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Bioenergetics
Published in Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan, Strength and Conditioning in Sports, 2023
Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan
Although blood glucose is preferentially used, slow glycolysis can use either blood glucose or muscle glycogen as an energy source. Aerobic or slow glycolysis is a result of mitochondria activity being sufficient to accept the two NADH produced during glycolysis (Pasteur effect (161, 187) (Figure 2.5). An additional six ATP can be created resulting from the entrance of the two NADH into the electron transport system. During slow (aerobic) glycolysis, pyruvate can enter the mitochondrial matrix via a localized carrier mechanism in the outer and inner membranes (35, 51, 186). Two proteins are believed to be involved in pyruvate mitochondrial transport, mitochondrial pyruvate carriers MPC1 and MPC2 form a hetero-oligomeric complex in the inner mitochondrial membrane to facilitate pyruvate transport (186). In this manner, pyruvate can lose a carboxyl group (as CO2) and be made available for oxidation.
Features of Lipid Metabolism in Diabetes Mellitus and Ischemic Heart Disease
Published in E.I. Sokolov, Obesity and Diabetes Mellitus, 2020
The relation between the glucose level in the blood and the absorption of glucose by the myocardium was studied by many authors, mainly experimentally. It was found under clinical conditions that glucose is used in glycolysis for supporting anaerobic metabolism. It was proved experimentally that the rate of absorption of glucose by the cardiac myocytes from the extracellular space is limited by the rate of tissue transportation of glucose through a cell membrane. There is a clear relation between the rate of transportation and that of absorption of glucose under the influence of insulin, and also under conditions of hypoxia. Much attention in the experiments was devoted to studying glycolysis, i.e. the decomposition of glucose and glycogen in the myocardium, when lactate forms under anaerobic conditions. In normal oxidative metabolism, glycolysis results in the formation of pyruvate, which under aerobic conditions decomposes in the Krebs cycle. Under anaerobic conditions, glycolysis is the only source of ATP. In the absence of oxygen, the rate of glycolysis grows several times owing to the Pasteur effect. In deciphering the biochemical essence of the Pasteur effect, we can say that it consists in an increase in the rate of lactate formation under anaerobic conditions. When an animal inhales a hypoxic mixture, the rate of glucose absorption grows, and instead of the absorption of lactate by the myocardium (which occurs under normal conditions), the emergence of lactate from the cardiac myocytes is observed.
Oxygen Supply to Malignant Tumors
Published in Hans-Inge Peterson, Tumor Blood Circulation: Angiogenesis, Vascular Morphology and Blood Flow of Experimental and Human Tumors, 2020
The Pasteur effect is usually defined as the inhibition of glycolysis by oxygen in tissues showing both the aerobic and anaerobic pathway of glucose breakdown. In the presence of O2 , glycolysis is restricted in favor of the oxidative pathway. Since the aerobic pathway is the most economic and effective way to utilize glucose, the glucose consumption by the cell can generally be limited if there has been no previous absolute or relative glucose deficiency. In vivo investigations on the inoculated DS-Carcinosarcoma in the rat kidney also show a typical Pasteur effect when the conditions are changed from arterial normoxemia to respiratory hyperoxia. Following an increase in the arterial O2 partial pressure from 89 to 480 mmHg, a drop in glycolytic rate by about 10% is observed although the improved O2 supply benefits only the first quarter of the area adjacent to a capillary i.e., the arterial end of the capillary. The release of lactate from the tumor tissue into the blood is reduced as a consequence of the diminished glycolytic rate; the lactate-pyruvate ratio drops correspondingly.98 However, no significant reduction of the glucose uptake was observed. A decrease in the glucose uptake could not be expected under these conditions because of a deficient glucose supply to the tumor cell in vivo.
Lipidomic analysis of cancer cells cultivated at acidic pH reveals phospholipid fatty acids remodelling associated with transcriptional reprogramming
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Lorena Urbanelli, Sandra Buratta, Mariantonia Logozzi, Nico Mitro, Krizia Sagini, Rossella Di Raimo, Donatella Caruso, Stefano Fais, Carla Emiliani
A well-recognised and common metabolic phenotype observed in most types of solid tumours is the elevated rate of fermentative glycolysis, i.e. the non-oxidative conversion of glucose to lactic acid. While this can be induced as an adaptive response to poor oxygenation (the “Pasteur Effect”), a remarkable century old observation is that this glycolytic phenotype can be hardwired, and thus cancers ferment glucose even in the presence of adequate oxygen (the “Warburg Effect”). Although the mechanism and drivers of glycolytic switch are still debated9,10, it is an unequivocal fact that tumours are characterised by the accumulation of H+ in their microenvironment leading to its acidification, with values as low as pH 6.511–14. This acidic microenvironment strongly influences cancer progression and evolution12. Although it is initiated early in carcinogenesis, it is retained as cancers become locally invasive, a process known as “niche engineering”. As acidity is evident in early cancers, it could possibly contribute to intratumoral genetic heterogeneity or even to a sort of microevolutionary process12,15.
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
There are numerous molecular modulators of glycolytic flux, the most well-known of which was discovered in 1860 by Louis Pasteur [3]. Pasteur showed that oxygen inhibits fermentation and that glucose consumption is inversely proportional to oxygen availability (the Pasteur effect). It is now clear that the allosteric properties of 6-Phosphofructo-1-kinase (PFK-1) can account for most aspects of the Pasteur’s effect [4]. Many tumors have high rates of glycolysis regardless of oxygen availability (the Warburg effect). These tumors depend largely on the glycolytic pathway for the generation of ATP and biomolecules to meet most of their energy demand. Warburg attributed this metabolic alteration to mitochondrial ‘respiration injury’ and considered this the most fundamental metabolic change in malignant transformation or ‘the origin of cancer cells’ [1]. However, this hypothesis was neglected because some tumors do not have defects in respiration; besides, respiration also exerts a regulatory effect on glycolysis [5]. Although some cancer cells do not show high glycolytic activity [6], the Warburg effect has been consistently observed in a wide range of human cancers and forms the physiological basis for the use of positron emission tomography (PET) scans in clinical oncology [7]. There are likely to be several biochemical and molecular mechanisms underlying the Warburg effect, including mitochondrial dysfunction [8,9], oncogenic alterations, leading to increased glycolysis [10,11], as well as adaptive responses to the tumor microenvironment [12,13].
Metformin induces myeloma cells necrosis and apoptosis and it is considered for therapeutic use
Published in Journal of Chemotherapy, 2023
Zhentian Wu, Lianghua Wu, Liangliang Zou, Muqing Wang, Xin Liu
Similarly, a previous study in acute myelocytic leukemia (AML) cell lines indicated that metformin inhibits cell proliferation in U937, HL60 and MOLM14 cells, molecular mechanisms for the effect on AML cells, however, also differ from cell line to cell line. For HL-60 and MOLM14 cells, it induces apoptosis with cell cycle arrest at S-G2/M phage, for U937 cells, it doesn’t induce apoptosis, the cell cycle is arrested at the G0/G1 phase [27]. Further study demonstrates that the different react to metformin is mediated by the capability to elicit the Pasteur effect [27]. How metformin regulates the viability of different myeloma cells need further elucidate.