Energy metabolism is significantly reprogrammed in many human cancers, and these alterations confer many advantages to cancer cells, including the promotion of biosynthesis, ATP generation, detoxification and support of rapid proliferation. The pentose phosphate pathway (PPP) is a major pathway for glucose catabolism. The PPP directs glucose flux to its oxidative branch and produces a reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), an essential reductant in anabolic processes. It has become clear that the PPP plays a critical role in regulating cancer cell growth by supplying cells with not only ribose-5-phosphate but also NADPH for detoxification of intracellular reactive oxygen species, reductive biosynthesis and ribose biogenesis. Thus, alteration of the PPP contributes directly to cell proliferation, survival and senescence. Furthermore, recent studies have shown that the PPP is regulated oncogenically and/or metabolically by numerous factors, including tumor suppressors, oncoproteins and intracellular metabolites. Dysregulation of PPP flux dramatically impacts cancer growth and survival. Therefore, a better understanding of how the PPP is reprogrammed and the mechanism underlying the balance between glycolysis and PPP flux in cancer will be valuable in developing therapeutic strategies targeting this pathway.
Animals ; Energy Metabolism ; Glucose ; metabolism ; Glycolysis ; Humans ; Neoplasms ; metabolism ; pathology ; Pentose Phosphate Pathway ; physiology

The pancreatic islet beta-cell is uniquely specialized to couple its metabolism and rates of insulin secretion with the levels of circulating nutrient fuels, with the mitochondrial playing a central regulatory role in this process. In the beta-cell, mitochondrial activation generates an integrated signal reflecting rates of oxidativephosphorylation, Kreb's cycle flux, and anaplerosis that ultimately determines the rate of insulin exocytosis. Mitochondrial activation can be regulated by proton leak and mediated by UCP2, and by alkalinization to utilize the pH gradient to drive substrate and ion transport. Converging lines of evidence support the hypothesis that substrate cycles driven by rates of Kreb's cycle flux and by anaplerosis play an integral role in coupling responsive changes in mitochondrial metabolism with insulin secretion. The components and mechanisms that account for the integrated signal of ATP production, substrate cycling, the regulation of cellular redox state, and the production of other secondary signaling intermediates are operative in both rodent and human islet beta-cells.
Adenosine Triphosphate ; Cytosol ; Exocytosis ; Humans ; Insulin ; Ion Transport ; Islets of Langerhans ; Mitochondria ; Oxidation-Reduction ; Proton-Motive Force ; Protons ; Rodentia ; Substrate Cycling

A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells. Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool. ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis. In the present study, we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells. High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: glycolysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. ME1-repressed cells had significantly decreased tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress. Furthermore, diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein. Collectively, these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.
Carcinoma ; Cell Line, Tumor ; Cell Movement ; Cell Survival ; Glucose ; metabolism ; Glycolysis ; Humans ; Malate Dehydrogenase ; metabolism ; NADP ; metabolism ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Oxidation-Reduction ; Oxidative Phosphorylation ; Pentose Phosphate Pathway ; Proto-Oncogene Proteins c-akt ; metabolism

Metabolic reprogramming, such as abnormal utilization of glucose, addiction to glutamine, and increased de-novo lipid synthesis, extensively occurs in proliferating cancer cells, but the underneath rationale has remained to be elucidated. Based on the concept of the degree of reduction of a compound, we have recently proposed a calculation termed as potential of electron transfer (PET), which is used to characterize the degree of electron redistribution coupled with metabolic transformations. When this calculation is combined with the assumed model of electron balance in a cellular context, the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism. Some interesting properties of PET in cancer cells were also discussed, and the model was extended to uncover the chemical nature underlying aerobic glycolysis that essentially results from energy requirement and electron balance. Enabling electron transfer could drive metabolic reprogramming in cancer metabolism. Therefore, the concept and model established on electron transfer could guide the treatment strategies of tumors and future studies on cellular metabolism.
Electrons ; Energy Metabolism ; Glucose ; Glycolysis ; Humans ; Neoplasms

The evolutionary transition from single cells to the metazoan forced the appearance of adult stem cells and a hypoxic niche, when oxygenation of the environment forced the appearance of oxidative phosphorylation from that of glycolysis. The prevailing paradigm in the cancer field is that cancers start from the "immortalization" or "re-programming" of a normal, differentiated cell with many mitochondria, that metabolize via oxidative phosphorylation. This paradigm has been challenged with one that assumes that the target cell for carcinogenesis is the normal, immortal adult stem cell, with few mitochondria. This adult organ-specific stem cell is blocked from "mortalizing" or from "programming" to be terminally differentiated. Two hypotheses have been offered to explain cancers, namely, the "stem cell theory" and the "de-differentiation" or "re-programming" theory. This Commentary postulates that the paleochemistry of the oceans, which, initially, provided conditions for life's energy to arise via glycolysis, changed to oxidative phosphorylation for life's processes. In doing so, stem cells evolved, within hypoxic niches, to protect the species germinal and somatic genomes. This Commentary provides support for the "stem cell theory", in that cancer cells, which, unlike differentiated cells, have few mitochondria and metabolize via glycolysis. The major argument against the "de-differentiation theory" is that, if re-programming of a differentiated cell to an "induced pluri-potent stem cell" happened in an adult, teratomas, rather than carcinomas, should be the result.
Adult ; Adult Stem Cells ; Energy Metabolism ; Genome ; Glycolysis ; Humans ; Mitochondria ; Oceans and Seas ; Oxidative Phosphorylation ; Oxygen ; Stem Cells ; Teratoma

Dissimilatory Metal Reduction Bacteria play an important role in the anaerobic environment. This kind of bacteria gains energy by coupling the oxidation of organic acid or sugars to the reduction of metal oxides. The graphite electrode rode can also be used as the final electron acceptor due to its similarity to solid metal oxides. Based on this biological mechanism, Dissimilatory Metal Reduction Bacteria Rhodoferaxferrireducens was used to construct a suit of microbial fuel cells with sugars as fuel, and the process and mechanism of electricity generation was studied. Rhodoferax ferrireducens was inoculated into the anode chamber in which a graphite electrode served as the final electron acceptor and glucose as the sole electron donor. It was showed that current density was up to 158mA/m2 with the resistance of 510omega at the normal temperature (platform voltage was around 0.46V, the effectual electrode surface was 57cm2). Following 20days' growth a large amount of bacteria cells attached to the electrode surface had been observed through the SEM images. The plandtonic cell protein concentration was 140mg/L and the attached biomass of electrode surface was 1180mg/m2 determined by the Bradford method, which indicated quite a few bacteria attached to the electrode. By analyzing the voltage value measured by the data acquisition system, it was proved that microbial electricity generation attributed mainly to the electrochemically and biologically active cells attached to the electrode, while the planktonic cells had no ability to catalyze electricity generation and almost had not electrochemically and biologically active. Furthermore, this kind of microbial fuel cells exhibited a good electrochemical cycle property and proved to be efficient in biomass utilization and energy restore since other sugars like fructose, sucrose, even xylose, could be oxidized and finally decomposed. Vast waste biomass in the form of carbohydrates is discarded in the environment. Not only is contamination of the environment caused by the discarded biomass, but also abundant energy stored in the biomass is drained away in vain. The sugar-based microbial fuel cells constructed by Rhodoferax ferrireducens could effectively transform the energy stored in sugars into electricity. Meanwhile, the microbial fuel cells presented in this paper, which could work cleanly at normal temperature with a good cycle property, showed a promising future application in this field.
Bioelectric Energy Sources ; microbiology ; Comamonadaceae ; metabolism ; Electricity ; Electron Transport ; Equipment Failure ; Glucose ; metabolism ; Oxidation-Reduction

Pancreatic carcinoma is currently one of the most intractable malignant tumors of the digestive tract. Studies have found that the occurrence, progression and metastasis of pancreatic carcinoma are closely associated with the tumor's glycolytic pathway, most pancreatic carcinomas show the elevated glycolytic phenotype. To some extent, affecting the glycolytic pathway can influence the energy metabolism of the tumor without affecting the normal cells theoretically. Therefore, glycolytic pathway may become a new target for the treatment of pancreatic carcinoma.
Energy Metabolism ; Glycolysis ; Humans ; Pancreatic Neoplasms ; metabolism ; physiopathology

In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism. Hypoxic cancer cells use glucose for glycolytic metabolism and release lactate which is used by oxygenated cancer cells. This study challenged the Warburg effect, because Warburg claimed that fermentation by irreversible damaging of mitochondria is a fundamental cause of cancer. However, recent studies revealed that mitochondria in cancer cell show active function of oxidative phosphorylation although TCA cycle is stalled. It was also shown that blocking cytosolic NADH production by aldehyde dehydrogenase inhibition, combined with oxidative phosphorylation inhibition, resulted in up to 80% decrease of ATP production, which resulted in a significant regression of tumor growth in the NSCLC model. This suggests a new theory that NADH production in the cytosol plays a key role of ATP production through the mitochondrial electron transport chain in cancer cells, while NADH production is mostly occupied inside mitochondria in normal cells.
Adenosine Triphosphate ; Aldehyde Dehydrogenase ; Cytosol ; Electron Transport ; Energy Metabolism ; Fermentation ; Glucose ; Lactic Acid ; Metabolism ; Mitochondria ; NAD ; Oxidative Phosphorylation ; Oxygen ; Symbiosis

Basal metabolic rate (BMR) is of great significance to the setting of daily energy requirements and the scientific diet guidance for the population. There are 3 kinds of measurement methods for BMR, including the direct calorimetry, the indirect calorimetry, and the equation estimation. The direct calorimetry method is difficult to implement and is only used in some special populations. The indirect calorimetry and the equation estimation are two methods that are currently used commonly. The indirect calorimetry is highly accurate and suitable for individual for basal metabolic measurement or datum collection via equation estimation. The equation estimation is simple and convenient, which is suitable for large samples.
Basal Metabolism ; physiology ; Biomedical Research ; Calorimetry, Indirect ; Energy Metabolism ; Humans

Tumor cells have unique energy metabolism phenomena, namely high glucose absorption, aerobic glycolysis and high lactic acid production, which are characterized by down-regulation of related proteins involved in oxidative metabolism in tumor cells, and up-regulation of glucose transporters and monocarboxylate transporters. Studies have shown that drugs that target tumor cell glucose metabolism have the ability to selectively kill tumor cells, bringing new hope for tumor treatment. Tumor stem cells are considered to be the root cause of tumor recurrence, metastasis and poor prognosis, and their energy metabolism characteristics have not yet been agreed. Studies have shown that reversing the energy metabolism of tumor stem cells can increase their chemosensitivity. This article reviews recent studies on tumor and tumor stem cell glucose metabolism and the opportunities and challenges of tumor treatment through targeting glucose metabolism, which might provide new ideas and opportunities for clinical tumor therapy.
Energy Metabolism ; Glucose ; metabolism ; Glycolysis ; Humans ; Lactic Acid ; metabolism ; Neoplasms ; metabolism ; Neoplastic Stem Cells ; metabolism