Energy Metabolism in Cortical Synaptic Terminals from Weanling and Mature Rat Brain: Evidence for Multiple Compartments of Tricarboxylic Acid Cycle Activity

1994 ◽  
Vol 16 (5-6) ◽  
pp. 291-300 ◽  
Author(s):  
Mary C. McKenna ◽  
J. Tyson Tildon ◽  
Joseph H. Stevenson ◽  
Irene B. Hopkins
Keyword(s):  
Energy Metabolism ◽  
Rat Brain ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Synaptic Terminals

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.

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 The regulation and glutamate metabolism by tricarboxylic acid-cycle activity in rat brain mitochondria

1978 ◽  
Vol 172 (1) ◽  
pp. 155-162 ◽  
Author(s):  
Steven C. Dennis ◽  
John B. Clark
Keyword(s):  
Rat Brain ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Brain Mitochondria ◽  
Inhibitory Effect ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Rat Brain Mitochondria ◽  
Fixed Concentration ◽  
K Concentration

1. The interrelationship of metabolism of pyruvate or 3-hydroxybutyrate and glutamate transamination in rat brain mitochondria was studied. 2. If brain mitochondria are incubated in the presence of equimolar concentrations of pyruvate and glutamate and the K+ concentration is increased from 1 to 20mm, the rate of pyruvate utilization is increased 3-fold, but the rate of production of aspartate and 2-oxoglutarate is decreased by half. 3. Brain mitochondria incubated in the presence of a fixed concentration of glutamate (0.87 or 8.7mm) but different concentrations of pyruvate (0 to 1mm) produce aspartate at rates that decrease as the pyruvate concentration is increased. At 1mm-pyruvate, the rate of aspartate production is decreased to 40% of that when zero pyruvate was present. 4. Brain mitochondria incubated in the presence of glutamate and malate alone produce 2-oxoglutarate at rates stoicheiometric with the rate of aspartate production. Both the 2-oxoglutarate and aspartate accumulate extramitochondrially. 5. Externally added 2-oxoglutarate has little inhibitory effect (Ki approx. 31mm) on the production of aspartate from glutamate by rat brain mitochondria. 6. It is concluded that the inhibitory effect of increased C2 flux into the tricarboxylic acid cycle on glutamate transamination is caused by competition for oxaloacetate between the transaminase and citrate synthase. 7. Evidence is provided from a reconstituted malate–aspartate (or Borst) cycle with brain mitochondria that increased C2 flux into the tricarboxylic acid cycle from pyruvate may inhibit the reoxidation of exogenous NADH. These results are discussed in the light of the relationship between glycolysis and reoxidation of cytosolic NADH by the Borst cycle and the requirement of the brain for a continuous supply of energy.

scholarly journals Bioenergetic Analysis of Single Pancreatic β-Cells Indicates an Impaired Metabolic Signature in Type 2 Diabetic Subjects

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3496-3503 ◽  
Author(s):  
Akos A. Gerencser
Keyword(s):  
Insulin Secretion ◽  
Membrane Potential ◽  
Energy Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Atp Synthesis ◽  
Tricarboxylic Acid ◽  
Β Cells ◽  
Acid Cycle ◽  
Type 2 Diabetic

Impaired activation of mitochondrial energy metabolism by glucose has been demonstrated in type 2 diabetic β-cells. The cause of this dysfunction is unknown. The aim of this study was to identify segments of energy metabolism with normal or with altered function in human type 2 diabetes mellitus. The mitochondrial membrane potential (ΔψM), and its response to glucose, is the main driver of mitochondrial ATP synthesis and is hence a central mediator of glucose-induced insulin secretion, but its quantitative determination in β-cells from human donors has not been attempted, due to limitations in assay technology. Here, novel fluorescence microscopic assays are exploited to quantify ΔψM and its response to glucose and other secretagogues in β-cells of dispersed pancreatic islet cells from 4 normal and 3 type 2 diabetic organ donors. Mitochondrial volume densities and the magnitude of ΔψM in low glucose were not consistently altered in diabetic β-cells. However, ΔψM was consistently less responsive to elevation of glucose concentration, whereas the decreased response was not observed with metabolizable secretagogue mixtures that feed directly into the tricarboxylic acid cycle. Single-cell analysis of the heterogeneous responses to metabolizable secretagogues indicated no dysfunction in relaying ΔψM hyperpolarization to plasma membrane potential depolarization in diabetic β-cells. ΔψM of diabetic β-cells was distinctly responsive to acute inhibition of ATP synthesis during glucose stimulation. It is concluded that the mechanistic deficit in glucose-induced insulin secretion and mitochondrial hyperpolarization of diabetic human β-cells is located upstream of the tricarboxylic acid cycle and manifests in dampening the control of ΔψM by glucose metabolism.

scholarly journals Integrative Analysis of Multiomics Data Identified Acetylation as Key Variable of Excessive Energy Metabolism in Hyperthyroidism-induced Osteoporosis Rats

2021 ◽  
Author(s):  
Jiaxin Bei ◽  
Shaoping Zhu ◽  
Minqun Du ◽  
Zheng Tang ◽  
Cailing Chen ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Bone Loss ◽  
Previous Experiment ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Creb Binding Protein ◽  
Acid Cycle ◽  
Metabolism Enzymes ◽  
Close Relationship

Abstract Background The results from the previous experiment have demonstrated that there were occurrence of bone loss and excess metabolism in Hyperthyroidism-induced rats. Thus, there was speculation that there may be an underlying relationship between metabolism and bone loss. In addition, there were past studies showing acetylation influencing metabolism in tissues and diseases. The hypothesis from this case study stated that excessive metabolism was induced upon acetylated vital metabolism enzymes. Results In the case study, a HYP-induced osteoporosis rats model was used and the glucose metabolite was tested through the acetylation of proteins by the mass spectrometer. The results showed that pivotal enzymes of Glycolysis-Tricarboxylic acid cycle-Oxidative phosphorylation were acetyled along with upregulated metabolites. All the acetyly-lysine sites of related enzymes were listed in this article.Our results showed that bone loss in HYP rats accompanied by upregulation of CREB-binding protein (Crebbp, CBP). Furthermore, our result indicated that CBP has a close relationship with enhancement of LDHa that promote glucose metabolism. Conclusions Acetylation is the key variable of energy metabolism in hyperthyroid osteoporosis rats, therein, we showed a representation relationship between CBP and LDHa.

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.

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