of individual enzymes, The activities of NAD and NADP-linked isocitrate dehydrogenases are significantly lower inE.g.H. than inE.g.S. and particularly inE.m. which suggests that the tricarboxylic acid cycle may play a more important role in carbohydrate metabolism and energy production in the latter parasites. Nevertheless, the three organisms utilize fermentative pathways for alternative energy production, fix carbon dioxide via phosphoenolpyruvate carboxykinase and have a partial reversed tricarboxylic acid cycle. It is speculated thatin vivomore carbon will be channelled towards oxaloacetate than pyruvate at the phosphoenolpyruvate branch point. The steady state content of ATP and the ATP/AMP ratios are low in the three organisms, suggesting a low rate of ATP utilization in each.

scholarly journals Effect of renal tubule-specific knockdown of the Na+/H+exchanger NHE3 in Akita diabetic mice

2019 ◽  
Vol 317 (2) ◽  
pp. F419-F434 ◽  
Author(s):  
Akira Onishi ◽  
Yiling Fu ◽  
Manjula Darshi ◽  
Maria Crespo-Masip ◽  
Winnie Huang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Tricarboxylic Acid Cycle ◽  
Branched Chain Amino Acids ◽  
Tricarboxylic Acid ◽  
Proximal Tubules ◽  
Wild Type ◽  
Kidney Weight ◽  
Acid Cycle ◽  
Branched Chain

Na+/H+exchanger isoform 3 (NHE3) contributes to Na+/bicarbonate reabsorption and ammonium secretion in early proximal tubules. To determine its role in the diabetic kidney, type 1 diabetic Akita mice with tubular NHE3 knockdown [Pax8-Cre; NHE3-knockout (KO) mice] were generated. NHE3-KO mice had higher urine pH, more bicarbonaturia, and compensating increases in renal mRNA expression for genes associated with generation of ammonium, bicarbonate, and glucose (phosphoenolpyruvate carboxykinase) in proximal tubules and H+and ammonia secretion and glycolysis in distal tubules. This left blood pH and bicarbonate unaffected in nondiabetic and diabetic NHE3-KO versus wild-type mice but was associated with renal upregulation of proinflammatory markers. Higher renal phosphoenolpyruvate carboxykinase expression in NHE3-KO mice was associated with lower Na+-glucose cotransporter (SGLT)2 and higher SGLT1 expression, indicating a downward tubular shift in Na+and glucose reabsorption. NHE3-KO was associated with lesser kidney weight and glomerular filtration rate (GFR) independent of diabetes and prevented diabetes-associated albuminuria. NHE3-KO, however, did not attenuate hyperglycemia or prevent diabetes from increasing kidney weight and GFR. Higher renal gluconeogenesis may explain similar hyperglycemia despite lower SGLT2 expression and higher glucosuria in diabetic NHE3-KO versus wild-type mice; stronger SGLT1 engagement could have affected kidney weight and GFR responses. Chronic kidney disease in humans is associated with reduced urinary excretion of metabolites of branched-chain amino acids and the tricarboxylic acid cycle, a pattern mimicked in diabetic wild-type mice. This pattern was reversed in nondiabetic NHE3-KO mice, possibly reflecting branched-chain amino acids use for ammoniagenesis and tricarboxylic acid cycle upregulation to support formation of ammonia, bicarbonate, and glucose in proximal tubule. NHE3-KO, however, did not prevent the diabetes-induced urinary downregulation in these metabolites.

scholarly journals Role of Energy Metabolism in the Progression of Neuroblastoma

2021 ◽  
Vol 22 (21) ◽  
pp. 11421
Author(s):  
Monika Sakowicz-Burkiewicz ◽  
Tadeusz Pawełczyk ◽  
Marlena Zyśk
Keyword(s):  
Energy Metabolism ◽  
Extracellular Vesicles ◽  
Tricarboxylic Acid Cycle ◽  
Significant Risk ◽  
Metabolic Enzymes ◽  
Genetic Alterations ◽  
Tricarboxylic Acid ◽  
Primary Role ◽  
Acid Cycle ◽  
Risk Of Death

Neuroblastoma is a common childhood cancer possessing a significant risk of death. This solid tumor manifests variable clinical behaviors ranging from spontaneous regression to widespread metastatic disease. The lack of promising treatments calls for new research approaches which can enhance the understanding of the molecular background of neuroblastoma. The high proliferation of malignant neuroblastoma cells requires efficient energy metabolism. Thus, we focus our attention on energy pathways and their role in neuroblastoma tumorigenesis. Recent studies suggest that neuroblastoma-driven extracellular vesicles stimulate tumorigenesis inside the recipient cells. Furthermore, proteomic studies have demonstrated extracellular vesicles (EVs) to cargo metabolic enzymes needed to build up a fully operative energy metabolism network. The majority of EV-derived enzymes comes from glycolysis, while other metabolic enzymes have a fatty acid β-oxidation and tricarboxylic acid cycle origin. The previously mentioned glycolysis has been shown to play a primary role in neuroblastoma energy metabolism. Therefore, another way to modify the energy metabolism in neuroblastoma is linked with genetic alterations resulting in the decreased activity of some tricarboxylic acid cycle enzymes and enhanced glycolysis. This metabolic shift enables malignant cells to cope with increasing metabolic stress, nutrition breakdown and an upregulated proliferation ratio.

Ontogeny of pyruvate dehydrogenase complex and key enzymes involved in glycolysis and tricarboxylic acid cycle in rabbit fetal lung, heart, and liver

1990 ◽  
Vol 68 (10) ◽  
pp. 1210-1217 ◽  
Author(s):  
Bhagu R. Bhavnani ◽  
Duncan G. Wallace
Keyword(s):  
Pyruvate Kinase ◽  
Pyruvate Dehydrogenase ◽  
Fetal Liver ◽  
Tricarboxylic Acid Cycle ◽  
Pyruvate Dehydrogenase Complex ◽  
Fetal Lung ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Key Enzymes ◽  
Dehydrogenase Complex

The metabolic pathways by which the glycogen is utilized by fetal tissues is not well established. In the present study the ontogeny of seven key enzymes involved in glycolysis and the tricarboxylic acid cycle has been established for rabbit fetal lung, heart, and liver. In the fetal lung the activities of phosphofructokinase, pyruvate kinase, lactic dehydrogenase, citrate synthase, and malate dehydrogenase increase from day 21 to 25. Thereafter the levels either drop to day 19 levels or do not change. The isocitrate dehydrogenase activity continues to increase from day 19 of gestation to maximum level on day 31 of gestation. In fetal heart the pattern of activity is similar, but in fetal liver most of the enzymes reach maximum levels earlier and, with the exception of pyruvate kinase, do not show a significant fall in activity near term. The pattern of development of pyruvate dehydrogenase complex is different; maximum activity is observed on day 27 in fetal lung and heart and on day 21 in fetal liver. These results indicate that all three fetal tissues can oxidize glucose. Also, the accumulation of glycogen, particularly in fetal lung, appears to ensure that at specific times during gestation adequate quantities of energy (ATP) and substrates, required for surfactant phospholipid synthesis, are available independent of maternal supply of glucose or during brief episodes of hypoxia.Key words: glycogen, glycolysis, tricarboxylic acid cycle, pyruvate dehydrogenase, surfactant.

Effect of Ca2+ on cardiac mitochondrial energy production is modulated by Na+ and H+ dynamics

2007 ◽  
Vol 292 (6) ◽  
pp. C2004-C2020 ◽  
Author(s):  
My-Hanh T. Nguyen ◽  
S. J. Dudycha ◽  
M. Saleet Jafri
Keyword(s):  
Energy Metabolism ◽  
Energy Production ◽  
Hydrogen Exchange ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Calcium Dynamics ◽  
Mitochondrial Energy Metabolism ◽  
Acid Cycle ◽  
Atp Production ◽  
Sodium Hydrogen

The energy production of mitochondria in heart increases during exercise. Several works have suggested that calcium acts at multiple control points to activate net ATP production in what is termed “parallel activation”. To study this, a computational model of mitochondrial energy metabolism in the heart has been developed that integrates the Dudycha-Jafri model for the tricarboxylic acid cycle with the Magnus-Keizer model for mitochondrial energy metabolism and calcium dynamics. The model improves upon the previous formulation by including an updated formulation for calcium dynamics, and new descriptions of sodium, hydrogen, phosphate, and ATP balance. To this end, it incorporates new formulations for the calcium uniporter, sodium-calcium exchange, sodium-hydrogen exchange, the F1F0-ATPase, and potassium-hydrogen exchange. The model simulates a wide range of experimental data, including steady-state and simulated pacing protocols. The model suggests that calcium is a potent activator of net ATP production and that as pacing increases energy production due to calcium goes up almost linearly. Furthermore, it suggests that during an extramitochondrial calcium transient, calcium entry and extrusion cause a transient depolarization that serve to increase NADH production by the tricarboxylic acid cycle and NADH consumption by the respiration driven proton pumps. The model suggests that activation of the F1F0-ATPase by calcium is essential to increase ATP production. In mitochondria very close to the release sites, the depolarization is more severe causing a temporary loss of ATP production. However, due to the short duration of the depolarization the net ATP production is also increased.

scholarly journals Focally perfused succinate potentiates brain metabolism in head injury patients

2016 ◽  
Vol 37 (7) ◽  
pp. 2626-2638 ◽  
Author(s):  
Ibrahim Jalloh ◽  
Adel Helmy ◽  
Duncan J Howe ◽  
Richard J Shannon ◽  
Peter Grice ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Lactate Dehydrogenase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Cerebral Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Redox Status ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Pyruvate Ratio

Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high brain extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly with the mitochondrial electron transport chain, could improve cerebral metabolism. Microdialysis perfused disodium 2,3-13C2 succinate (12 mmol/L) for 24 h into nine sedated traumatic brain injury patients' brains, with simultaneous microdialysate collection for ISCUS analysis of energy metabolism biomarkers (nine patients) and nuclear magnetic resonance of 13C-labelled metabolites (six patients). Metabolites 2,3-13C2 malate and 2,3-13C2 glutamine indicated tricarboxylic acid cycle metabolism, and 2,3-13C2 lactate suggested tricarboxylic acid cycle spinout of pyruvate (by malic enzyme or phosphoenolpyruvate carboxykinase and pyruvate kinase), then lactate dehydrogenase-mediated conversion to lactate. Versus baseline, succinate perfusion significantly decreased lactate/pyruvate ratio (p = 0.015), mean difference −12%, due to increased pyruvate concentration (+17%); lactate changed little (−3%); concentrations decreased for glutamate (−43%) (p = 0.018) and glucose (−15%) (p = 0.038). Lower lactate/pyruvate ratio suggests better redox status: cytosolic NADH recycled to NAD+ by mitochondrial shuttles (malate-aspartate and/or glycerol 3-phosphate), diminishing lactate dehydrogenase-mediated pyruvate-to-lactate conversion, and lowering glutamate. Glucose decrease suggests improved utilisation. Direct tricarboxylic acid cycle supplementation with 2,3-13C2 succinate improved human traumatic brain injury brain chemistry, indicated by biomarkers and 13C-labelling patterns in metabolites.

scholarly journals Stimulation of [1-14C]oleate oxidation to 14CO2 in isolated rat hepatocytes by the catecholamines, vasopressin and angiotensin. A possible mechanism of action

1983 ◽  
Vol 212 (1) ◽  
pp. 85-91 ◽  
Author(s):  
M C Sugden ◽  
D I Watts
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Tricarboxylic Acid Cycle ◽  
Rat Hepatocytes ◽  
Tricarboxylic Acid ◽  
Isolated Rat Hepatocytes ◽  
Acid Cycle ◽  
14Co2 Production ◽  
Oxoglutarate Dehydrogenase ◽  
Stimulation Of

Adrenaline, noradrenaline, vasopressin and angiotensin increased 14CO2 production from [1-14C]oleate by hepatocytes from fed rats but not by hepatocytes from starved rats. The hormones did not increase 14CO2 production when hepatocytes from fed rats were depleted of glycogen in vitro. Increased 14CO2 production from]1-14C]oleate in response to the hormones was observed when hepatocytes from starved rats were incubated with 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase. 3-Mercaptopicolinate inhibited uptake and esterification of [1-14C]oleate, slightly increased 14CO2 production from [1-14C]oleate and greatly increased the [3-hydroxybutyrate]/[acetoacetate] ratio. In the presence of 3-mercaptopicolinate 14CO2 production in response to the catecholamines was blocked by the α-antagonist phentolamine and required extracellular Ca2+. The effects of vasopressin and angiotensin were also Ca2+-dependent. The actions of the hormones of 14CO2 production from [I-14C]oleate by hepatocytes from starved rats in the presence of 3-mercaptopicolinate thus have the characteristics of the response to the hormones found with hepatocytes from fed rats incubated without 3-mercaptopicolinate. The stimulatory effects of the hormones on 14CO2 production from [1-14C]oleate were not the result of decreased esterification (as the hormones increased esterification) or increased β-oxidation. It is suggested that the effect of the hormones to increase 14CO2 production from [1-14C]oleate are mediated by CA2+-activation of NAD+-linked isocitrate dehydrogenase, the 2-oxoglutarate dehydrogenase complex, and/or electron transport. The results also demonstrate that when the supply of oxaloacetate is limited it is utilized for gluconeogenesis rather than to maintain tricarboxylic acid-cycle flux.

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