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Glycolysis

About: Glycolysis is a research topic. Over the lifetime, 10593 publications have been published within this topic receiving 507460 citations. The topic is also known as: GO:0006096 & glycolysis.


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Journal ArticleDOI
01 Jul 2015-Oncogene
TL;DR: The multiple non-glycolytic roles of gly colytic enzymes, which are essential for promoting cancer cells' survival, proliferation, chemoresistance and dissemination, are outlined.
Abstract: Cancer cells enhance their glycolysis, producing lactate, even in the presence of oxygen. Glycolysis is a series of ten metabolic reactions catalysed by enzymes whose expression is most often increased in tumour cells. HKII and phosphoglucose isomerase (PGI) have mainly an antiapoptotic effect; PGI and glyceraldehyde-3-phosphate dehydrogenase activate survival pathways (Akt and so on); phosphofructokinase 1 and triose phosphate isomerase participate in cell cycle activation; aldolase promotes epithelial mesenchymal transition; PKM2 enhances various nuclear effects such as transcription, stabilisation and so on. This review outlines the multiple non-glycolytic roles of glycolytic enzymes, which are essential for promoting cancer cells' survival, proliferation, chemoresistance and dissemination.

161 citations

Journal ArticleDOI
TL;DR: In this paper, a mechanism of impaired glucose oxidation and enhanced aerobic glycolysis in pulmonary arterial hypertension (PAH) is discussed, which can be found in the Randle cycle.
Abstract: Mitochondria are central to cellular metabolism. The mitochondria’s metabolic pathways include fatty acid oxidation, glucose oxidation and glutaminolysis. The initial step in glucose metabolism occurs in the cytosol, where glycolysis converts glucose to pyruvate1 (Figure 1). Figure 1 Mechanism of impaired glucose oxidation and enhanced aerobic glycolysis in PAH. Changes in redox signaling, such as downregulation of SOD2 and the resultant decrease in H2O2 signaling, can activate transcription factors (i.e. HIF-1α) which in ... Normally, glycolysis is coupled to glucose oxidation, meaning that the pyruvate is transported into the mitochondria where it serves as a substrate for pyruvate dehydrogenase (PDH)3. Under pathologic conditions, such as inhibition of PDH, glycolysis may be uncoupled from glucose oxidation and remain a wholly cytosolic reaction that terminates in the generation of lactate. Metabolism is quite plastic and the relative importance of each pathway can change in response to environmental stimuli, such as substrate availability, the organism’s developmental stage, and pathologic stimuli, such as hypoxia, shear stress, pressure overload, ischemia and hypertrophy. In addition, the activity of one metabolic pathway alters the activity of competing pathways. Examples of this metabolic crosstalk include the reciprocal relationship between fatty acid and glucose oxidation. Fatty acid oxidation suppresses glucose oxidation, through a mechanism called the Randle cycle (Figure 2), named after Phillip Randle who first described the phenomenon3. Another example of metabolic plasticity is the uncoupling of glycolysis from glucose oxidation, so called aerobic glycolysis. Aerobic glycolysis is also called the Warburg effect, in honor of Otto Warburg who first described the phenomenon in cancer cells5. Warburg noted that this shift to glycolysis contributed to the growth and survival advantage of cancer cells5. He also observed, but could not explain, accumulation of ammonia in his cancer tissue culture. Ultimately this proved to relate to a concomitant upregulation of glutaminolysis in cancer cells. Aerobic glycolysis results in a reliance on glycolysis to produce ATP despite the presence of sufficient oxygen to have allowed pyruvate generation and mitochondrial glucose oxidation. Aerobic glycolysis usually reflects active inhibition of one or more mitochondrial enzymes, notably inhibition of PDH by pyruvate dehydrogenase kinases (PDK). These acquired changes in metabolism alter the cell’s bioenergetics status, susceptibility to hypertrophy and fibrosis, rates of proliferation and apoptosis, angiogenesis and contractility. Importantly, the cell’s metabolic choices can be pharmacologically manipulated, offering the potential for metabolic therapies. Figure 2 Manipulating fatty acid and glucose oxidation in PAH: The Randle’s cycle. Randle’s cycle is the reciprocal relationship between glucose oxidation and fatty acid oxidation. Note how the acetyl CoA and citrate produced by β-oxidation ... In addition to generating adenosine triphosphate (ATP), mitochondria are constantly dividing and joining together6. These highly conserved and regulated processes are called fission and fusion, respectively7. These non-canonical mitochondrial functions (fission, fusion), as well as migration, are called mitochondrial dynamics.8 Mitochondrial dynamics are important in physiology, participating in oxygen sensing9 and the distribution of mitochondria to daughter cells during mitosis10. Mitochondrial dynamics are also involved in cellular quality control, notably participating in mitophagy and apoptosis. Acquired and inherited disorders of mitochondrial dynamics are involved in diseases, including pulmonary arterial hypertension (PAH), cancer, and cardiac ischemia reperfusion injury7. Both metabolic plasticity and mitochondrial dynamics are relevant to the pathogenesis of PAH and offer new therapeutic targets in the pulmonary vasculature and the right ventricle.

161 citations

Journal ArticleDOI
TL;DR: An attempt to construct a reasonably complete and detailed model of the glycolytic and respiratory pathway of Ehrlich ascites cells which is in quantitative agreement with the available data, although this is probably not a unique representation of the data.

161 citations

Journal ArticleDOI
TL;DR: In NIDDM, marked hyperinsulinemia normalizes glycogen synthesis and total flux through glycolysis, but does not restore a normal distribution between oxidation and nonoxidative gly colysis; (d) hyperglycemia cannot overcome the defects in glucose oxidation andnonoxidatives; and (e) lipid oxidation is elevated and is suppressed only with hyperinsulininemia.
Abstract: Seven non-insulin-dependent diabetes mellitus (NIDDM) patients participated in three clamp studies performed with [3-3H]- and [U-14C]glucose and indirect calorimetry: study I, euglycemic (5.2 +/- 0.1 mM) insulin (269 +/- 39 pM) clamp; study II, hyperglycemic (14.9 +/- 1.2 mM) insulin (259 +/- 19 pM) clamp; study III, euglycemic (5.5 +/- 0.3 mM) hyperinsulinemic (1650 +/- 529 pM) clamp. Seven control subjects received a euglycemic (5.1 +/- 0.2 mM) insulin (258 +/- 24 pM) clamp. Glycolysis and glucose oxidation were quantitated from the rate of appearance of 3H2O and 14CO2; glycogen synthesis was calculated as the difference between body glucose disposal and glycolysis. In study I, glucose uptake was decreased by 54% in NIDDM vs. controls. Glycolysis, glycogen synthesis, and glucose oxidation were reduced in NIDDM patients (P < 0.05-0.001). Nonoxidative glycolysis and lipid oxidation were higher. In studies II and III, glucose uptake in NIDDM was equal to controls (40.7 +/- 2.1 and 40.7 +/- 1.7 mumol/min.kg fat-free mass, respectively). In study II, glycolysis, but not glucose oxidation, was normal (P < 0.01 vs. controls). Nonoxidative glycolysis remained higher (P < 0.05). Glycogen deposition increased (P < 0.05 vs. study I), and lipid oxidation remained higher (P < 0.01). In study III, hyperinsulinemia normalized glycogen formation, glycolysis, and lipid oxidation but did not normalize the elevated nonoxidative glycolysis or the decreased glucose oxidation. Lipid oxidation and glycolysis (r = -0.65; P < 0.01), and glucose oxidation (r = -0.75; P < 0.01) were inversely correlated. In conclusion, in NIDDM: (a) insulin resistance involves glycolysis, glycogen synthesis, and glucose oxidation; (b) hyperglycemia and hyperinsulinemia can normalize total body glucose uptake; (c) marked hyperinsulinemia normalizes glycogen synthesis and total flux through glycolysis, but does not restore a normal distribution between oxidation and nonoxidative glycolysis; (d) hyperglycemia cannot overcome the defects in glucose oxidation and nonoxidative glycolysis; (e) lipid oxidation is elevated and is suppressed only with hyperinsulinemia.

161 citations

01 Jan 2007
TL;DR: Despite different preferences for energy substrates and metabolic pathways between species, analysis of knockout mice revealed that glycolysis is indispensable for mouse sperm function and that oxidative phosphorylation is not essential for male fertility, suggesting that gly colysis could compensate for the lack of oxidative phosphate and recover most sperm function.
Abstract: Energy metabolism is a key factor supporting sperm function. Sustaining sperm motility and active protein modifications such as phosphorylation could be the reason why sperm require exceptionally more ATP than other cells. Many methods have been used to understand the relationship between energy metabolism and sperm function. These approaches have identified critical metabolic pathways that support specific processes during germ cell development and fertilisation. In round spermatids, lactate and pyruvate are the preferred substrates and the use of glucose is limited, however, during epididymal maturation sperm expand to use glycolysis. While the acrosome reaction requires lactate or pyruvate for ATP production by oxidative phosphorylation, gamete fusion requires glucose to produce NADPH by the pentose phosphate pathway. Sperm motility appears to be supported by relatively low ATP levels, but achievement of high ATP levels are essential for tyrosine phosphorylation linked to hyperactivation. Thus, each individual process and event requires a different substrate and metabolic pathway. Despite different preferences for energy substrates and metabolic pathways between species, analysis of knockout mice revealed that glycolysis is indispensable for mouse sperm function and that oxidative phosphorylation is not essential for male fertility. This suggests that glycolysis could compensate for the lack of oxidative phosphorylation and recover most sperm function. Spermatogenic cell-specific glycolytic enzymes may confer flexible use of substrates and adapt to unexpected conditions for substrates in the female reproductive tract.

161 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20231,429
20221,705
2021581
2020587
2019466
2018391