Metabolism consisting of catabolic and anabolic processes encompasses the sum of all chemical conversions in a cell or organism. (a) Anabolism and (b) catabolism.

Metabolism consisting of catabolic and anabolic processes encompasses the sum of all chemical conversions in a cell or organism. (a) Anabolism and (b) catabolism.

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Mature human erythrocytes are dependent on anerobic glycolysis, i.e. catabolism (oxidation) of one glucose molecule to produce two ATP and two lactate molecules. Proliferating tumor cells mimick mature human erythrocytes to glycolytically generate two ATP molecules. They deliberately avoid or switch off their respiration, i.e. tricarboxylic acid (T...

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... lipids, and proteins) ultimately resulting in a gain of chemical energy (ATP) and reductive equivalents. These processes ensure the functioning of cells and organism and thus life itself ( Figure 6). ...

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Background: Ribulose 5-phosphate (Ru5P) and guanosine 5'-triphosphate (GTP) are two key precursors of riboflavin, whereby Ru5P is also a precursor of GTP (purine de novo synthesis pathway). As a product of the oxidative pentose phosphate pathway (OPPP), Ru5P can flow back into the Embden-Meyerhof-Parnas pathway (EMP) through the non-oxidative pento...

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... Despite low glucose concentration in the TME, SGLT2 can enhance glucose uptake by cancer cells. Meanwhile, inhibiting SGLT2 suppresses the proliferation of cancer cells, SGLT2, and not GLUTs, promotes PC progression (38,39). Du et al. analyzed 88 included PC tissues and found that SGLT1 was overexpressed in pancreatic ductal adenocarcinoma (PDAC) and its expression correlated with overall survival (OS) and progression-free survival (PFS) of patients. ...
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Early and accurate diagnosis and treatment of pancreatic cancer (PC) remain challenging endeavors globally. Late diagnosis lag, high invasiveness, chemical resistance, and poor prognosis are unresolved issues of PC. The concept of metabolic reprogramming is a hallmark of cancer cells. Increasing evidence shows that PC cells alter metabolic processes such as glucose, amino acids, and lipids metabolism and require continuous nutrition for survival, proliferation, and invasion. Glucose metabolism, in particular, regulates the tumour microenvironment (TME). Furthermore, the link between glucose metabolism and TME also plays an important role in the targeted therapy, chemoresistance, radiotherapy ineffectiveness, and immunosuppression of PC. Altered metabolism with the TME has emerged as a key mechanism regulating PC progression. This review shed light on the relationship between TME, glucose metabolism, and various aspects of PC. The findings of this study provide a new direction in the development of PC therapy targeting the metabolism of cancer cells.
... The increased PGAM expression favors cancer cell proliferation and tumor growth by regulating glycolysis, anabolic biosynthesis, and other nonmetabolic functions (50)(51)(52)(53)(54)(55). Similar to the highly proliferating cancer cells, intraerythrocytic Plasmodium parasite metabolism is not only required to generate ATP but also to support the rapid rates of proliferation and replication (44,56). Glycolysis is the major energy-yielding source for P. falciparum. ...
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The glycolytic enzyme phosphoglycerate mutase (PGM) is of utmost importance for overall cellular metabolism and has emerged as a novel therapeutic target in cancer cells. This enzyme is also conserved in the rapidly proliferating malarial parasite Plasmodium falciparum, which have a similar metabolic framework as cancer cells and rely on glycolysis as the sole energy-yielding process during intraerythrocytic development. There is no redundancy among the annotated phosphoglycerate mutase enzymes in Plasmodium and PfPGM1 is absolutely required for the parasite survival as evidenced by conditional knockdown in our study. A detailed comparison of PfPGM1 with its counterparts followed by in-depth structure-function analysis revealed unique attributes of this parasitic protein. Here, we report for the first time the importance of oligomerization for the optimal functioning of the enzyme in vivo, as earlier studies in eukaryotes only focused on the effects in vitro. We show single point mutation of the amino acid residue W68 led to complete loss of tetramerization and diminished catalytic activity in vitro. Additionally, ectopic expression of the wild type PfPGM1 protein enhanced parasite growth, whereas the monomeric form of PfPGM1 failed to provide growth advantage. Furthermore, mutation of the evolutionarily conserved residue K100 led to a drastic reduction in enzymatic activity. The indispensable nature of this parasite enzyme highlights the potential of PfPGM1 as a therapeutic target against malaria, and targeting the interfacial residues critical for oligomerization can serve as a focal point for promising drug development strategies that may not be restricted to malaria only.
... For many years, the dual role of NO in cancer has been recognized, and more and more studies are investigating deeper mechanisms. The inhibition of oxidative phosphorylation in tumor cells was found to lead to elevated glycolytic metabolism (Ghashghaeinia et al., 2019;Najjar et al., 2019). Compared with their differentiated offspring, stem cells rely more on glycolysis which preferentially metabolizes lactate via mitochondrial respiration (Deshmukh et al., 2016;Liang et al., 2020), indicating that the changes occurring in metabolism occur earlier than those in stemness (Shyh- Chang et al., 2013). ...
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Paris saponin has shown great therapeutic value in cancer therapy. We used isolated Paris saponin II (PSII), an active component of Paris saponin, and demonstrated its antitumor effect on human head and neck squamous cell carcinoma cell lines. Additionally, we investigated its mechanisms of action in vivo by establishing a xenograft mouse model. The results showed that PSII had presented strong anticancer effects on both hypopharyngeal malignant tumor cell lines (FaDu) and laryngeal carcinoma cell lines (Tu212 and Tu686). In addition, we successfully isolated and cultured the head and neck squamous stem cells and the primary fibroblasts to perform metabonomics studies. The results showed that RPII remarkably decreased energy metabolism, and type III nitric oxide synthase 3 (NOS3) may be a target to block tumor growth. Furthermore, we found that PSII inhibited HNSCC proliferation and metastasis by inhibiting the nitric oxide metabolic pathway. Overall, these results demonstrated that PSII is a potent anticancer agent, and the metabonomics analysis is a valuable tool to investigate and establish the antitumor effects of traditional Chinese medicines.
... Obesity-and psoriasis-associated chronic lowgrade inflammation and NFĸB activation are two sides of the same coin that perpetuate each other. It is known that NFĸB is a positive physiological regulator of glycolysis [106], for review see [107]. The following review clearly illustrates the relationship between the anti-inflammatory effects of insulin and the pro-inflammatory effects of glucose with NFĸB as a common target [108]. ...
... For adequate supply of the organism with molecular oxygen, hRBCs divert 20% of the uptaken glucose to Rapoport and Luebering glycolytic shunt [115], for review see [107]. In this process erythrocyte 2,3-bisphosphoglycerate (2,3-BPG) plays a central role. ...
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Enucleated mature human erythrocytes possess NFĸBs and their upstream kinases. There is a negative correlation between eryptosis (cell death of erythrocytes) and the amount of NFĸB subunits p50 and Rel A (p65). This finding is based on the fact that young erythrocytes have the highest levels of NFĸBs and the lowest eryptosis rate, while in old erythrocytes the opposite ratio prevails. Human erythrocytes (hRBCs) effectively control the homeostasis of the cell membrane permeable anti-inflammatory signal molecule hydrogen sulfide (H2S). They endogenously produce H2S via both non-enzymic (glutathione-dependent) and enzymic processes (mercaptopyruvate sulfur transferase-dependent). They uptake H2S from diverse tissues and very effectively degrade H2S via methemoglobin (Hb-Fe³⁺)-catalyzed oxidation. Interestingly, a reciprocal correlation exists between the intensity of inflammatory diseases and endogenous levels of H2S. H2S deficiency has been observed in patients with diabetes, psoriasis, obesity, and chronic kidney disease (CKD). Furthermore, endogenous H2S deficiency results in impaired renal erythropoietin (EPO) production and EPO-dependent erythropoiesis. In general we can say: dynamic reciprocal interaction between tumor suppressor and oncoproteins, orchestrated and sequential activation of pro-inflammatory NFĸB heterodimers (RelA-p50) and the anti-inflammatory NFĸB-p50 homodimers for optimal inflammation response, appropriate generation, subsequent degradation of H2S etc., are prerequisites for a functioning cell and organism. Diseases arise when the fragile balance between different signaling pathways that keep each other in check is permanently disturbed. This work deals with the intact anti-inflammatory hRBCs and their role as guarantors to maintain the redox status in the physiological range, a basis for general health and well-being.
... In the first phase, the cell invests two ATP molecules to convert one glucose molecule into two glyceraldehyde-3-phosphate (G3P) molecules. In the payoff phase, G3P molecules are metabolized to two molecules of pyruvate, four ATP, and two NADH, resulting in a net glycolytic gain of two ATP(Ghashghaeinia et al., 2019;van Wijk & van Solinge, 2005). In cells that primarily rely on aerobic respiration, pyruvate is further metabolized in the oxygen-dependent Krebs cycle and oxidative phosphorylation, producing 36 ATP molecules overall from one glucose molecule(Ghashghaeinia et al., 2019). ...
... In the payoff phase, G3P molecules are metabolized to two molecules of pyruvate, four ATP, and two NADH, resulting in a net glycolytic gain of two ATP(Ghashghaeinia et al., 2019;van Wijk & van Solinge, 2005). In cells that primarily rely on aerobic respiration, pyruvate is further metabolized in the oxygen-dependent Krebs cycle and oxidative phosphorylation, producing 36 ATP molecules overall from one glucose molecule(Ghashghaeinia et al., 2019). ...
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Hydrogen sulfide (H2S) is a gasotransmitter that regulates both physiological and pathophysiological processes in mammalian cells. Recent studies have demonstrated that H2S promotes aerobic energy production in the mitochondria in response to hypoxia, but its effect on anaerobic energy production has yet to be established. Glycolysis is the anaerobic process by which ATP is produced through the metabolism of glucose. Mammalian red blood cells (RBCs) extrude mitochondria and nucleus during erythropoiesis. These cells would serve as a unique model to observe the effect of H2S on glycolysis-mediated energy production. The purpose of this study was to determine the effect of H2S on glycolysis-mediated energy production in mitochondria-free mouse RBCs. Western blot analysis showed that the only H2S-generating enzyme expressed in mouse RBCs is 3-mercaptopyruvate sulfurtransferase (MST). Supplement of the substrate for MST stimulated, but the inhibition of the same suppressed, the endogenous production of H2S. Both exogenously administered H2S salt and MST-derived endogenous H2S stimulated glycolysis-mediated ATP production. The effect of NaHS on ATP levels was not affected by oxygenation status. On the contrary, hypoxia increased intracellular H2S levels and MST activity in mouse RBCs. The mitochondria-targeted H2S donor, AP39, did not affect ATP levels of mouse RBCs. NaHS at low concentrations (3–100 μM) increased ATP levels and decreased cell viability after 3 days of incubation in vitro. Higher NaHS concentrations (300–1000 μM) lowered ATP levels, but prolonged cell viability. H2S may offer a cytoprotective effect in mammalian RBCs to maintain oxygen-independent energy production.
... Гликолитические ферменты образуют функциональный метаболический комплекс, называемый метаболоном, в котором 3 фермента (фосфофруктокиназа, альдолаза и глицеральдегид-3-фосфатдегидрогеназа) непосредственно соединяются с N-доменом белка полосы 3, тогда как остальные энзимы не имеют с ним прямых контактов. Ферменты метаболона активируются при их фосфорили-ровании или оксигемоглобином [26,35,42,49]. ...
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The article reviews literature on the organization of the erythrocyte plasmalemma and its rearrangements at different periods of the cell lifespan. In the absence of a nucleus and organelles, the plasmalemma is the only structural element of erythrocytes involved in all processes of their vital activity. The plasmalemma supports the disk-like shape of the erythrocyte, provides its ability to reversible deformation, maintains intracellular homeostasis, participates in gas transport and energy metabolism, also transfers hormones, enzymes, antibodies, medicines and other substances on its surface. The polyfunctionality of the plasmalemma is provided by the peculiarities of its lipid, protein, and carbohydrate composition, as well as by the presence of a unique cytoskeleto n, morphologically associated with the erythrocyte membrane. The plasmalemma has the substantial modifications during the erythrocyte lifespan, namely, in maturation of reticulocytes, in the processes of functioning, aging, and cell death. Biochemical rearrangements of the plasmalemma serve as triggers for events such as membrane vesiculation, eryptosis, and elimination of senescent erythrocytes by macrophages. Age-related changes in the erythrocyte plasmalemma are adoptive in nature and aimed at maintaining cellular homeostasis and functional activity of these formed elements during a four-month stay in the bloodstream.
... Most normal cells mainly rely on the oxidative metabolism to produce energy, but tumor cells still choose to glycolysis pathway even in the sufficient oxygen [14]. The glycolysis pathway could produce energy quickly, which could satisfy the cell rapid proliferation [15]. Lactate produced from glycolysis promotes angiogenesis, cell invasion and immunosuppression, which promotes tumorigenesis [16]. ...
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Background Endometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue outside the uterus. Endometriosis often causes infertility, which brings physical and mental pain to patients and their families. Methods We examined the functions of heat shock factor 1 (HSF1) in endometriosis development through cell count assay, cell-scratch assay and clone formation experiments. We used quantitative real-time PCR (qRT-PCR) and Western blot (WB) to detect HSF1 expression. Glucose and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we used a HSF1 inhibitor-KRIBB11 to establish a mouse model of endometriosis. Results Our data demonstrated that HSF1 promoted endometriosis development. Interestingly, HSF1 enhanced glycolysis via up-regulating PFKFB3 expression in endometriosis cells, which was a key glycolysis enzyme. Consistently, the HSF1 inhibitor KRIBB11 could abrogate endometriosis progression in vivo and in vitro. Conclusions Findings indicate that HSF1 plays an important role in endometriosis development, which might become a new target for the treatment of endometriosis. Electronic supplementary material Supplementary data are available.
... However, it is necessary to understand the mechanisms of each gene of metabolism during cancer progression. Glycolysis plays an initial role in the metabolic network, which controls the carbohydrate products and synthesis of downstream side-chain products (including the pentose phosphate pathway, amino acid and fatty acid biosynthesis) 2 . Glycolytic enzymes are an aspect that needs more attention in cancer research. ...
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Phosphoglycerate kinase (PGK) is involved in glycolytic and various metabolic events. Dysfunction of PGK may induce metabolic reprogramming and the Warburg effect. In this study, we demonstrated that PGK1, but not PGK2, may play a key role in tumorigenesis and is associated with metastasis. We observed an inverse correlation between PGK1 and the survival rate in several clinical cohorts through bioinformatics statistical and immunohistochemical staining analyses. Surprisingly, we found that PGK1 was significantly increased in adenocarcinoma compared with other subtypes. Thus, we established a PGK1-based proteomics dataset by a pull-down assay. We further investigated HIV-1 Tat Specific Factor 1 (HTATSF1), a potential binding partner, through protein–protein interactions. Then, we confirmed that PGK1 indeed bound to HTATSF1 by two-way immunoprecipitation experiments. In addition, we generated several mutant clones of PGK1 through site-directed mutagenesis, including mutagenesis of the N-terminal region, the enzyme catalytic domain, and the C-terminal region. We observed that even though the phosphoglycerate kinase activity had been inhibited, the migration ability induced by PGK1 was maintained. Moreover, our immunofluorescence staining also indicated the translocation of PGK1 from the cytoplasm to the nucleus and its colocalization with HTATSF1. From the results presented in this study, we propose a novel model in which the PGK1 binds to HTATSF1 and exerts functional control of cancer metastasis. In addition, we also showed a nonenzymatic function of PGK1.
... Of note, RBC dependency on glycolysis as the sole source of energy production in the form of Adenosine Triphosphate (ATP) has helped to understand parallelisms between the Warburg phenotype of cancer cells and RBC metabolism. 27 Observation of FADS activity in cancer cells suggests that delta-5 desaturase (D5D) and delta-6 desaturase (D6D), which are encoded by FADS1 and FADS2, respectively, are required for the synthesis of highly unsaturated fatty acids (HUFAs). 26 Additional studies suggest a role for FADS2 and FADS5 (delta-9 desaturase-D9D or stearoyl-CoA desaturase) in mediating cancer cell plasticity in hepatocellular carcinoma 28 and leukemia. ...
Article
Background: Increases in the red blood cell (RBC) degree of fatty acid desaturation are reported in response to exercise, aging, or diseases associated with systemic oxidant stress. However, no studies have focused on the presence and activity of fatty acid desaturases (FADS) in the mature RBC. Study design and methods: Steady state metabolomics and isotope-labeled tracing experiments, immunofluorescence approaches, and pharmacological interventions were used to determine the degree of fatty acid unsaturation, FADS activity as a function of storage, oxidant stress, and G6PD deficiency in human and mouse RBCs. Results: In 250 blood units from the REDS III RBC Omics recalled donor population, we report a storage-dependent accumulation of free mono-, poly-(PUFAs), and highly unsaturated fatty acids (HUFAs), which occur at a faster rate than saturated fatty acid accumulation. Through a combination of immunofluorescence, pharmacological inhibition, tracing experiments with stable isotope-labeled fatty acids, and oxidant challenge with hydrogen peroxide, we demonstrate the presence and redox-sensitive activity of FADS2, FADS1, and FADS5 in the mature RBC. Increases in PUFAs and HUFAs in human and mouse RBCs correlate negatively with storage hemolysis and positively with posttransfusion recovery. Inhibition of these enzymes decreases accumulation of free PUFAs and HUFAs in stored RBCs, concomitant to increases in pyruvate/lactate ratios. Alterations of this ratio in G6PD deficient patients or units supplemented with pyruvate-rich rejuvenation solutions corresponded to decreased PUFA and HUFA accumulation. Conclusion: Fatty acid desaturases are present and active in mature RBCs. Their activity is sensitive to oxidant stress, storage duration, and alterations of the pyruvate/lactate ratio.
... In a third step, fructose-6-phosphate is phosphorylated by phosphofructokinase (PFK)-1 and PFK-2 into the unstable fructose-1,6-biphosphate and the relatively stable fructose-2,6-biphosphate (19), respectively. Glucose 6-phosphate is also converted into glyceraldehyde-3-phosphate (25), which is subsequently converted into glycerate-1,3-biphosphate, and glycerate-1,3-biphosphate is converted into 3-phosphoglycerate by phosphoglycerate kinase (19). Subsequently, phosphoglyceromutase drives the isomerization of 3-phosphoglycerate to phosphoglycerate 2-phosphate, followed by the formation of phosphoenolpyruvate Figure 1. ...
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Mammalian target of rapamycin (mTOR) serves an important role in regulating various biological processes, including cell proliferation, metabolism, apoptosis and autophagy. Among these processes, energy metabolism is the dominant process. The metabolism of not only amino acids, fattyacidsandlipids,butalsothatofnucleotidesandglucosehas been indicated to be regulated by mTOR. Aerobic glycolysis, which is a specific form of glucose metabolism, is prevalent in carcinomas, and it has been considered to be a potential target for cancer therapy. In reviewing the complexity of the mTOR pathway, it is important to elucidate the central role and detailed pathway via which mTOR regulates glycolysis. In the present study, the complex mechanisms via which mTOR regulates aerobic glycolysis were comprehensively reviewed to highlight the potential of drug development via targeting the molecules associated with mTOR and glycolysis and to further provide strategies for the clinical treatment of cancer. Contents 1. Introduction 2. mTOR is central to metabolism in cancer 3. Glycolysis is a complex process 4. mTOR signaling pathway regulates glycolysis 5. Perspectives.