GLYCOLYSIS Student Edition 5/30/13 version Dr. Brad Chazotte 213 Maddox Hall [email protected] Web Site: http://www.campbell.edu/faculty/chazotte Original material only ©2000-14 B. Chazotte Pharm. 304 Biochemistry Fall 2014 Goals •Learn the enzymes and sequence of reactions in glycolysis •Develop an understanding of the chemical logic of the glycolysis pathway •Understand the basis and need for redox balance in glycolysis •Learn and understand the control(s) and control points of the glycolysis pathway. •Learn where products of glycolysis can go. •Be aware that other sugars can enter the glycolysis pathway Glycolysis: An Energy Conversion Pathway Used by Many Organisms •Almost a universal central pathway for glucose catabolism •The chemistry of these reactions has been completely conserved. •Glycolysis differs among species only in its regulation and in the metabolic fate of the pyruvate generated. •In eukaryotic cells glycolysis takes place in the cell cytosol. The ...
TY - JOUR. T1 - Inhibition of glyceraldehyde-3-phosphate dehydrogenase and other glycolytic enzymes by acrylamide. AU - Sabri, M. I.. AU - Spencer, P. S.. PY - 1980/1/1. Y1 - 1980/1/1. UR - http://www.scopus.com/inward/record.url?scp=0018932962&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0018932962&partnerID=8YFLogxK. M3 - Article. AN - SCOPUS:0018932962. VL - 19. SP - S455. JO - Neuroscience Letters. JF - Neuroscience Letters. SN - 0304-3940. IS - SUPPL. 5. ER - ...
Autophagy occurs in cells that undergoing nutrient deprivation. Glycolysis rapidly supplies energy for the proliferation of cancer cells. Cardamonin inhibits proliferation and enhances autophagy by mTORC1 suppression in ovarian cancer cells. Here, we investigate the relationship between cardamonin-triggered autophagy and glycolysis inhibition via mTORC1 suppression. Treated with indicated compounds, ATP content and the activity of hexokinase (HK) and lactate dehydrogenase (LDH) were analyzed by the assay kits. Autophagy was detected by monodansylcadaverin (MDC) staining. The relationship between cardamonin-triggered autophagy and glycolysis inhibition via mTORC1 suppression was analyzed by Western blot. We found that cardamonin inhibited the lactate secretion, ATP production, and the activity of HK and LDH. The results demonstrated that cardamonin enhanced autophagy in SKOV3 cells, as indicated by acidic compartments accumulation, microtubule-associated protein 1 Light Chain 3-II (LC3-II) and lysosome
Title: The Warburg Effect: Why and How Do Cancer Cells Activate Glycolysis in the Presence of Oxygen?. VOLUME: 8 ISSUE: 3. Author(s):Miguel Lopez-Lazaro. Affiliation:Department of Pharmacology,Faculty of Pharmacy, C/ Profesor Garcia Gonzalez, 41012 Sevilla, Spain.. Keywords:Aerobic glycolysis, glycolysis inhibitors, metabolism, dysoxic metabolism, hypoxia-inducible factor 1, reactive oxygen species, hydrogen peroxide, superoxide anion. Abstract: Cells can obtain energy through the oxygen-dependent pathway of oxidative phosphorylation (OXPHOS) and through the oxygen-independent pathway of glycolysis. Since OXPHOS is more efficient in generating ATP than glycolysis, it is recognized that the presence of oxygen results in the activation of OXPHOS and the inhibition of glycolysis (Pasteur effect). However, it has been known for many years that cancer cells and non-malignant proliferating cells can activate glycolysis in the presence of adequate oxygen levels (aerobic glycolysis or Warburg effect). ...
The reconstituted glycolytic system described previously (Scopes, 1973) was used to simulate post-mortem glycolytic metabolism in muscle. The effects of the following factors have been investigated: ATPase (adenosine triphosphatase) amount, AMP deaminase amount, percentage of the phosphorylase in the a form and the effect of diluting the glycolytic enzyme complex as a whole. It was confirmed that the rate of metabolism was solely dependent on the amount of ATPase present and that various concentrations of the glycolytic enzymes had no effect over a wide range encompassing the variation found in anatomically different muscles. The extent of metabolism, represented by the value of the ultimate pH, depended markedly on the amount of phosphorylase in the a form; as little as 1% of the a form resulted in a considerably lower pH than in its absence. To a lesser extent the amount of AMP deaminase also affected the ultimate pH, but this was probably only significant for comparisons of genetically ...
Posts about K. The ingredients of antineoplaston AS2-1 down-regulate glycolysis pathways in glioblastoma cells. Neuro-Oncology 2008; 10:1148″ written by didymusjudasthomas
Red blood cells require glycolysis as their sole source of ATP in order to survive, because they do not have mitochondria. Glycolysis can be either: Aerobic (requiring oxygen ) - The pyruvate produced by this process can undergo further oxidation via the citric acid cycle. How many net ATP are produced as a result of glycolysis? The citric acid cycle initiates with (a) succinic acid (b) pyruvic acid (c) acetyl coenzyme A (d) fumaric acid Answer: (c) acetyl coenzyme A 3. Although oxygen is present, it is not required for glycolysis to occur. Therefore, oxygen would not always be needed. a) Glycolysis requires the use of 9 different enzymes to occur. About glycolysis, which statement is FALSE? Which of the following is a waste product from amino acid catabolism? Therefore, the mitochondria is not required. O2 is not required for glycolysis. What is the final electron acceptor in the electron transport chain? At this step, glycolysis has reached the break-even point: 2 molecules of ATP were ...
Glycolysis simply means the breakdown (lysis) of glucose and consists of a series of chemical reactions that are controlled by enzymes. How does glycolysis produce ATP? Important Facts about Glycolysis (cont. Glycolysis Inhibitors Upregulation of glycolysis with increase in glucose consumption for metabolic pathways to generate ATP is the universal property of all the cancers and tumors. 1 ATP, 3 NADH, and 1 FADH2 2 ATPs and 2 NADH 3 NADH and 1 FADH2 4 ATPs, 6 NADH, and 2 FADH2 Newtons second law states that force is equal to mass times acceleration: F = ma. Im aware that ultimately in the human body, after sugar is converted into pyruvate, then if fermentation happens it will be converted into lactate, or if aerobic respiration happens then it wont. ATP is created directly from glycolysis through the process of substrate-level phosphorylation (SLP) and indirectly by oxidative phosporylation (OP). Does Glycolysis produce lactate, or pyruvate? Something as complicated as cellular respiration ...
The notes are very useful indeed. Although the term is often taken to be synonymous with the Embden-Meyerhof-Parnas (EMP) pathway, other glycolytic pathways exist, among them the Entner-Doudoroff pathway that proceeds via a gluconic acid intermediate and a complex set … Glycolysis Questions and Answers. It occures in practically all life as we know it and its all about taking glucose as a fuel and, in the process of breaking it up, lycing the glucose, glycolysis, breaking it up into two pyruvate molecules. What are the functions of glycolysis? In the first step of glycolysis, the glucose is initiated or primed for the subsequent steps by phosphorylation at the C. The process involves the transfer of phosphate from the ATP to glucose forming Glucose-6-phosphate in the presence of the enzyme hexokinase and glucokinase (in animals and microbes). Glycolysis is defined as an enzymatic breakdown of carbohydrates (as glucose) by way of phosphate derivatives with the production of pyruvic or lactic ...
Most normal cells in the presence of oxygen utilize glucose for mitochondrial oxidative phosphorylation. In contrast, many cancer cells rapidly convert glucose to lactate in the cytosol, a process termed aerobic glycolysis. This glycolytic phenotype is enabled by lactate dehydrogenase (LDH), which catalyzes the inter-conversion of pyruvate and lactate. The purpose of this study was to identify and characterize potent and selective inhibitors of LDHA. High throughput screening and lead optimization were used to generate inhibitors of LDHA enzymatic activity. Effects of these inhibitors on metabolism were evaluated using cell-based lactate production, oxygen consumption, and 13C NMR spectroscopy assays. Changes in comprehensive metabolic profile, cell proliferation, and apoptosis were assessed upon compound treatment. 3-((3-carbamoyl-7-(3,5-dimethylisoxazol-4-yl)-6-methoxyquinolin-4-yl) amino) benzoic acid was identified as an NADH-competitive LDHA inhibitor. Lead optimization yielded molecules with LDHA
1. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis?. Nat Rev Cancer. 2004;4:891-9 2. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11:85-95 3. Chen W, Wang Q, Bai L. et al. RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1alpha-mediated mitochondrial oxidative phosphorylation and glycolysis. Cell Death Differ. 2014;21:1061-70 4. Sebastian C, Zwaans BM, Silberman DM. et al. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell. 2012;151:1185-99 5. Mathupala SP, Rempel A, Pedersen PL. Aberrant glycolytic metabolism of cancer cells: a remarkable coordination of genetic, transcriptional, post-translational, and mutational events that lead to a critical role for type II hexokinase. J Bioenerg Biomembr. 1997;29:339-43 6. Levine AJ, Puzio-Kuter AM. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 2010;330:1340-4 7. Pelicano H, Martin ...
Fingerprint Dive into the research topics of Hyperpermeability and ATP depletion induced by chronic hypoxia or glycolytic inhibition in Caco-2BBe monolayers. Together they form a unique fingerprint. ...
Glycolysis is a central pathway for the production of energy. In eukaryotic systems, it breaks down a supply of glucose into substrates for the production of fat, amino acids and ATP. The pathway of glycolysis is important in a number of contexts. It is required for the production of cellular energy, involved in the generation of fat and regulation of glucose levels. Yeast glycolysis is used in the industrial production of ethanol and the art of wine making.. The pages here are designed to provide information needed to model the glycolytic pathway. To model any process requires a good understanding of the components of the system, the interactions between those components in the form of reactions, and the kinetics (temporal behavior) of the components/reactions. To understand and interpret the results of the model requires an understanding of the experimental system. A good understanding of the systems behavior allows us to compare the simulation results to real world data. Glycolysis has ...
The experiments reported in the present study were designed to determine which glycolytic enzymes are associated with SR from skeletal and cardiac muscle and whether the ATP generated from these glycolytic reactions can support the SR Ca2+-ATPase and 45Ca pumping into the SR. Our results indicate that the entire chain of glycolytic enzymes from aldolase onward, including aldolase, GAPDH, PGK, phosphoglyceromutase, enolase, and pyruvate kinase are bound to SR membranes in cardiac and skeletal muscle as evidenced by the ability of glycolytic substrates and cofactors (without ATP) to support 45Ca transport. IAA, an inhibitor of GAPDH, eliminated SR 45Ca transport supported by FDP (the substrate for aldolase), but transport was completely restored by PEP, indicating that both of the ATP-producing glycolytic enzymes, GAPDH/PGK and pyruvate kinase, were associated with the SR and functionally capable of providing ATP for the Ca2+ pump. Addition of a soluble hexokinase ATP trap eliminated 45Ca ...
Glycolysis is the process of converting glucose into two molecules of pyruvate acid by producing ATP and NADH. Since the glycolysis cycle involves the conversion of blood sugar into an anion of pyruvic acid (pyruvate), glycolysis is also referred to as the citric acid cycle. Most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates. Glycolysis consists of an energy-requiring phase followed by an energy-releasing phase. To use Khan Academy you need to upgrade to another web browser. However, in order for this energy to be utilized by organisms, this molecule needs to be degraded via glycolysis, which is a common metabolic pathway for all living beings, where partial decomposition of these molecules occur in the presence or absence of oxygen. Donate or volunteer today! Glycolysis is the process of breaking down glucose. Gratuit. Through two distinct phases, the six-carbon ring of glucose is cleaved into two three-carbon sugars of pyruvate through a series of
GLYCOLYSIS Glycolysis is the first stage of cellular respiration. It is a process of breakdown of glucose into pyruvic acid. Scientist Embden, Meyerhof, & Parnas described different steps of glycolysis. So glycolysis also called EMP pathway. PLACE OF GLYCOLYSIS Glycolysis occurs in cytoplasm. SUBSTRATE Glucose REQUIREMENTS One molecule of glucose. 2ATP. 4ADP. 2NAD. Inorganic phosphate. […]. ...
GLYCOLYSIS Glycolysis is the first stage of cellular respiration. It is a process of breakdown of glucose into pyruvic acid. Scientist Embden, Meyerhof, & Parnas described different steps of glycolysis. So glycolysis also called EMP pathway. PLACE OF GLYCOLYSIS Glycolysis occurs in cytoplasm. SUBSTRATE Glucose REQUIREMENTS One molecule of glucose. 2ATP. 4ADP. 2NAD. Inorganic phosphate. […]. ...
Review. 1826 (2), 370-84. Dec 2012. Dysregulation of Glucose Transport, Glycolysis, TCA Cycle and Glutaminolysis by Oncogenes and Tumor Suppressors in Cancer Cells. Jin-Qiang Chen 1, Jose Russo. PMID: 22750268. DOI: 10.1016/j.bbcan.2012.06.004. Abstract. A common set of functional characteristics of cancer cells is that cancer cells consume a large amount of glucose, maintain high rate of glycolysis and convert a majority of glucose into lactic acid even in the presence of oxygen compared to that of normal cells (Warburgs Effects). In addition, cancer cells exhibit substantial alterations in several energy metabolism pathways including glucose transport, tricarboxylic acid (TCA) cycle, glutaminolysis, mitochondrial respiratory chain oxidative phosphorylation and pentose phosphate pathway (PPP). In the present work, we focused on reviewing the current knowledge about the dysregulation of the proteins/enzymes involved in the key regulatory steps of glucose transport, glycolysis, TCA cycle and ...
Glycolysis is the principal route for carbohydrate metabolism. The ability of glycolysis to provide ATP in the absence of oxygen is especially important, because this allows skeletal muscle to perform at very high levels of work output when oxygen supply is insufficient, and it allows tissues to survive anoxic episodes. However, heart muscle, which is adapted for aerobic performance, has relatively low glycolytic activity and poor survival under conditions of ischemia. Diseases in which enzymes of glycolysis (eg, pyruvate kinase) are deficient are mainly seen as hemolytic anemias or, if the defect affects skeletal muscle (eg, phosphofructokinase), as fatigue. In fast-growing cancer cells, glycolysis proceeds at a high rate, forming large amounts of pyruvate, which is reduced to lactate and exported. This produces a relatively acidic local environment in the tumor, which may have implications for cancer therapy. The lactate is used for gluconeogenesis in the liver (Chapter 19), an ...
A key hallmark of cancer cells is their capacity to metabolize glucose at an elevated rate (1, 2). Critical to this highly glycolytic phenotype is the first enzymatic step of glycolysis, catalyzed by hexokinase (HK), during which glucose is phosphorylated and thereby trapped within the cell. There are four HK enzymes in mammals, HK1, HK2, HK3, and glucokinase (GCK), which are structurally similar but expressed in a tissue- specific manner (3). Remarkably, only HK2 is overexpressed in cancer cells (4) and contributes to the high glycolytic rate in tumors (5). Given the selective expression of HK2 in cancer, Patra and colleagues (6) investigated whether targeting this particular glycolytic enzyme could be used for cancer therapy.. Several previous studies have reported that inhibition of HK2 can block cancer cell survival. Depletion of HK2 with short hairpin RNA (shRNA) inhibited tumor growth in a xenograft model of glioblastoma multiforme (7). Moreover, HK2 mRNA and protein levels were found to ...
We present a model of osmoadaptation in S.cerevisiae based on existing experimental and theoretical work. In order to investigate the impact of osmoadaptation on glycolysis, this model focuses on the interactions between glycolysis and osmoadaptation, namely the production of glycerol and its influence on flux towards pyruvate. Evaluation of this model shows that, depending on initial relations between glycerol and pyruvate production, the increased glycerol production can have a substantial negative effect on the pyruvate production rate. Existing experimental data and a detailed analysis of the model lead to the suggestion of an interaction between activated Hog1 and activators of glycolysis such as Pfk26.
Glycolysis is the process of converting glucose into pyruvate and generating small amounts of ATP (energy) and NADH (reducing power). It is a central pathway that produces important precursor metabolites: six-carbon compounds of glucose-6P and fructose-6P and three-carbon compounds of glycerone-P, glyceraldehyde-3P, glycerate-3P, phosphoenolpyruvate, and pyruvate [MD:M00001]. Acetyl-CoA, another important precursor metabolite, is produced by oxidative decarboxylation of pyruvate [MD:M00307]. When the enzyme genes of this pathway are examined in completely sequenced genomes, the reaction steps of three-carbon compounds from glycerone-P to pyruvate form a conserved core module [MD:M00002], which is found in almost all organisms and which sometimes contains operon structures in bacterial genomes. Gluconeogenesis is a synthesis pathway of glucose from noncarbohydrate precursors. It is essentially a reversal of glycolysis with minor variations of alternative paths [MD:M00003 ...
Glycolysis is the process of converting glucose into pyruvate and generating small amounts of ATP (energy) and NADH (reducing power). It is a central pathway that produces important precursor metabolites: six-carbon compounds of glucose-6P and fructose-6P and three-carbon compounds of glycerone-P, glyceraldehyde-3P, glycerate-3P, phosphoenolpyruvate, and pyruvate [MD:M00001]. Acetyl-CoA, another important precursor metabolite, is produced by oxidative decarboxylation of pyruvate [MD:M00307]. When the enzyme genes of this pathway are examined in completely sequenced genomes, the reaction steps of three-carbon compounds from glycerone-P to pyruvate form a conserved core module [MD:M00002], which is found in almost all organisms and which sometimes contains operon structures in bacterial genomes. Gluconeogenesis is a synthesis pathway of glucose from noncarbohydrate precursors. It is essentially a reversal of glycolysis with minor variations of alternative paths [MD:M00003 ...
Glycolysis is the principal pathway of glucose metabolism occurs in the cytoplasm of all cells where glucose is oxidized to pyruvate (in aerobic condition) or lactate (in anaerobic condition) and generates energy in the form of ATP. Types of glycolysis pathway: Glycolysis pathways are two types; Aerobic glycolysis - Aerobic glycolysis occurs in cells with mitochondria and in the presence .... Read More » ...
TY - JOUR. T1 - Pyruvate kinase M2. T2 - Multiple faces for conferring benefits on cancer cells. AU - Tamada, Mayumi. AU - Suematsu, Makoto. AU - Saya, Hideyuki. PY - 2012/10/15. Y1 - 2012/10/15. N2 - The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species.PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced ...
TY - JOUR. T1 - Pyruvate kinase M2. T2 - Multiple faces for conferring benefits on cancer cells. AU - Tamada, Mayumi. AU - Suematsu, Makoto. AU - Saya, Hideyuki. PY - 2012/10/15. Y1 - 2012/10/15. N2 - The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species.PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced ...
The activities of ATP-consuming and ATP-producing steps of the Embden-Meyerhof pathway, as well as other glycolytic enzymes (phosphoglucomutase and enolase) and glucose-6-phosphate dehydrogenase are lower in leucocytes from cord blood than in white cells from adults. These results are related to previous observations (reduced anaerobic glycolysis and nitroblue tetrazolium-test in leucocytes from newborn infants) and discussed in connection with the fact that newborn infants are more susceptible to infections than normal adults.
The addition of glucose to Saccharomyces cerevisiae cells causes reprogramming of gene expression. Glucose is sensed by membrane receptors as well as (so far elusive) intracellular sensing mechanisms. The availability of four yeast strains that display different hexose uptake capacities allowed us to study glucose-induced effects at different glycolytic rates. Rapid glucose responses were observed in all strains able to take up glucose, consistent with intracellular sensing. The degree of long-term responses, however, clearly correlated with the glycolytic rate: glucose-stimulated expression of genes encoding enzymes of the lower part of glycolysis showed an almost linear correlation with the glycolytic rate, while expression levels of genes encoding gluconeogenic enzymes and invertase (SUC2) showed an inverse correlation. Glucose control of SUC2 expression is mediated by the Snf1-Mig1 pathway. Mig1 dephosphorylation upon glucose addition is known to lead to repression of target genes. Mig1 was
Upon liver injury, hepatic stellate cells (HSCs) transdifferentiate to migratory, proliferative and extracellular matrix-producing myofibroblasts (e.g., activated HSCs; aHSCs) causing liver fibrosis. HSC activation is associated with increased glycolysis and glutaminolysis. Here, we compared the contribution of glycolysis, glutaminolysis and mitochondrial oxidative phosphorylation (OXPHOS) in rat and human HSC activation. Basal levels of glycolysis (extracellular acidification rate ~3-fold higher) and particularly mitochondrial respiration (oxygen consumption rate ~5-fold higher) were significantly increased in rat aHSCs, when compared to quiescent rat HSC. This was accompanied by extensive mitochondrial fusion in rat and human aHSCs, which occurred without increasing mitochondrial DNA content and electron transport chain (ETC) components. Inhibition of glycolysis (by 2-deoxy-D-glucose) and glutaminolysis (by CB-839) did not inhibit rat aHSC proliferation, but did reduce Acta2 (encoding α-SMA) ...
Reprogramming glycolysis for directing glycolytic metabolites to a specific metabolic pathway is expected to be useful for increasing microbial production of certain metabolites, such as amino acids, lipids or considerable secondary metabolites. In this report, a strategy of increasing glycolysis by altering the metabolism of inositol pyrophosphates (IPs) for improving the production of S-adenosyl-l-methionine (SAM) for diverse pharmaceutical applications in yeast is presented. The genes associated with the metabolism of IPs, arg82, ipk1 and kcs1, were deleted, respectively, in the yeast strain Saccharomyces cerevisiae CGMCC 2842. It was observed that the deletions of kcs1 and arg82 increased SAM by 83.3 % and 31.8 %, respectively, compared to that of the control. In addition to the improved transcription levels of various glycolytic genes and activities of the relative enzymes, the levels of glycolytic intermediates and ATP were also enhanced. To further confirm the feasibility, the kcs1 was deleted in
Most cancer cells use aerobic glycolysis to fuel their growth. The enzyme lactate dehydrogenase-A (LDH-A) is key to cancers glycolytic phenotype, catalysing the regeneration of nicotinamide adenine dinucleotide (NAD þ ) from reduced nicotinamide adenine dinucleotide (NADH) necessary to sustain glycolysis. As such, LDH-A is a promising target for anticancer therapy. Here we ask if the tumour suppressor p53, a major regulator of cellular metabolism, influences the response of cancer cells to LDH-A suppression. LDH-A knockdown by RNA interference (RNAi) induced cancer cell death in p53 wild-type, mutant and p53-null human cancer cell lines, indicating that endogenous LDH-A promotes cancer cell survival irrespective of cancer cell p53 status. Unexpectedly,however,weuncoveredanovelroleforp53intheregulationofcancercellNADþ anditsreducedformNADH.Thus, LDH-A silencing by RNAi, or its inhibition using a small-molecule inhibitor, resulted in a p53-dependent increase in the cancer cell ...
This article is Part 2 of a 3 part series that outlines the three basic energy systems used in sport, their interactions with one another, and how to train each one. Below the Introduction (technical explanation), we offer 7 sessions (in 3 stages) for training the Glycolytic System. Introduction Glycolysis literally means the breakdown (lysis) of glucose and consists of a series of enzymatic reactions. The carbohydrates we eat supply the body with glucose, which can be stored as glycogen in the muscles or liver for later use. The end product of glycolysis is pyruvic acid. Pyruvic acid can then be either funneled through a process called the Krebs cycle (see the Oxidative System in next weeks article) or converted into lactic acid (lactate + hydrogen ion). Traditionally, if the final product was lactic acid, the process was labelled anaerobic glycolysis and if the final product remained as pyruvate the process was labelled aerobic glycolysis. Oxygen availability only determines the fate of the end
Inflammaging is a condition of chronic low-grade inflammation due to the aging process and is associated with a variety of chronic diseases. Monocytes are innate immune cells which contribute to inflammation and are dysregulated during aging, demonstrated reduced phagocytosis, increased inflammation, and alterations in subset proportions. Metabolism is known to determine immune cell function, with quiescent and anti-inflammatory cells primarily relying on fatty acid oxidation, while activated and inflammatory cells primarily rely on glycolysis. We have previously shown an age-related decrease in mitochondrial respiratory capacity in monocytes, so we hypothesized here that a compensatory shift toward glycolysis would occur which would also exacerbate inflammation. Using Seahorse assays, we profiled glycolysis in classical monocytes isolated from older (60-80 yr) and younger (18-35 yr) adults. Aging did not affect parameters of basal glycolysis in the glycolysis stress test, nor did it alter glycolytic
Scientists think that glycolysis evolved before the other stages of cellular respiration. This is because the other stages need oxygen, whereas glycolysis does not, and there was no oxygen in Earths atmosphere when life first evolved about 3.5 to 4 billion years ago. Cellular respiration that proceeds without oxygen is called anaerobic respiration. Then, about 2 or 3 billion years ago, oxygen was gradually added to the atmosphere by early photosynthetic bacteria. After that, living things could use oxygen to break down glucose and make ATP. Today, most organisms make ATP with oxygen. They follow glycolysis with the Krebs cycle and electron transport to make more ATP than by glycolysis alone. Cellular respiration that proceeds in the presence of oxygen is called aerobic respiration.. ...
Numerous laboratories have shown that hyperglycemia increases cerebral ischemic damage. This presumably results from increased lactate production and accumulation during ischemia. Although increased tissue lactic acidosis is associated with increased ischemic brain damage, this damage has not been directly linked to glycolytic flux. Because 2-deoxyglucose (2-DG) is a competitive inhibitor of glycolysis we tested its ability to reduce hyperglycemia-exacerbated ischemic brain damage. Severe forebrain ischemia was produced by the four-vessel occlusion model in rats. Four rats received 3 g/kg glucose and saline while a second group (n = 5) was injected with 3 g/kg glucose plus 1.6 g/kg 2-DG. A third group (n = 5) was treated with 1 g/kg glucose plus saline and a fourth group (n = 5) received 1 g/kg glucose and 1.6 g/kg 2-DG. All rats were injected i.p. 10 minutes prior to the ischemic insult with the same volume/kg body weight. All rats receiving the high dose of glucose alone (3 g/kg) were dead ...
Purpose: The hypermetabolic nature of cancer cells, especially their increased reliance on aerobic glycolysis which has been associated with more aggressive phenotype, is considered metabolic hallmarks of cancer cells including oral squamous cell carcinoma (OSCC) cells. However, its precise mechanisms remain unknown. Cylindromatosis (CYLD) is recognized as a tumor suppressor gene whereas little is available about its impact on cancer progression. Our unpublished data showed that lower CYLD expression was associated with poor prognosis in OSCC patients. The objective of our study was to address specific contributions of CYLD to the signature metabolic features of OSCC cells.. Materials and methods: We determined the level of glucose consumption as well as lactate production to evaluate the effects of CYLD knockdown by siRNA on aerobic glycolysis in human OSCC cell lines. In addition, we measured extracellular acidification and oxygen consumption rates in OSCC cells by using XF Extracellular Flux ...
How cellular respiration can be sped up or slowed down. The free energy released in this process is used as ATP and NADP. Glucose-6-phosphate is isomerised to fructose-6-phosphate by phosphohexose isomerase. Stimulation of glycolysis by placing tubers in an atmosphere of nitrogen led to significant declines in their contents of fructose-6-phosphate and phosphoenolpyruvate. In the fifth step, an isomerase transforms the dihydroxyacetone-phosphate into its isomer, glyceraldehyde-3-phosphate. The fourth step in glycolysis employs an enzyme, aldolase, to cleave 1,6-bisphosphate into two three-carbon isomers: dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate. How many steps are in glycolysis and what are they? The glycolytic pathway is a major metabolic pathway for microbial fermentation which involves the catabolism of glucose into pyruvate. Steps 1 and 3 = - 2ATP Steps 7 and 10 = + 4 ATP Net visible ATP produced = 2. 4. Only three steps produce a large decrease in free energy, meaning ...
Yeast glycolytic oscillations have been studied since the 1950s in cell-free extracts and intact cells. For intact cells, sustained oscillations have so far only been observed at the population level, i.e. for synchronized cultures at high biomass concentrations. Using optical tweezers to position yeast cells in a microfluidic chamber, we were able to observe sustained oscillations in individual isolated cells. Using a detailed kinetic model for the cellular reactions, we simulated the heterogeneity in the response of the individual cells, assuming small differences in a single internal parameter. This is the first time that sustained limit-cycle oscillations have been demonstrated in isolated yeast cells. © 2012 FEBS.. ...
This study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting. BackgroundDuring the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples.ResultsSurprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2
Resistance to anti-cancer therapies is a consequence of adaptation of cancer cells but also of maladaptation of tumor-infiltrating immune cells. The opposing roles acquired by the immune system have to be faced in order to fight tumor growth and therapy resistance. Effector immune cells are recruited and activated but they are blocked by the strong immunosuppressive nature of the tumor microenvironment (TME). Immune evasion and deregulation of energy metabolism are two hallmarks of cancer that may be functionally linked. Malignant cells which present a high glycolytic phenotype, besides creating metabolic demanding environments that encroach on the function of tumor-infiltrating immune cells, also release immunosuppressive metabolites and by-products, such as lactate, forming a metabolic symbiosis with immune cells. This acidic TME has a strong impact in the profile of tumor-infiltrating immune cells, being instrumental for immunosuppression. Therefore, in this review, we focus on key molecular
Solution for question: Distinguish Between Glycolysis and Citric Acid Cycle concept: Glycolysis. For the courses CBSE (Arts), CBSE (Commerce), CBSE (Science)
One of the most distinctive features of cancer metabolism is the increased uptake of glucose and amino acids compared to that in quiescent normal cells (Pavlova and Thompson, 2016). Glucose in cancer cells is then predominantly metabolized by aerobic glycolysis rather than by oxidative metabolism. The significance of upregulated glycolysis in cancer cells has been highlighted as a critical metabolic hub to interconnect with other metabolic pathways (Fig. 6), including (1) the pentose phosphate pathway (PPP) to generate pentose phosphates for ribonucleotide synthesis and NADPH, (2) the hexosamine pathway to synthesize UDP-N-acetylglucosamine for protein glycosylation, and (3) the serine biosynthesis pathway coupled with the one-carbon cycle to produce SAM and NADPH (Hay, 2016). Thus, cells with upregulated glucose uptake increase the flux to these branching pathways and thereby modulate the cellular levels of their intermediary metabolites.. The increased flux of glycolysis may exceed the ...
Endogenous nitric oxide (NO) acts on cytochrome c oxidase, the terminal enzyme in the mitochondrial electron transport chain, inhibiting mitochondrial oxygen consumption and promoting the release of free radicals. Quintero et al. investigated the consequences of NO regulation of mitochondrial activity in vascular endothelial cells, which are highly glycolytic and have abundant NO. Analysis of the effects of inhibitors of mitochondrial electron transport or glycolysis at various oxygen concentrations indicated that ATP production in human umbilical vein endothelial cells (HUVECs) depended more on glycolysis than it did on mitochondrial respiration. Exposure to a low concentration of oxygen (1.5%) that promoted the accumulation of hypoxia-inducible factor 1α (HIF-1α) in human smooth muscle and epithelial kidney cells had little effect on HIF-1α abundance in human vascular endothelial cells unless the production of NO was inhibited. The ability of NO to inhibit HIF-1α accumulation in HUVECs ...
Temperature strongly affects microbial growth, and many microorganisms have to deal with temperature fluctuations in their natural environment. To understand regulation strategies that underlie microbial temperature responses and adaptation, we studied glycolytic pathway kinetics in Saccharomyces cerevisiae during temperature changes. Saccharomyces cerevisiae was grown under different temperature regimes and glucose availability conditions. These included glucose-excess batch cultures at different temperatures and glucose-limited chemostat cultures, subjected to fast linear temperature shifts and circadian sinoidal temperature cycles. An observed temperature-independent relation between intracellular levels of glycolytic metabolites and residual glucose concentration for all experimental conditions revealed that it is the substrate availability rather than temperature that determines intracellular metabolite profiles. This observation corresponded with predictions generated in silico with a kinetic
To test the effectiveness of dichloroacetate, a known Pyruvate Dehydrogenase Kinase inhibitor, as a method of slowing down the proliferation of cancerous cells as well as forcing them from aerobic glycolysis towards oxidative phosphorylation as their main energy source.
The composition of the extracellular matrix (ECM) of skeletal muscle fibers is a unique environment that supports the regenerative capacity of satellite cells; the resident stem cell population. The impact of environment has great bearing on key properties permitting satellite cells to carry out tissue repair. In this study, we have investigated the influence of the ECM and glycolytic metabolism on satellite cell emergence and migration-two early processes required for muscle repair. Our results show that both influence the rate at which satellite cells emerge from the sub-basal lamina position and their rate of migration. These studies highlight the necessity of performing analysis of satellite behavior on their native substrate and will inform on the production of artificial scaffolds intended for medical uses.
BioAssay Systems Glycolysis Assay Kit (ECGL-100) is based on the production of L-Lactate from glycolysis in cells. The intensity of the reduced dye at 565 nm is proportional to the L-lactate concentration which in turn is proportional to the glycolytic rate of cells. Detection range up to 10 mM L-lactate.
Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Due to differential regulation of enzymatic activities, PKM2 but not PKM1 has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL. Depletion of PKM2 at the time of c-MYC over-expression in murine livers did not affect c-MYC induced tumorigenesis and resulted in liver tumor formation with decreased pyruvate kinase activity and decreased catabolism of glucose into alanine and the Krebs cycle. An increased PKM1/PKM2 ratio by ectopic PKM1 expression further decreased ...
Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter. This FAO shift increased the protoporphyrin IX prosthetic group of indoleamine 2,3-dioxgenase-1 (IDO) while suppressing interleukin(IL)-6 and IL-12 cytokine expression, culminating in enhanced IDO activity and the generation of regulatory T cells. We demonstrated that blockade of this pathway augmented anti-melanoma immunity, enhanced the activity of anti-PD-1 antibody immunotherapy, and suppressed disease progression ...
Metabolic heterogeneity between neoplastic cells and surrounding stroma has been described in several epithelial malignancies; however, the metabolic phenotypes of neoplastic lymphocytes and neighboring stroma in diffuse large B-cell lymphoma (DLBCL) is unknown. We investigated the metabolic phenotypes of human DLBCL tumors by using immunohistochemical markers of glycolytic and mitochondrial oxidative phosphorylation (OXPHOS) metabolism. The lactate importer MCT4 is a marker of glycolysis, whereas the lactate importer MCT1 and TOMM20 are markers of OXPHOS metabolism. Staining patterns were assessed in 33 DLBCL samples as well as 18 control samples (non-neoplastic lymph nodes). TOMM20 and MCT1 were highly expressed in neoplastic lymphocytes, indicating an OXPHOS phenotype, whereas non-neoplastic lymphocytes in the control samples did not express these markers. Stromal cells in DLBCL samples strongly expressed MCT4, displaying a glycolytic phenotype, a feature not seen in stromal elements of non
The effects of xenon, argon, and hydrogen on the aerobic and anaerobic metabolism of mouse liver, brain, and sarcoma slices have been investigated. Xenon was found to alter the rates of metabolism of these tissues in a manner almost identical with helium. The gas increased the rate of oxygen consumption in all three tissues and significantly depressed that of anaerobic glycolysis in brain and liver. The depression of glycolysis in sarcoma was less pronounced and not highly significant.. Although both the magnitude and statistical significance of the effects observed with argon were much smaller, there was a seeming adherence to the general pattern established by xenon and helium. Hydrogen while remaining essentially ineffective insofar as oxygen uptake was concerned, depressed glycolysis in both liver and brain slices but did not significantly affect sarcoma slices.. The following points are stressed in the Discussion: (1) the magnitude and direction of effects exerted by helium, argon, xenon, ...
The addition of glucose to tps1Δ cells of the yeast S. cerevisiae causes hyperaccumulation of all glycolytic metabolites upstream and depletion of all metabolites downstream of GAPDH, suggesting that the deletion of Tps1 in some way creates a bottleneck in glycolysis at the level of GAPDH (27). Measurements of the specific activity of the glycolytic enzymes in cell extracts as well as determination of initial glucose uptake rates did not reveal significant differences between the wild-type and tps1 strains that could explain the glycolytic bottleneck in tps1Δ cells (1, 11). More detailed measurements of the glucose uptake rate and the pH dependency of GAPDH in the present work have underscored the conclusion that there is no difference in the inherent activity of these two crucial components in the tps1Δ strain. Hence, the bottleneck appears to be due to a metabolic or regulatory problem at the level of GAPDH that is not maintained in cell extracts and is not apparent from the Vmax or Km of ...
In Arabidopsis thaliana, enzymes of glycolysis are present on the surface of mitochondria and free in the cytosol. The functional significance of this dual localization has now been established by demonstrating that the extent of mitochondrial association is dependent on respiration rate in both Arabidopsis cells and potato (Solanum tuberosum) tubers. Thus, inhibition of respiration with KCN led to a proportional decrease in the degree of association, whereas stimulation of respiration by uncoupling, tissue ageing, or overexpression of invertase led to increased mitochondrial association. In all treatments, the total activity of the glycolytic enzymes in the cell was unaltered, indicating that the existing pools of each enzyme repartitioned between the cytosol and the mitochondria. Isotope dilution experiments on isolated mitochondria, using (13)C nuclear magnetic resonance spectroscopy to monitor the impact of unlabeled glycolytic intermediates on the production of downstream intermediates derived from
A response to Leprince: The role of Bergmann glial cells in cerebellar development. Cancer & Metabolism 2013, 1:14. We recently demonstrated that developmentally regulated aerobic glycolysis is integral to the normal process of postnatal neurogenesis and becomes co-opted in medulloblastoma. In our work, we concluded that Hexokinase 2 (Hk2), which we found to be required for Shh-induced aerobic glycolysis, was expressed specifically by cerebellar granule neuron progenitors (CGNPs). We observed altered migration of CGNPs in hGFAP-cre;Hk2f/f mice and attributed this aspect of the phenotype to premature differentiation of CGNPs caused by loss of aerobic glycolysis. In response to our work, LePrince draws attention to the role of Bergmann glia in cerebellar development.. LePrince raises the important point that cerebellar granule neurons (CGNPs) do not develop in isolation but rather interact critically with the Bergmann glia. The Bergmann glia establish a radial scaffold on which the CGNPs migrate ...
Fig. 5 MAGE-A genes promote resistance to a glycolysis inhibitor in human cancer and mouse spermatogonia stem cells.. (A) Expression of human MAGE-A6 in MIA PaCa-2 cancer cells in complete media or treated with 2 mM 2-DG for 4 days. (B and C) Human MAGE-A6 expression promotes sustained growth of MIA PaCa-2 cancer cells treated with 2 mM 2-DG glycolysis inhibitor (B), but not without (C). (D) Mage-a Δ8 SSCs are more sensitive to 2-DG than littermate control wild-type SSCs. Cells were treated with indicated doses of 2-DG for 16 hours in the absence of feeder cells before the percentage of live cells was determined by annexin-V/4′,6-diamidino-2-phenylindole staining and flow cytometry analysis. (E and F) Metabolomic analysis of MAGE-A6 expressing MIA PaCa-2 cells grown in standard media or 2 mM 2-DG for 2 to 10 days. Nontargeted metabolomics was performed by the National Institutes of Health (NIH) West Coast Metabolomics Core (n = 6). Principal components analysis (E) and relative quantities of ...
View Notes - Ch_9_Glycolysis_Fermentation from BIO 3 at Evergreen Valley. Glycolysis and Fermentation Biol-003 A. Introduction 1. Chemotroph vs. autotroph 2. - G = free energy change a. - G favorable
The tumor suppressor BRCA1 regulates the DNA damage response (DDR) and other processes that remain incompletely defined. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal E3 ligase activity. Here, it is demonstrated that BRCA1 promotes oxidative metabolism by degrading Oct1 (POU2F1), a transcription factor with proglycolytic and tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells toward a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype. RNA sequencing (RNAseq) confirms deregulation of metabolic genes downstream of Oct1. BRCA1 mediates Oct1 ubiquitylation and degradation, and mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1-mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not perturb growth in standard culture, but inhibits growth in soft agar and xenograft assays. In primary breast cancer clinical specimens, Oct1 ...
Introduction: Induced pluripotent stem cells (iPSC) can be sources for cells such as megakaryocytes (MK) that cannot be obtained easily from humans. Studies have shown that iPSC depend more on glycolysis for energy production than their somatic sources. Less is known about metabolic processes in cells differentiated from iPSC, and no studies exist for derived MK.. Hypothesis: MKs differ in glycolysis gene expression from parent iPSC.. Methods: We compared mRNA expression for glycolytic enzyme genes in 14 human iPSC lines paired with derived MK lines. Transcript abundance levels were determined in RNA-Seq data using the TopHat/Cufflinks software suite. Transcript data was filtered such that the interquartile range over the dataset was , 1 FPKM, and levels were transformed as log2(FPKM+1). MK:iPS expression ratios for genes encoding 11 glycolytic enzymes (Figure) were estimated using multilevel mixed model regression, wherein multiple transcripts were nested within a gene, and iPS/MK pairing was ...
Preclinical imaging with radiolabeled probes became an integral part of the complex translational process that moves a newly developed compound from laboratory to clinical application. Imaging studies in animal tumor models may be undertaken to test a newly synthesized tracer, a newly developed drug or to interrogate, in the living organism, specific molecular and biological processes underlying tumor growth and progression. The aim of the present review is to outline the current knowledge and future perspectives of preclinical imaging in oncology by providing examples from recent literature. Among the biological processes and molecular targets that can be visualized with radiolabeled probes in animal tumor models, we focused on proliferation, expression of targets suitable for therapy, glycolytic phenotype, metastatic dissemination, tumor angiogenesis and survival. The major contribution of preclinical imaging emerging from these studies is the development and validation of imaging biomarkers ...
1. With reference to the post-operative dysfunction of the liver observed after halothane anaesthesia, the effects of the anaesthetic on some metabolic functions were studied in the isolated perfused rat liver. Oxygen uptake, glycolysis, gluconeogenesis and urea synthesis were affected by halothane at a concentration (2.5% of the gas phase) within the range used in clinical anaesthesia. 2. At this concentration of halothane uptake of oxygen was inhibited in livers from both fed and starved rats. 3. In livers from fed rats there was a 16-fold increase in lactate production. This was accompanied by a fivefold decrease in the tissue content of 2-oxoglutarate and a more than twofold decrease in citrate. The calculated [free NAD+]/[free NADH] ratio in both cytoplasm and mitochondria was lower in the halothane-exposed livers than in controls. 4. In livers of starved rats the rate of gluconeogenesis from lactate was decreased by halothane to 30% of the control rate. 5. Halothane inhibited ...
Bommer, Guido. Protecting Glycolysis and the Pentose Phosphate Pathway from Metabolic Side-Products.Keystone Conference: Novel Frontiers in Understanding Tumor Metabolism (Banff, Canada, du 21/02/2016 au 25/02/2016 ...
Cancer cell metabolism is reprogrammed to sustain the high metabolic demands of cell proliferation. Recently, emerging studies have shown that mitochondrial metabolism is a potential target for cancer therapy. Herein, four mitochondria-targeted phosphorescent cyclometalated iridium(iii) complexes have been d
Ok, so its well established that a level of mechanical tension is needed in order to maximise the hypertrophic responses to resistance training. But what about metabolic stress? Well, it has been suggested that metabolic stress might play an additive role by enhancing the post exercise hypertrophic response (Schoenfeld, 2013). As highlighted by Schoenfeld (2010), the effects of metabolic stress are likely to arise through metabolite build up as a result of what is called anaerobic glycolysis. Anaerobic glycolysis is simply the production of energy using glucose in the absence of oxygen. It is likely that the products of anaerobic glycolysis (e.g. lactate, hydrogen ions, creatine) initiates a series of processes (fibre recruitment, enhanced hormone release, cellular swelling, production of ROS, altered myokine production), which contribute to the hypertrophy process (Schoenfeld, 2013).. Interestingly, bodybuilding-type resistance training programs are likely to induce significant amounts of ...
Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation. Plays a general role in caspase independent cell death of tumor cells. The ratio betwween the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival ...
View Notes - Sec_2 from MBIO 2370 at Manitoba. 2-1 Lipid Catabolism for ATP Generation Triglycerides (Phospho) Lipases Phospholipids Glycerol Glycolysis TCA cycle ETC ATP Fatty acids - oxidation
We observed a generalized anoxic induction of transcripts encoding enzymes of glycolysis. Several glycolytic genes were induced by anoxia (Fig. 4A). Genes involved in alcoholic fermentation such as ADH (At1g77120), PDC1 (At4g33070), and PDC2 (At5g54960) showed a dramatic increase in expression, in agreement with Klok et al. (2002). A strong induction of two aminotransferases was also observed (see Supplemental Table II, a and b). The fermentative production of ethanol by the concerted action of pyruvate decarboxylases and alcohol dehydrogenase may be unable to consume the pyruvate accumulating as a consequence of the inactivity of the Krebs cycle. The induction of an Ala aminotransferase (At1g17290) gene and accumulation of the encoded enzyme may allow the conversion of the excess pyruvate to Ala (see Supplemental Table II, a and b). The production of Ala is indeed relevant in rice roots, reaching up to 1.2% of the dry weight after 24 h under anoxia (Reggiani and Bertani, 2003). The cytosolic ...
There is resurgent interest in cancer cell metabolism as researchers seek to understand how metabolic pathways are altered in cancer and how these alterations can be exploited for therapeutic gain. This eBriefing discusses advances in the field.
The Csr system was recently demonstrated to be a major controller of upper glycolysis fluxes (16), but its involvement in metabolic adaptation is less clear in the literature. CsrA is known to positively regulate glycolytic genes and negatively regulate gluconeogenic genes (15, 16). A study of the BarA/UvrY two-component system during the metabolic switch suggested that the Csr system is crucial for efficient adaptation between different metabolic pathways (2). Here, we showed that gene expression in the CCM (glycolysis, gluconeogenesis, the pentose phosphate pathway, and the tricarboxylic acid cycle) did not present strong discrepancies between the Csr system mutants during the acetate consumption phase, in deep contrast to the situation during glucose consumption. It will be awkward to totally rule out any control of these genes by CsrA, since regulation could be at the posttranscriptional level. The control by CsrA could also be counterbalanced by its higher sequestration by CsrB, since the ...
Platelets show decreased glycolytic rate in asthma.(A) Extracellular acidification rate (ECAR) trace in asthmatic (filled squares) and healthy controls (open sq
The first step in both anaerobic and aerobic respiration is called glycolysis. This is the process of taking one glucose (sugar) molecule and breaking it down into pyruvate and energy (2 ATP). We will discuss this in depth during aerobic respiration.. The second step in anaerobic respiration is called fermentation. Fermentation starts with pyruvate (the end product of glycolysis). Depending on the organism, pyruvate can either be fermented into ethanol (a fancy name for alcohol) or lactate (lactic acid). Fermentation releases CO2, but does not make any ATP - all ATP during anaerobic respiration is produced during glycolysis. Since glycolysis produces 2 ATP, anaerobic respiration yields 2 ATP for every molecule of glucose. Both glycolysis and fermentation take place within the cytosol/cytoplasm of a cell. In fact, the entire process of anaerobic respiration takes place in the cytosol.. Fermentation is the process by which we make wine and other types alcohol. Through an anaerobic process, yeast ...
Metabolic reprogramming is a hallmark of cancer. Compared to normal cells, cancer cells undergo metabolic reprogramming to support their proliferation, metastasis and survival. Several oncogenic signaling pathways play an important role in cancer metabolism. Alteration of enzymes like HK2, PKM2, GLS1, IDH and SHMT2 is involved in cancer metabolic reprogramming. Recently, growing evidence indicates that long non-coding RNAs (lncRNAs) play an important role in regulating cancers in many aspects including tumor cell metabolism. LncRNAs are mRNA-like transcripts that are longer than 200 nucleotides, yet do not appear to encode a protein. Many lncRNAs are differentially expressed between a variety of cancer tissues and corresponding para-cancer tissues, and their dysregulation has been connected to carcinogenesis and tumor progression. LncRNAs exert their function through miRNAs or directly through targeting metabolic reprogramming related kinases. Exploring the roles and mechanisms of lncRNAs in the
Highlights Glycolysis II. 1. Conversion of F6P to fructose-1,6-bisphosphate (F1,6BP - need to know) is catalyzed by the enzyme phoshofructokinase (PFK) (need to know). This reaction also requires ATP and is an irreversible reaction. ATP is an allosteric effector. High levels of ATP inhibit the enzyme. Low levels stimulate the enzyme. This is consistent with the energy needs of the cell - when ATP is low, cells need glycolysis to run, so PFK is turned ON. When ATP is high, cells dont need glycolysis to run, so PFK is turned OFF. PFK is a major control point for glycolysis because it stops the pathway for entry of either glucose or fructose.. 2. In the next step of glycolysis, the six carbon F1,6BP is split into two three carbon piece (DHAP and G3P) s in a reaction catalyzed by aldolase. This reaction is very unfavorable when there are equal concentrations of products and reactants. To make the reaction go forward in the cell, cells push (increase amounts of reactants) and pull (decrease ...
Hearts isolated from 11- and 12-day rat embryos were incubated in a simple salt solution to which was added the metabolic inhibitors iodoacetate, malonate, 2, 4-dinitrophenol or trypan blue. Comparisons were made between the two age-groups and it was observed that both 11- and 12-day hearts exhibited depressed contractile activity with the glycolytic inhibitor iodoacetate. Malonate did not depress contraction rate in the younger hearts but significantly depressed the rate in the older hearts. A greater inhibitory action on the older hearts as compared with the younger hearts was also produced by 2, 4-dinitrophenol. These results were interpreted as further evidence of a shift in dependence on pathways other than glycolysis between days 11 and 12 of development.. The teratogenic agent trypan blue was shown to depress contraction rate when added to the incubation medium. This effect could be reversed by adding glycolytic intermediates such as fructose-1, 6-diphosphate or alpha glycerophosphate. ...
Cancer cells increase glucose metabolism to support aerobic glycolysis. However, only some cancer cells are acutely sensitive to glucose withdrawal, and the underlying mechanism of this selective sensitivity is unclear. We showed that glucose deprivation initiates a cell death pathway in cancer cells that is dependent on the kinase RIPK1. Glucose withdrawal triggered rapid plasma membrane depolarization and an influx of extracellular calcium into the cell through the L-type calcium channel Cav1.3 (CACNA1D), followed by activation of the kinase CAMK1. CAMK1 and the demethylase PPME1 were required for the subsequent demethylation and inactivation of the catalytic subunit of the phosphatase PP2A (PP2Ac) and the phosphorylation of RIPK1. Plasma membrane depolarization, PP2Ac demethylation, and cell death were prevented by glucose and, unexpectedly, by its nonmetabolizable analog 2-deoxy-d-glucose (2-DG), a glycolytic inhibitor. These findings reveal a previously unknown function of glucose as a ...
Glucose in the bloodstream diffuses into the cytoplasm and is locked there by phosphorylation. A glucose molecule is then rearranged slightly to fructose and phosphorylated again to fructose diphosphate. These steps actually require energy, in the form of two ATPs per glucose. The fructose is then cleaved to yield two glyceraldehyde phosphates (GPs). In the next steps, energy is finally released, in the form of two ATPs and two NADHs, as the GPs are oxidized to phosphoglycerates. One of the key enzymes in this process is glyceraldehyde phosphate dehydrogenase (GPDH), which transfers a hydrogen atom from the GP to NAD to yield the energetic NADH. Due to its key position in the glycolytic pathway, biochemical assays of GPDH are often used to estimate the glycolytic capacity of a muscle cell. Finally, two more ATPs are produced as the phosphoglycerates are oxidized to pyruvate.varicofix pret. ...
In this study, tumor sub-volumes were defined based on a DPBC strategy of FDG and 64Cu-ATSM PET, and the overlap between these sub-volumes was analyzed.. Two cut-off values for FDG uptake were explored, and 64Cu-ATSM uptake was analyzed by sub-volumes based on two different time-points for image acquisition. We observed an overlap between all 64Cu-ATSM and FDG sub-volumes. However, the degree of overlap varied between cases.. Our results showed that a fairly large part of the hypoxic sub-volume as defined by 64Cu-ATSM was not included in a boost volume based on FDG uptake with the chosen thresholds. However, the hypoxic sub-volume did not encompass the FDG uptake either, and it therefore seems attractive to include both tracers in RT planning considering their association to treatment outcome and prognosis.. The Cu24 sub-volume was predominantly included in the BTV consisting of FDG (FDG40 or FDG50) and Cu3. This result suggests that the temporal variations of 64Cu-ATSM uptake might be taken ...
A 71 years old patient diagnosed with metastatic lung carcinoid tumor (hepatic, splenic and osseous metastasis) presents a subcarinal lymphadenopathy with different uptake patterns depending on the tracer used during the study. We have performed a comparative 18F-FDG and 68Ga-DOTATOC PET/CT study where we have noticed an increased FDG uptake in the posterior right corner of the lesion while the uptake of DOTATOC was mostly in the anterior left corner of the lesion. This probably means that the posterior right corner contains cells with high glycolytic metabolism but, at the same time, decreased SSTR expression while the anterior left corner presents low glycolytic metabolism with high levels of SSTR expression. To sum up, this adenopathy is presenting 2 different types of neuroendocrine cell populations: well differentiated in the anterior left corner and poorly differentiated in the posterior right corner.. ...
Macrophages activated by the TLR4 agonist LPS undergo dramatic changes in their metabolic activity. We here show that LPS induces expression of the key metabolic regulator Pyruvate Kinase M2 (PKM2). Activation of PKM2 using two well-characterized small molecules, DASA-58 and TEPP-46, inhibited LPS-induced Hif-1α and IL-1β, as well as the expression of a range of other Hif-1α-dependent genes. Activation of PKM2 attenuated an LPS-induced proinflammatory M1 macrophage phenotype while promoting traits typical of an M2 macrophage. We show that LPS-induced PKM2 enters into a complex with Hif-1α, which can directly bind to the IL-1β promoter, an event that is inhibited by activation of PKM2. Both compounds inhibited LPS-induced glycolytic reprogramming and succinate production. Finally, activation of PKM2 by TEPP-46 in vivo inhibited LPS and Salmonella typhimurium-induced IL-1β production, while boosting production of IL-10. PKM2 is therefore a critical determinant of macrophage activation by ...
Naked mole-rats live in large colonies deep underground in hypoxic conditions. Park et al. found that these animals fuel anaerobic glycolysis with fructose by a rewired pathway that avoids tissue damage (see the Perspective by Storz and McClelland). These results provide insight into the adaptations that this strange social rodent has to make for life underground. They also have implications for medical practice, particularly for understanding how to protect tissues from hypoxia.. Science, this issue p. 307; see also p. 248 ...
The effect can be explained; as the yeast being facultative anaerobes can produce energy using two different metabolic pathways. While the oxygen concentration is low, the product of glycolysis, pyruvate, is turned into ethanol and carbon dioxide, and the energy production efficiency is low (2 moles of ATP per mole of glucose). If the oxygen concentration grows, pyruvate is converted to acetyl CoA that can be used in the citric acid cycle, which increases the efficiency to 32 moles of ATP per mole of glucose. Therefore, about 16 times as much glucose must be consumed anaerobically as aerobically to yield the same amount of ATP.[2]. Under anaerobic conditions, the rate of glucose metabolism is faster, but the amount of ATP produced (as already mentioned) is smaller. When exposed to aerobic conditions, the ATP and Citrate production increases and the rate of glycolysis slows, because the ATP and citrate produced act as allosteric inhibitors for phosphofructokinase 1, the third enzyme in the ...
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Seyfried & DAgostino 2014 Experiment showing that mDNA is the essential transformation leading to cancer. The tumorigenic phenotype is suppressed when normal mitochondria are transferred to the tumor cell cytoplasm. On the other hand, the tumorigenic phenotype is enhanced when tumor mitochondria are transferred to a normal cell cytoplasm. These findings further suggest that tumorigenesis is dependent more on mitochondrial function than on the types of mutations in the nucleus.. Unique process of lactic acid fermentation in presence of oxygen It is important to recognize that pyruvate is produced through aerobic glycolysis in most normal cells of the body that use glucose for energy. The reduction of pyruvate to lactate distinguishes the tumor cells from most normal cells, which fully oxidize pyruvate to CO2 and water for adenosine triphosphate (ATP) production through the tricarboxylic acid (TCA) cycle and the electron transport chain chain (56). Aerobic glycolysis with lactate production can ...
Effective strategies to treat or prevent staphylococcal infection have been limited by the ability of these organisms to adapt to a variety of clinical settings. Such adaptation includes changes in metabolic activity and in the expression of virulence factors and toxins. Depending on the site of infection, Staphylococcus aureus proliferates using aerobic metabolism or anaerobic pathways at oxygen‐depleted sites [2]. It adapts to aerobic glycolysis at many sites including skin and immune cells [3]. The importance of neutrophil function in the effective eradication of S. aureus at all sites of infection and under these different metabolic conditions has been well documented. These organisms, nonetheless, are highly resistant to phagocytic clearance and express multiple gene products that directly thwart immune function [4].. In contrast to many human pathogens that evade proinflammatory signaling to survive, S. aureus is unusually resistant to phagocytic clearance and persists despite the ...
Tumors also metabolize differently from normal cells. They convert sugar into energy incredibly fast and produce lactic acid, a chemical normally resulting from metabolism that takes place in the absence of oxygen. In other words, cancer cells ferment, and scientists dont know why. This phenomenon is known as the Warburg effect, named for Otto Warburg, a German biochemist who won a Nobel Prize in 1931 for his discoveries about oxygen and metabolism. Up to 80 percent of cancers display the Warburg effect. Researchers know that many cancers depend on the Warburg effect for their survival, but they dont know why. To Davies, the strange way in which tumors metabolize also speaks of cancers ancient past: They are behaving as if there were no oxygen available.. Malignant cells also produce acid, which Mark Vincent, another proponent of the atavistic theory, says creates an environment reminiscent of the atmosphere during the proterozoic eon, when life first appeared on Earth. The similarity between ...
Erythrocytes in mammals are anucleate when mature, meaning that they lack a cell nucleus and as a result, have no DNA. Red blood cells have nuclei during early phases of development, but extrude them as they mature in order to provide more space for hemoglobin. In comparison, the erythrocytes of nearly all other vertebrates have nuclei; the only known exception being salamanders of the Batrachoseps genus.[4] Mammalian erythrocytes also lose their other organelles such as their mitochondria. As a result, red blood cells produce ATP through glycolysis only and therefore use none of the oxygen they carry. Furthermore, red cells do not have an insulin receptor and thus glucose uptake is not regulated by insulin. Because of the lack of nucleus and organelles, the red blood cells cannot synthesize any RNA so they cannot divide or repair themselves. Mammalian erythrocytes are biconcave disks: flattened and depressed in the center, with a dumbbell-shaped cross section. This shape (as well as the loss of ...
Generally, stem cells show low oxidative phosphorylation and high glycolytic activity to synthesize ATP. Thus, stem cells favor enzymatic pathways synthesizing ATP anaerobically. This observation suggests that stem cells in a hypoxic condition are metabolically different from progenitor cells.. Niches or niche cells for quiescent stem cells are located in hypoxic regions of tissues not rich in vasculature, such as the trabecular zone for HSCs and bulges for pigmented stem cells (Jang and Sharkis, 2007). Lower organisms such as C. elegans (Golden and Riddle, 1984; Lee et al., 2003) and bacteria (Cho and Eagon, 1967) enter a resting phase characterized by suppressed metabolism and decreased cell cycling in response to the environmental influences of low-temperature or low-nutrients. This adaptation is crucial for their survival. Recently, an evolutionarily conserved mechanism regulating the resting phase of mammalian HSCs is being established through the analysis of mice deficient in FOXO ...
To the Editor:. Jóhannsson et al1 have recently observed upregulation of the Monocarboxylate transporter 1 (MCT1) in congestive heart failure (CHF). The implied increased uptake of exogenous (systemic) lactate confirms the potential significance of increased carbohydrate metabolism as a compensatory adaptation in CHF and also identifies a potential therapeutic focus. However, 3 points deserve emphasis:. (1) Although increased MCT-1 appears to be a feature of at least a subgroup of ventricular dysfunction, certainly indicating an increased reliance on systemic lactate, Jóhannsson et al interpret a lack of comparable glucose transporter (Glut-1 and -4) upregulation to suggest endogenous glycolytically derived lactate is relatively insignificant. Their assertion derives from the widely held traditional notion that fatty acid metabolism (FAM), coincidentally the major energy source in normal hearts, antagonizes glycolysis and vice versa.. Contemporary studies, while accepting a relative fuel ...
Clinically approved therapies that target angiogenesis in tumors and ocular diseases focus on controlling pro-angiogenic growth factors in order to reduce aberrant microvascular growth. Although research on angiogenesis has revealed key mechanisms that regulate tissue vascularization, therapeutic success has been limited owing to insufficient efficacy, refractoriness and tumor resistance. Emerging concepts suggest that, in addition to growth factors, vascular metabolism also regulates angiogenesis and is a viable target for manipulating the microvasculature. Recent studies show that endothelial cells rely on glycolysis for ATP production, and that the key glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) regulates angiogenesis by controlling the balance of tip versus stalk cells. As endothelial cells acquire a tip cell phenotype, they increase glycolytic production of ATP for sprouting. Furthermore, pharmacological blockade of PFKFB3 causes a transient, partial ...
Terms You should have a working knowledge of the following terms: alcohol fermentation cellular respiration cytosol dehydrogenase electronegativity fermentation glycolysis lactic acid fermentation NAD+ NADH oxidation pyruvate redox reduction substrate-lev
2016). As such, the research performed over the past decade using simple systems and metabolomics has generated a general conceptual framework that appears generally applicable to many systems. The findings suggest that glucose is primarily converted to lactate in proliferative metabolism. The fate of glucose in proliferating cells trifurcates toward the pentose phosphate pathway, glucosamine biosynthesis, and glycolytic degradation to lactate. The pentose phosphate pathway generates an essential component of nucleic acids: ribose, which would then be reduced to deoxyribose by deoxyribonucleotic reductase. Glucosamine, which is at the crossroads of glucose and glutamine metabolism, is critical for carbohydrate synthesis and posttranslational modification via O-linked glycosylation, for example. The conversion of glucose to lactate with the regeneration of NAD+ from NADH ensures the upstream glycolytic flux through GAPDH, which depends on NAD+, continues to funnel pyruvate downstream for its ...
as inhibitor of tumour cell energy metabolism. The Warburg effect is the elevated glucose metabolism to lactic acid (glycolysis), even in the presence of oxygen. While it has been recognized as the most common biochemical phenotype of cancer for over 80 years, its biochemical and genetic basis remained unknown for over 50 years. Work focused on elucidating the underlying mechanism(s) of the Warburg effect commenced in the authors laboratory in 1969. By 1985 two important findings emerged related directly to the basis of the Warburg effect, the first that the mitochondrial content of tumors exhibiting this phenotype is markedly decreased relative to the tissue of origin, and the second that such mitochondria have markedly elevated amounts of the enzyme hexokinase-2 (HK2) bound to their outer membrane.. HK2 is the first of a number of enzymes in cancer cells involved in metabolizing the sugar glucose to lactic acid. At its mitochondrial location HK2 binds at/near the protein VDAC (voltage ...
Rod-derived cone viability factor (RdCVF) is an inactive thioredoxin secreted by rod photoreceptors that protects cones from degeneration. Because the