Maturation of Brain ATP Metabolism
Richard A. Jonas, Jane W. Newburger, Joseph J. Volpe, John W. Kirklin in Brain Injury and Pediatric Cardiac Surgery, 2019
It has long been recognised that brain ATP metabolism must be studied in situ with intact cerebral blood flow (CBF), substrate transport, functioning interneuronal connections, and the interdependence of ATP utilization and synthesis.9 Higher rates of aerobic glycolysis are measured in the intact brain than in vitro. In vitro measures of the effects of pre-mortem conditions always are plagued by the uncertain assumption that postmortem changes do not alter morphologic and biochemical characteristics present at the time of sacrifice. These methodological weaknesses are avoided by noninvasive in situ measurement and imaging of brain ATP metabolic systems. The electroencephalogram (EEG) may provide an index of gross changes in ATP use during high energy demand (e.g., seizures) and energy deficit (e.g., hypoxia) states.7,28 Regional measurements of glucose and oxygen consumption and of blood flow are possible using nonmetabolized, radio-labelled physiological analogues in animal and human studies.9,29–31 These studies, including PET, provide localization of brain function because of the close coupling of large changes in localized ATP metabolism and CBF to physiological events.9,31
Nanomaterials for Theranostics: Recent Advances and Future Challenges *
Valerio Voliani in Nanomaterials and Neoplasms, 2021
In addition to the original and revised hallmarks described by Hanahan and Weinberg [29, 30], Luo and Elledge outlined the stress phenotypes of cancer, i.e., DNA damage/replication stress, proteotoxic stress, mitotic stress, metabolic stress, and oxidative stress [36]. For example, production of reactive oxygen species (ROS) is the defining characteristic of oxidative stress in cancer. ROS have been regarded as very sensitive stimuli while designing activatable nanotheranostic platforms [218, 219]. Moreover, ROS are highly linked to endogenous DNA damage events in cancer cells. Aerobic glycolysis, which is used for extensive proliferation, enables tumor cells to acidify their microenvironment (metabolic stress), leading to the escape from immune surveillance [164–168, 171]. Therefore, the acidic microenvironment of cancer cells provides excellent opportunities to optimally design multifunctional nanoplatforms for theranostic applications.
Principles of oncology
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
Blood flow in tumours is often sporadic and unreliable. As a result, cancer cells may have to spend prolonged periods starved of oxygen – in a state of relative hypoxia. Compared with the corresponding normal cells, some cancer cells may be better able to survive in hypoxic conditions. This ability may enable tumours to grow and develop despite an impoverished blood supply. Cancer cells can alter their metabolism even when oxygen is abundant; they break down glucose but do not, as normal cells would do, send the resulting pyruvate to the mitochondria for conversion, in an oxygen-dependent process, to carbon dioxide. This is the phenomenon of aerobic glycolysis, or the Warburg effect, and leads to the production of lactate. In an act of symbiosis, lactate-producing cancer cells may provide lactate for adjacent cancer cells which are then able to use it, via the citric acid cycle, for energy production. This cooperation is similar to that which occurs in skeletal muscle during exercise.
The potential utility of PFKFB3 as a therapeutic target
Published in Expert Opinion on Therapeutic Targets, 2018
Ramon Bartrons, Ana Rodríguez-García, Helga Simon-Molas, Esther Castaño, Anna Manzano, Àurea Navarro-Sabaté
Some of the earliest modern studies on cancer observed abnormalities in tumor metabolism. In the pioneering studies of the 1920s, Otto Warburg observed that cancers possessed a remarkable ability to sustain high rates of anaerobic glycolysis even in the presence of oxygen [1]. Anaerobic glycolysis uses glucose to produce lactate, while aerobic glycolysis (respiration) produces pyruvate for the tricarboxylic acid cycle and generates energy via oxidative phosphorylation. An essential thermodynamic trade-off exists between these two pathways with respect to the rate (moles of adenosine triphosphate (ATP) per unit of time) and yield (moles of ATP per mole of substrate), with fermentation occurring approximately 100 times faster than respiration, although yielding roughly 18-fold less ATP per mole of glucose. Population biology modeling has demonstrated how organisms use the intrinsic trade-off between these two pathways to maximal effect. Cells with a higher rate, but lower yield of ATP production, may gain a selective advantage when competing for shared energy resources [2].
Glycometabolic rearrangements–aerobic glycolysis in pancreatic ductal adenocarcinoma (PDAC): roles, regulatory networks, and therapeutic potential
Published in Expert Opinion on Therapeutic Targets, 2021
Aerobic glycolysis has roles not only in matching energy requirements of cellular activities but also in facilitating invasion and metastasis by participating in complex mechanisms, including the following. (1) Upregulation of aerobic glycolysis promotes the epithelial–mesenchymal transition phenotype of PDAC cells by maintaining low levels of ROS, which enables dissemination of epithelial cells [76]. (2) In the hypoxic tumor microenvironment, aerobic glycolysis acts on PDAC cells and endothelial cells; this synergetic action promotes tumor angiogenesis and provides a basis for PDAC metastasis [61,77]. (3) The acidic tumor microenvironment resulting from the high rate of glycolysis promotes the escape of tumor cells from immune surveillance and increases the possibility of metastasis [78–81]. (4) Aerobic glycolysis also occurs in tumor-associated macrophages (TAMs) and favors metastatic colonization of PDAC cells [82]. In conclusion, aerobic glycolysis is involved in the whole metastasis process of PDAC, including its origin, pathways, and endpoints. In-depth studies of the details of these mechanisms would be beneficial to exploring new ways to overcome the malignancy of PDAC.
TKP, a Serine Protease from Trichosanthes kirilowii, Inhibits Cell Proliferation by Blocking Aerobic Glycolysis in Hepatocellular Carcinoma Cells
Published in Nutrition and Cancer, 2022
Aerobic glycolysis is defined as the seventh major feature of the tumor (31). Tumor cells mainly depend on aerobic glycolysis to gain energy. Even in the presence of oxygen, cancer cells prefer to consume higher amounts of glucose and convert glucose into lactate instead of performing oxidative phosphorylation (32). Aerobic glycolysis is crucial for cancer cell proliferation. Aerobic glycolysis provides cancer cells with energy and metabolic intermediates for inducing the rapid proliferation of cancer cells (17, 18). The present study indicated that TKP treatment significantly decreased the cell viability and colony formation rate of Bel-7402 and HepG2 cells, suggesting that TKP inhibits the proliferation of Bel-7402 and HepG2 cells. Moreover, we found that TKP markedly suppressed aerobic glycolysis, which was characterized by depressed glucose uptake, lactate production and the expression of aerobic glycolysis-related proteins including GLUT1, PDK, and LDHA. These results suggested that aerobic glycolysis is pivotal for TKP-induced inhibitory effects on the proliferation of Bel-7402 and HepG2 cells.
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