Antihyperglycemic Potential of Back Tea Extract Attenuates Tricarboxylic Acid Cycle Enzymes by Modulating Carbohydrate Metabolic Enzymes in Streptozotocin-Induced Diabetic Rats

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.

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Analysis of glucose metabolism in diabetic rat retinas

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00323.2005 ◽

2006 ◽

Vol 290 (6) ◽

pp. E1057-E1067 ◽

Cited By ~ 57

Author(s):

M. Shamsul Ola ◽

Deborah A. Berkich ◽

Yuping Xu ◽

M. Todd King ◽

Thomas W. Gardner ◽

...

Keyword(s):

Oxidative Stress ◽

Glucose Metabolism ◽

Tricarboxylic Acid Cycle ◽

Lactate Production ◽

Tricarboxylic Acid ◽

Diabetic Rats ◽

Glycolytic Flux ◽

Acid Cycle

This study was conceived in an effort to understand cause and effect relationships between hyperglycemia and diabetic retinopathy. Numerous studies show that hyperglycemia leads to oxidative stress in the diabetic retinas, but the mechanisms that generate oxidative stress have not been resolved. Increased electron pressure on the mitochondrial electron transfer chain, increased generation of cytosolic NADH, and decreases in cellular NADPH have all been cited as possible sources of reactive oxygen species and nitrous oxide. In the present study, excised retinas from control and diabetic rats were exposed to euglycemic and hyperglycemic conditions. Using a microwave irradiation quenching technique to study retinas of diabetic rats in vivo, glucose, glucose-derived metabolites, and NADH oxidation/reduction status were measured. Studying excised retinas in vitro, glycolytic flux, lactate production, and tricarboxylic acid cycle flux were evaluated. Enzymatically assayed glucose 6-phosphate and fructose 6-phosphate were only slightly elevated by hyperglycemia and/or diabetes, but polyols were increased dramatically. Cytosolic NADH-to-NAD ratios were not elevated by hyperglycemia nor by diabetes in vivo or in vitro. Tricarboxylic acid cycle flux was not increased by the diabetic state nor by hyperglycemia. On the other hand, small increases in glycolytic flux were observed with hyperglycemia, but glycolytic flux was always lower in diabetic compared with control animals. An observed decrease in activity of glyceraldehyde-3-phosphate dehydrogenase may be partially responsible for slow glycolytic flux for retinas of diabetic rats. Therefore, it is concluded that glucose metabolism, downstream of hexokinase, is not elevated by hyperglycemia or diabetes. Metabolites upstream of glucose such as the sorbitol pathway (which decreases NADPH) and polyol synthesis are increased.

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Analysis of tricarboxylic acid cycle intermediates in dried blood spots by ultra-performance liquid chromatography-tandem mass spectrometry

Journal of Biochemical and Clinical Genetics ◽

10.24911/jbcgenetics/183-1563341940 ◽

2019 ◽

pp. 1

Author(s):

Lamia Dirbashi

Keyword(s):

Mass Spectrometry ◽

Tricarboxylic Acid Cycle ◽

Dried Blood Spots ◽

Ultra Performance Liquid Chromatography ◽

Tricarboxylic Acid ◽

Tandem Mass ◽

Acid Cycle ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass ◽

Tricarboxylic Acid Cycle Intermediates

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Faculty Opinions recommendation of Crosstalk between the tricarboxylic acid cycle and peptidoglycan synthesis in Caulobacter crescentus through the homeostatic control of α-ketoglutarate.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.729075299.793537174 ◽

2017 ◽

Author(s):

Kevin D Young ◽

Matthew Jorgenson

Keyword(s):

Caulobacter Crescentus ◽

Tricarboxylic Acid Cycle ◽

Tricarboxylic Acid ◽

Homeostatic Control ◽

Acid Cycle ◽

Peptidoglycan Synthesis

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Modulation of tricarboxylic acid cycle dehydrogenases during hepatocarcinogenesis induced by hexachlorocyclohexane in mice

Experimental and Toxicologic Pathology ◽

10.1016/j.etp.2008.09.004 ◽

2009 ◽

Vol 61 (4) ◽

pp. 325-332 ◽

Cited By ~ 9

Author(s):

Devendra Kumar Bhatt ◽

Mehajbeen Bano

Keyword(s):

Tricarboxylic Acid Cycle ◽

Tricarboxylic Acid ◽

Acid Cycle

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Effects of sevoflurane anesthesia and abdominal surgery on the systemic metabolome: a prospective observational study

BMC Anesthesiology ◽

10.1186/s12871-021-01301-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yiyong Wei ◽

Donghang Zhang ◽

Jin Liu ◽

Mengchan Ou ◽

Peng Liang ◽

...

Keyword(s):

Abdominal Surgery ◽

General Anesthesia ◽

Tricarboxylic Acid Cycle ◽

Tricarboxylic Acid ◽

Metabolic Changes ◽

Sevoflurane Anesthesia ◽

Glutamate Metabolism ◽

Acid Cycle ◽

Link Type ◽

The Mean

Abstract Background Metabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear, which might contribute to postoperative outcomes. Methods Five hundred patients who underwent abdominal surgery were included. General anesthesia was mainly maintained with sevoflurane. The end-tidal sevoflurane concentration (ETsevo) was adjusted to maintain BIS (Bispectral index) value between 40 and 60. The mean ETsevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. The patients were further divided into low ETsevo group (mean − SD) and high ETsevo group (mean + SD) to investigate the possible metabolic changes relevant to the amount of sevoflurane exposure. Results The mean ETsevo of the 500 patients was 1.60% ± 0.34%. Patients with low ETsevo (n = 55) and high ETsevo (n = 59) were selected for metabolomic analysis (1.06% ± 0.13% vs. 2.17% ± 0.16%, P < 0.001). Sevoflurane and abdominal surgery disturbed the tricarboxylic acid cycle as identified by increased citrate and cis-aconitate levels and impacted glycometabolism as identified by increased sucrose and D-glucose levels in these 114 patients. Glutamate metabolism was also impacted by sevoflurane and abdominal surgery in all the patients. In the patients with high ETsevo, levels of L-glutamine, pyroglutamic acid, sphinganine and L-selenocysteine after sevoflurane anesthesia and abdominal surgery were significantly higher than those of the patients with low ETsevo, suggesting that these metabolic changes might be relevant to the amount of sevoflurane exposure. Conclusions Sevoflurane anesthesia and abdominal surgery can impact principal metabolic pathways in clinical patients including tricarboxylic acid cycle, glycometabolism and glutamate metabolism. This study may provide a resource data for future studies about metabolism relevant to general anaesthesia and surgeries. Trial registration www.chictr.org.cn. identifier: ChiCTR1800014327.

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