•Since there is no exact cure discovered for cancer, studies have focused on different hallmarks of cancer.•Warburg’s hypothesis has been a step for the studies in this subject.•With the knowledge of ...crucial players in glycolysis takes place in cancer cells, therapies will be more accurate.
Cancer is the second most important cause of death and new therapy modalities continue to be developed and evolved. Cancer cells’ metabolism is far different from the normal, healthy cells; they are more metabolically active, have higher proliferation rate and could able to resist to cell death pathways like apoptosis. It is known that in addition to increasing the expression of enzymes that are crucial in glycolysis for much more energy production, cancer cells produce energy from lactic acid fermentation after glycolysis. In 1920s, Warburg has claimed that cancer cells are more active in glycolysis than normal cells and use much more glucose in order to obtain more ATP for metabolic activities, then this is named as Warburg effect. After that; new methodologies and therapeutics that target metabolism, began to be attractive subject in cancer studies. Therefore, the main genes, enzymes and factors are begun to investigate and further studied for understanding their roles in metabolism of cancer cells.
Disordered metabolic states, which are characterised by hypoxia and elevated levels of metabolites, particularly lactate, contribute to the immunosuppression in the tumour microenvironment (TME). ...Excessive lactate secreted by metabolism-reprogrammed cancer cells regulates immune responses via causing extracellular acidification, acting as an energy source by shuttling between different cell populations, and inhibiting the mechanistic (previously ‘mammalian’) target of rapamycin (mTOR) pathway in immune cells. This review focuses on recent advances in the regulation of immune responses by lactate, as well as therapeutic strategies targeting lactate anabolism and transport in the TME, such as those involving glycolytic enzymes and monocarboxylate transporter inhibitors. Considering the multifaceted roles of lactate in cancer metabolism, a comprehensive understanding of how lactate and lactate-targeting therapies regulate immune responses in the TME will provide insights into the complex relationships between metabolism and antitumour immunity.
Axon degeneration is a hallmark of many neurodegenerative disorders. The current assumption is that the decision of injured axons to degenerate is cell-autonomously regulated. Here we show that ...Schwann cells (SCs), the glia of the peripheral nervous system, protect injured axons by virtue of a dramatic glycolytic upregulation that arises in SCs as an inherent adaptation to axon injury. This glycolytic response, paired with enhanced axon-glia metabolic coupling, supports the survival of axons. The glycolytic shift in SCs is largely driven by the metabolic signaling hub, mammalian target of rapamycin complex 1, and the downstream transcription factors hypoxia-inducible factor 1-alpha and c-Myc, which together promote glycolytic gene expression. The manipulation of glial glycolytic activity through this pathway enabled us to accelerate or delay the degeneration of perturbed axons in acute and subacute rodent axon degeneration models. Thus, we demonstrate a non-cell-autonomous metabolic mechanism that controls the fate of injured axons.
Most tumors exhibit increased glucose metabolism to lactate, however, the extent to which glucose-derived metabolic fluxes are used for alternative processes is poorly understood. Using a ...metabolomics approach with isotope labeling, we found that in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through phosphoglycerate dehydrogenase (PHGDH). An analysis of human cancers showed that PHGDH is recurrently amplified in a genomic region of focal copy number gain most commonly found in melanoma. Decreasing PHGDH expression impaired proliferation in amplified cell lines. Increased expression was also associated with breast cancer subtypes, and ectopic expression of PHGDH in mammary epithelial cells disrupted acinar morphogenesis and induced other phenotypic alterations that may predispose cells to transformation. Our findings show that the diversion of glycolytic flux into a specific alternate pathway can be selected during tumor development and may contribute to the pathogenesis of human cancer.
Raffia palm (Raphia hookeri) wine (RPW) is amongst the natural products from plants, utilized singly or in combination with other medicinal plants for the treatment of several ailments including ...Diabetes Mellitus (DM). However, there is a scientific dearth on its antidiabetic activity.
The antidiabetic effect of RPW and its possible mechanism of actions were investigated in diabetic rats.
Four groups of male SD rats were first supplied with 10% fructose solution ad libitum for 2 weeks instead of drinking water followed by an intraperitonial injection of streptozotocin (40 mg/kg) to induce diabetes. Two diabetic groups were administered RPW at 150 and 300 mg/kg bodyweight (BW) respectively; a group was administered with metformin, while the other one was served as a negative control. Two groups of normal rats were administered with water and RPW (300 mg/kg BW) and served as normal control and normal toxicology group, respectively.
Five weeks treatment of RPW led to significant (p < 0.05) increase in serum insulin and HDL-c levels with concomitant reduction in blood glucose, fructosamine, ALT, uric acid, triglycerides and LDL-c levels in diabetic rats. Rats treated with RPW had elevated levels of GSH, SOD, catalase, ATPase and α-amylase activities, while reduced NO level and myeloperoxidase activity was observed in their serum and pancreatic tissues. RPW also improved pancreatic β-cell function and restored β- and acinar cells morphology, and capillary networks. The activities of glycogen phosphorylase, fructose 1,6 biphosphatase, glucose-6-phosphatase, and acetylcholinesterase were also inhibited in RPW-treated diabetic rats, with concomitant down regulation of Nrf2 gene expression.
The data of this study suggest that RPW modulates glucose homeostasis by enhancing insulin secretion as well as inhibiting redox imbalance in diabetic rats, which may be attributed to the synergetic effects of its phytochemical constituents as identified by GC-MS analysis.
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In this study, approximately half the patients with red-cell pyruvate kinase deficiency who were treated with mitapivat had an improvement in their hemoglobin level and decreased hemolysis that was ...sustained for nearly 3 years. Patients who had missense mutations that allowed for synthesis of a hypofunctioning enzyme were most likely to have a response.
•Lipopolysaccharide perturbs enzymes of glycolytic pathway.•Lipopolysaccharide inhibits energy metabolizing enzymes of the oxidative phosphorylation.•Methanolic extract of Buchholzia Coriacea seed ...(MEBCS) attenuates lipopolysaccharide-induced perturbations of glycolysis.•Methanolic extract of Buchholzia Coriacea seed (MEBCS) attenuates lipopolysaccharide-induced perturbations of oxidative phosphorylation enzymes in mice.
The safety of lipopolysaccharide (LPS)-containing foods has been questioned and the concerns are understandable. Buchholzia coriacea seeds have been widely applied in folkloric medicine due to their nutritional and therapeutic potential. The aim of the study is to evaluate the attenuation of methanolic extract of Buchholzia coriacea seed (MEBCS) on LPS-induced energy metabolism perturbations. Eighteen BALB/c mice were divided into three groups of 6 mice each. Group 1 (control) received distilled water and physiological saline for 7 days. Group 2 (LPS only) received 4 mg/Kg LPS intraperitoneally on the 7th day of administration, while Group 3 (LPS+MEBCS) were pre-treated with 250 mg/kg MEBCS orally for 6 days prior to administration of LPS (4 mg/kg) on the 7th day. The experimental animals were sacrificed afterward. Glycolytic and oxidative phosphorylation enzymes were assessed in the heart, kidney, spleen, lymphocytes, and erythrocytes. Glycolytic enzymes (lactate dehydrogenase, hexokinase, aldolase, and NADase) and oxidative phosphorylation enzymes such malate dehydrogenase, succinate dehydrogenase and electron transport complexes I+III, II+III, and IV) activities were significantly decreased (P> 0.05) by LPS. Pre-treatment with MEBCS attenuates the decrease in activity observed. The findings of this study indicated that MEBCS has the potential of attenuating perturbations of energy metabolism induced by lipopolysaccharides.
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•Glycolysis was delayed in meat at the chilling rate of 23.0 °C/h and 25.1 °C/h.•Chilling treatment maintained higher activity of glycolytic enzymes.•Chilling treatment promoted the phosphorylation ...of glycolytic enzymes.•Chilling treatment inhibited the acetylation of ALDOA, TPI1 and LDH.•Chilling treatment may delay rigor by phosphorylation and acetylation.
The aim of this study was to investigate the effects of chilling rate on phosphorylation and acetylation levels of the glycolytic enzymes in meat, including glycogen phosphorylase, phosphofructokinase, aldolase (ALDOA), triose-phosphate isomerase (TPI1), phosphoglycerate kinase, lactate dehydrogenase (LDH). The samples were assigned into three groups: Control, Chilling 1 and Chilling 2, corresponding to the chilling rates of 4.8 °C/h, 23.0 °C/h and 25.1 °C/h respectively. The contents of glycogen and ATP were significantly higher in samples from the chilling groups. The activity and phosphorylation level of the six enzymes were higher in samples at the chilling rate of 25.1 °C/h, while the acetylation level of ALDOA, TPI1 and LDH were inhibited. In brief, glycolysis was delayed and the activity of glycolytic enzymes were maintained at higher level by the changes of phosphorylation and acetylation levels at the chilling rates of 23.0 °C/h and 25.1 °C/h, which may partly explain why very fast chilling improves meat quality.
•Muscle fiber area and density in scallops is in relation to texture parameters of the striated and smooth adductor muscles.•A total of 743 different phosphoproteins have been revealed between the ...striated and smooth adductor muscles.•The unique phosphorylation sites of glycolytic enzymes have been identified in the striated adductor muscle.•The findings will provide new evidences on the role of muscle structure and protein phosphorylation in scallop meat quality.
Many proteins are known to be phosphorylated, affecting important regulatory factors of muscle quality in the aquatic animals. The striated and smooth adductor muscles of Yesso scallop Patinopecten yessoensis were used to investigate muscle texture and identify phosphoproteins by histological methods and phosphoproteomic analysis. Our present study reveals that muscle fiber density is in relation to meat texture of the striated and smooth adductor muscles. The phosphoproteomic analysis has identified 764 down-regulated and 569 up-regulated phosphosites on 743 phosphoproteins in the smooth muscle compared to the striated part. The identification of unique phosphorylation sites in glycolytic enzymes may increase the activity of glycolytic enzymes and the rate of glycolysis in the striated adductor muscle. The present findings will provide new evidences on the role of muscle structure and protein phosphorylation in scallop muscle quality and thus help to develop strategies for improving meat quality of scallop products.
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