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

Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through the identification of more pharmaceutically viable targets, and yet major problems and risks associated with late-phase cancer therapy remain. Presently, a growing number of reports have initiated a discussion about the benefits of metabolic regulation in cancers. The Warburg effect, a great discovery approximately 70 years ago, addresses the "universality" of cancer characteristics. For instance, most cancer cells prefer aerobic glycolysis instead of mitochondrial respiration. Recently, cancer metabolism has been explained not only by metabolites but also through modern molecular and chemical biological techniques. Scientists are seeking context-dependent universality among cancer types according to metabolic and enzymatic pathway signatures. This review presents current cancer metabolism studies and discusses future directions in cancer therapy targeting bio-energetics, bio-anabolism, and autophagy, emphasizing the important contribution of cancer metabolism in cancer therapy.
Autophagy ; Biology ; Glycolysis ; Metabolism* ; Molecular Biology ; Respiration ; Imatinib Mesylate

BACKGROUND: In our previous report, we observed the increaseed epidermal glucose concentrations and decreased hexokinase actiuities of diabetic patients which were ciimpared to those of normal individuals. And we considered that, there were some derrangement of lipid metabolism and glycolysis of diabetic epidermis. OBJECTIVES: This study wns planed to prove the above possible changes of lipid metabolism and glycolysis of diabetic epidermis. METHODS: The epidermal enzymatic activties of glucose-6-phophate dehydrogenase(G6PDH), phosphofructokinase(PFK), 1-glycerophosphate dehydrogenase(GOPDH) and b-hydroxybutyryl CoA dehydrogenase(HBDH) were assayed in the skin samples obtained friom diabetic patients and normal individuals by the fluorometric: method. RESULTS: Teh epidermal PFK activities of diabetic patients were decreased(3.49+1.35(mmole/hr/kg dry weight)) compared to that of normal individuals(5.00+0.56(mmcle/hr/kg dry weight))(p<0.05). The epidermal HBDH activities of diabetic patients were decreised(0.28+0.10(mole/hr/kg dry weight)) compared to that of normal individuals(0.49+0.20(mole/hr/kg dry weight)(p<0.01). The mean epidermal G6PDH activity of diabetic patients was decreasec. compased to that of normal individuals, but there was no statisical significance. The mean epidermal 3OPDH activittes of diabetic patients and normal individual; showed no significant difference. CONCLUSION: We consider that the decreased epidermal HBDH actiities of diabetic patients can decrease keton body formatiori, and the abnormal glycolysis can exist in the diabetic epidermis because the decreased enzymatic activities of diabetic epidermal PFK may decrease the velocity of glycolysis.
Diabetes Mellitus ; Epidermis ; Glucose ; Glycolysis ; Hexokinase ; Humans ; Lipid Metabolism ; Skin

Primary metabolic myopathy as a type of congenital myopathies was first described by McArdle in 1951. Glycogen storage disease is a disease caused by genetic mutations involved in glycogen synthesis, glycogenolysis or glycolysis. Several types of glycogen storage disease are known to cause metabolic myopathies. We report a case of adult onset metabolic myopathy with glycogen storage.
Adult* ; Glycogen Storage Disease ; Glycogen* ; Glycogenolysis ; Glycolysis ; Humans ; Muscular Diseases*

In anesthetized normocapnic and normotensive dogs, the effect of arterial hypoxemia on cerebral blood flow and oxidative carbohydrate metabolism was studied. The results are as follows: 1) The hypoxic vasodilatory effect on cerevral vessels is intact even at profound systemic hypoxemia(Pao2 30 torr) if Paco2 is controlled within normal limits. 2) CMRO2 did not significantly increase above the normal even during profound arterial hopoxemis, indicating that CMRO2 levels are poor indices of hypoxia. 3) A disporportinately high glycolysis at Pao2 of 50 torr suggested early cerebral metabolic changes which became more marked with further decrease in Pao2. 4) One hour after restitution of normoxia, however, carebral blood flow and metabolism manifested complete recovery. 6) It is concluded that a transient(20 minutes) profoun systemic arterial hypoxemia does not produce prolonged disorder of cerebral blood flow and oxidative carbohydrate metabolism provided that the cerebral perfusion pressure is kept normal.
Animals ; Anoxia* ; Carbohydrate Metabolism ; Cerebrovascular Circulation* ; Dogs ; Glycolysis ; Metabolism*

In order to understand metabolic functions essential for methane assimilation, we investigate dribulose monophosphate pathway and adjacent pathways in gammaproteobacterial Methylomicrobium alcaliphilum 20Z by using combined approaches of RNA-seq, LC-MS, and 13C-labeled techniques. The absolute quantification of metabolome showed that the concentrations of intermediates, such as glucose-6-phosphate and 2-dehydro-3-deoxy-phosphogluconate, involved in Entner-Doudoroff (EDD) pathway were (150.95 +/- 28.75) micromol/L and below the limit of detection of mass spectrometry. In contrast, fructose-1, 6-bisphosphate, glyceraldehyde-3-phosphate/dihydroxyacetone and phosphoenolpyruvate in Embden-Meyerhof-Parnas (EMP) pathway had significantly higher concentrations with (1 142.02 +/- 302.88) micromol/L, (1 866.76 +/- 388.55) micromol/L and (3 067.57 +/- 898.13) micromol/L, respectively. 13C-labeling experiment further indicated that the enrichment of [3-13C1]-pyruvate involved in EMP pathway was 4-6 fold higher than [1,13C1]-pyruvate in EDD pathway in a dynamic course. Moreover, gene expression profile showed that the expression levels of genes in EMP pathway (e.g. fbaA, tpiA, gap and pykA) were 2 479.2, 2 493.9, 2 274.6 and 1 846.0, respectively, but gene expressionlevels in EDD pathway (e.g. pgi, eda and edd) were only 263.8, 341.2 and 225.4, respectively. Overall our current results demonstrated that EMP pathway was the main route for methane assimilation in M. alcaliphilum 20Z. This discovery challenged our understanding of methane assimilation pathway in gammaproteobacterial methanotrophic bacteria, and further provided an important insight for efficient methane biocatalysis in the future.
Glycolysis ; Industrial Microbiology ; Methane ; metabolism ; Methylococcaceae ; metabolism ; Pyruvic Acid ; metabolism

OBJECTIVETo study the effect of methylene blue on the growth and acid production of Streptococcus mutans, and the effect of methylene blue on acid production metabolism in plaque glycolysis model (i-PGM) in vitro, and investigate the practicability of methylene blue as a new kind of dental caries prevention agent.

METHODSNephelometer method was used to measure OD value of Streptococcus mutans culture fluid in the different incubation conditions. The kinds and quantities of acid produced by Streptococcus mutans in the different incubation conditions were measured with gas chromatography. pH values of glycolysis buffer media of i-PGM in the different treatment conditions were measured by ORION electrode.

RESULTS(1) The OD value of Streptococcus mutans treated by methylene blue was lower than that by normal saline, and there was significant statistical difference between them. (2) The kinds of acid in three different culture fluid were same, but the total quantities of acid were significantly different among three different culture fluid, in which the total quantities of acid of culture fluids treated by glucose was the greatest, and treated by methylene blue was the lest. (3) The pH value of i-PGM treated by methylene blue was significantly different compared with negative control group, but was not significantly different compared with positive control group.

CONCLUSIONMethylene blue can inhibit the growth and acid production metabolism of Streptococcus matans and acid production metabolism of i-PGM.

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

PURPOSE: The urinary bladder requires an adequate energy supply to maintain contractile function. The primary metabolic fuel is glucose. Through glycolysis and oxidative phosphorylation, high energy phosphate are generated, which in turn supply the metabolic energy for the contractile activities of the urinary bladder. The aim of this study was to determine the effects of glucose deprivation and recovery from glucose deprivation on the phasic and tonic components of the contractile responses of rabbit bladder strips to field stimulation, bethanechol, and KCl. MATERIALS AND METHODS: The urinary bladder bodies of mature male New Zealand White rabbits were separated from the base above the level of the ureteral orifices, and placed in Tyrode`s solution containing glucose in 37degrees C and equilibrated with 95% O2 and 5% CO2. Bethanechol(250microM) was left in contact with the strips for 4 minutes. KCI(120 mM) was left in contact with the strips for 4 minutes. Field stimulation(31Hz, 80V, 1ms) was maintained for 2 minutes. At the end of each incubation in glucose-free medium(100 minutes for FS, 180 minutes for KCl and bethanechol), the medium was changed to Tyrode`s solution containing glucose(1mg/ml) and stimulations continued for additional 90 minutes. Changes in muscle tension were measured and recorded on a Grass model 7D polygraph. RESULTS: The results can be summarized as follow : In response to glucose deprivation, (1) the tonic responses to field stimulation, bethanechol, and KCl all decreased at a significantly greater rate than the phasic responses; (2) the phasic and tonic responses to field stimulation were both reduced to less than 10% of control within 70 minutes of glucose deprivation; (3) the tonic response to bethanechol and KCl were reduced to approximately 10% of control within 180 minutes whereas the phasic responses remained stable at 40 and 30%, respectively; and (4) glucose replacement stimulated a rapid and nearly complete recovery of the phasic and tonic components of the response to field stimulation, bethanechol, and KCl. Concolusions: These results indicate that the tonic responses to all forms of stimulation are more sensitive to glucose deprivation than phasic responses.
Bethanechol ; Glucose* ; Glycolysis ; Humans ; Male ; Muscle Tonus ; Oxidative Phosphorylation ; Poaceae ; Rabbits ; Ureter ; Urinary Bladder*

PURPOSE: To evaluate the predictive value of the early response of 18F-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT. RESULTS: One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of SUVmax (%DeltaSUVmax) were larger in responder group than in non-responder group (55.7% +/- 15.6% vs. 23.1% +/- 19.0%, p = 0.01). The percent changes of SUVmean (%DeltaSUVmean) were also larger in responder group than in non-responder group (54.4% +/- 15.9% vs. 22.3% +/- 23.0%, p = 0.01). The percent changes of MTV (%DeltaMTV) or TLG (%DeltaTLG) had no correlation with the tumor response after treatment. All the 7 patients (100%) with %DeltaSUVmax > or = 50% had PR, but only 2 out of 6 patients (33%) with %DeltaSUVmax < 50% had PR after CCRT (p = 0.009). Likewise, all the 6 patients (100%) with %DeltaSUVmean > or = 50% had PR, but only 3 out of 7 patients (43%) with %DeltaSUVmean < 50% had PR after CCRT (p = 0.026). CONCLUSION: The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.
Carcinoma, Non-Small-Cell Lung* ; Chemoradiotherapy* ; Glycolysis ; Humans ; Lung Neoplasms ; Positron-Emission Tomography ; Tumor Burden