Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.1.1 (hexokinase)
5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human erythrocytes overloaded with glucose 1,6-bisphosphate were prepared in order to establish the metabolic significance of this phosphorylated sugar in the intact red cell. The intracellular glucose 1,6-bisphosphate concentration was increased six- and twofold over the normal level by encapsulating (i) the commercially available compound and (ii) the glucose 1,6-bisphosphate synthase obtained from rabbit skeletal muscle, respectively. In both experimental conditions, a reduction of glucose utilization by the loaded cells was observed after reequilibration to the steady state. At the steady state, the concentrations of the glycolytic intermediates and of the adenine nucleotides appeared substantially unmodified when compared with those of controls, with the exception of a 50% reduction of glucose and fructose 6-phosphate measured in erythrocytes encapsulated with exogenous glucose 1,6-bisphosphate. Under the considered experimental conditions, the elevated intracellular glucose 1,6-bisphosphate appears to display an inhibitory effect on hexokinase that overcomes the possible activation of phosphofructokinase or pyruvate kinase.
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PMID:Glucose 1,6-bisphosphate-overloaded erythrocytes: a strategy to investigate the metabolic role of the bisphosphate in red blood cells. 130 80

The purpose of the present study was to determine the effects of low-frequency electrical stimulation (LFES) on the skeletal muscle metabolic profile of men and women. The knee extensor muscles of sedentary men (N = 16) and women (N = 10) were submitted to 3 h.d-1 of 8-Hz neuromuscular electrical stimulation with the use of a portable stimulator (Respond II, Medtronic), 6 d.wk-1 for 6 wk. Enzyme activity levels of creatine kinase (CK), hexokinase (HK), glyceraldehydephosphate dehydrogenase (GAPDH), 3-hydroxyacyl CoA dehydrogenase (HADH), citrate synthase (CS), phosphofructokinase (PFK), and cytochrome c oxidase (COX) were determined in vastus lateralis muscle samples taken before and after the LFES protocol. The analyses of variance revealed no change in CK and in GAPDH. However, a small decrease in PFK activity, the rate-limiting enzyme of glycolysis, was observed in female (8%) and in male subjects (10%), but it reached significance in males only (P < 0.05). The activity level of HK, a regulatory enzyme of the skeletal muscle glucose phosphorylation (HK), increased significantly in female subjects only (36%; P < 0.01) in response to the stimulation protocol. Activity level of marker enzymes of the Krebs cycle (CS) and of the electron-transfert chain (COX) significantly increased in males (18% and 16%; P < 0.05) as well as in females (31% and 19%; P < 0.05). Increment in the marker enzyme activity of the fatty acid oxidation (HADH) was significant in female subjects (30%; P < 0.01) and, although significant, rather modest in male subjects (12%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electrical stimulation-induced changes in skeletal muscle enzymes of men and women. 133 93

There are important differences between the short- and long-term effects of adrenaline on determinants of glucose tolerance. To assess this metabolic adaptation at tissue level, the present study examined the effect of acute and prolonged in vivo elevation of adrenaline on glycogen metabolism and glycolysis in skeletal muscle. Adrenaline (50 ng.kg-1.min-1) was infused for 2 h or 74 h and the results compared with 1 h 0.9% NaCl infusion in six trained dogs. Muscle glycogen content was reduced by long-term adrenaline (161 +/- 17 vs NaCl 250 +/- 24 mumol/g dry weight; p less than 0.05) but not short-term adrenaline (233 +/- 21) indicating a sustained effect of adrenaline on glycogen metabolism. Acutely, glycogen synthase I was reduced (short-term adrenaline 12 +/- 6 vs NaCl 22 +/- 7 mumol glycosyl units.g-1.min-1; p less than 0.05) but returned to normal with prolonged adrenaline infusion (20 +/- 5). In contrast, Km for glycogen phosphorylase alpha was not changed acutely (short-term adrenaline 31 +/- 6 vs NaCl 27 +/- 7 mmol/l inorganic phosphate) but was reduced during long-term infusion (19 +/- 4; p less than 0.05 vs short-term adrenaline). Thus, with short- and long-term adrenaline infusion, there were different enzyme changes, although likely to promote glycogenolysis in both cases. In the glycolytic pathway the substrates glucose 6-phosphate and fructose 6-phosphate did not change significantly and hexokinase was not inhibited. Acutely, phosphofructokinase had reduced Vmax (short-term adrenaline 34 +/- 6 vs NaCl 44 +/- 5 U/g; p less than 0.05) but was still above the maximal operating rate in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contrasting action of short- and long-term adrenaline infusion on dog skeletal muscle glucose metabolism. 138 57

Selected enzymes of energy metabolism were measured in random individual fibers of soleus and tibialis anterior (TA) muscles from rats exposed for 2 wk to spaceflight (F) aboard COSMOS 2044 or tail suspension (T) and from synchronous controls. Average size of soleus fibers (dry weight per unit length) was reduced 37% in F and T fibers; there was little change in TA fibers. Enzyme changes were more pronounced in soleus than in TA fibers. Three enzymes characteristic of fast-twitch muscles, pyruvate kinase, glycerol-3-phosphate dehydrogenase, and 1-phosphofructokinase, were elevated in F and T soleus fibers, but changes in phosphofructokinase were not statistically significant. 3-Ketoacid-CoA transferase, characteristic of slow-twitch muscles, did not change significantly in either F or T fibers. Hexokinase, usually moderately higher in slow- than in fast-twitch muscles, increased markedly in both F and T fibers. In TA fibers analyzed for hexokinase, malate dehydrogenase, phosphohexoisomerase, and pyruvate kinase, only hexokinase and malate dehydrogenase showed significant changes. Hexokinase increased 83% in one of two T muscles. Enzyme data for TA fibers typed by myosin adenosinetriphosphatase were more informative: phosphofructokinase, phosphorylase, and glycerol-3-phosphate dehydrogenase were increased in type IIb fibers of either F or T muscles or both. Malate dehydrogenase was not changed in fibers of any type in either F or T muscle.
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PMID:Effects of microgravity and tail suspension on enzymes of individual soleus and tibialis anterior fibers. 138 50

1. Time-curves of insulin effects on energy-producing systems in different cellular compartments of rat diaphragm muscle have revealed: (a) a rapid (within minutes) and transient stimulatory effect of insulin on cytoskeletal phosphofructokinase and aldolase and mitochondrial hexokinase. (b) A slower and consistent stimulatory effect on glucose 1,6-bisphosphate level, with concomitant gradual activation of cytosolic phosphofructokinase. Fructose 2,6-bisphosphate levels were not changed by insulin. (c) Lactate concentration correlated with the stimulation of cytoskeletal and cytosolic glycolysis. 2. Calmodulin antagonists, trifluoperazine or CGS 9343B, prevented all these effects of insulin. 3. These results suggest that cytoskeletal glycolysis and mitochondrial oxidation are the source of ATP for the rapid actions of insulin, whereas cytosolic glycolysis is the source of ATP for the slow actions of insulin. Calmodulin is involved in all these effects of insulin.
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PMID:Sequence of insulin effects on cytoskeletal and cytosolic phosphofructokinase, mitochondrial hexokinase, glucose 1,6-bisphosphate and fructose 2,6-bisphosphate levels, and the antagonistic action of calmodulin inhibitors, in diaphragm muscle. 139 93

The consumption of glucose by trypanosomatid protozoa such as Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., and Crithidia spp. is characterized by the excretion of reduced products such as succinate, pyruvate, ethanol, L-alanine, or lactate (depending on the species) not only in anaerobiosis, but also under aerobic conditions. The "aerobic fermentation" of glucose is accompanied by a complete lack, or even a reversal, of the Pasteur effect. This peculiar catabolism is mediated by a so-far unique compartmentation of the glycolytic enzymes, most of which are placed in an organelle called the glycosome; by an almost complete lack of inhibitory controls at the level of hexokinase and phosphofructokinase; and by a central role of CO2 fixation through the reaction catalyzed by phosphoenolpyruvate carboxykinase. The production of fermentative products seems to be due to a relative inefficiency of the respiratory chain, which lacks NADH dehydrogenase and the first phosphorylation site and preferentially uses succinate as substrate.
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PMID:Aerobic fermentation of glucose by trypanosomatids. 139 37

Various strategies to improve the therapeutic index of anticancer agents aim at inducing, by stimulation of aerobic glycolysis, temporary pH differences between malignant and normal tissues which can be exploited to activate cytotoxic agents selectively in tumors. We have investigated whether the pH reduction induced by glucose, the "drug" commonly used to increase lactic acid production in malignant tissues, can be augmented by pharmacological manipulation of tumor cell glycolysis. At normal plasma glucose concentration (6 +/- 1 mM), inorganic phosphate, a modifier of hexokinase and phosphofructokinase activity, had no effect on pH in two transplanted rat tumors and a human tumor xenograft line (average pH, 6.80; range, 6.65-6.95). When plasma glucose concentration was raised to 30 +/- 3 mM by i.v. infusion of glucose, inorganic phosphate reduced the pH in those tumors which exhibited only a moderate pH response to glucose per se (mean pH, 6.60) to an average value of 6.20 (range, 6.05-6.35). In the same setting, insulin, continuously infused at dose rates up to 600 milliunits/kg body weight/min, did not result in acidification of tumor tissue exceeding that induced by glucose alone. However, the H+ ion activity in both transplanted rat tumors and human tumor xenografts was increased by m-iodobenzylguanidine (MIBG), an inhibitor of mitochondrial respiration. For example, at normoglycemia, MIBG reduced the mean pH in a human mesothelioma xenograft from 6.90 to 6.70. This pH value was further reduced to 6.20 by simultaneous low-dose i.v. glucose infusion (plasma glucose concentration, 14 +/- 3 mM). The acidosis induced by inorganic phosphate and MIBG was tumor specific. Normal tissues of tumor-bearing hosts were only marginally sensitive to hyperphosphatemia or MIBG administration. These results indicate that the known stimulatory effect of exogenous glucose on lactic acid production in malignant tumors in vivo can be further accentuated or, as in the case of MIBG, partially replaced by pharmacological manipulation of aerobic glycolysis using clinically established drugs.
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PMID:pH in human tumor xenografts and transplanted rat tumors: effect of insulin, inorganic phosphate, and m-iodobenzylguanidine. 142 63

Erythrocytes from young type I diabetic patients (n = 11), incubated in their plasma in anaerobic conditions, exhibited higher glucose consumption than cells from controls (n = 11). This increased metabolic activity is believed to reflect erythrocyte alterations dependent on the degree of metabolic control, as glucose consumption was significantly correlated to glycosylated haemoglobin (HbA1) and to glucose levels (P < 0.05 and P < 0.01 respectively). Red cell hexokinase (HK) and pyruvate kinase (PK) activities were similar in both groups whereas phosphofructokinase (PFK) activity was slightly higher in patients' cells (P < 0.05). No difference was found between patients and controls for red cell ATP and 2.3 diphosphoglycerate (2.3 DPG) levels. However, the concentrations of these glycolytic products seem also closely related to the glucose homeostasis in diabetes. Indeed, within the diabetic group, ATP levels showed a negative relationship with glucose level (P < 0.05) and 2.3 DPG a positive relationship with HbA1 (P < 0.05). In conclusion, higher glycolytic activity is present in young diabetic red cells. This activity as well as ATP and 2.3 DPG levels are related to the degree of short- or long-term diabetic control. These findings stress the importance of a careful metabolic control to avoid haematological disturbances.
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PMID:Erythrocyte metabolic alterations in type I diabetes: relationship to metabolic control. 144 91

Enzyme activities were determined quantitatively in individual rat oocytes to study their energy metabolism during maturation. Low hexokinase activity and high activities of lactate dehydrogenase and enzymes in the phosphate pathway, i.e., glucose 6-P and 6-P gluconate dehydrogenases, were characteristic of immature oocytes. Hexokinase may be a rate-limiting enzyme that enables oocytes to use glucose as an energy source. During maturation, the activities of hexokinase, phosphofructokinase, and malate dehydrogenase increased significantly, suggesting that the glycolytic pathway, as well as the tricarboxylic acid cycle, developed as the first meiotic division proceeded. In contrast, the activities of glucose 6-P and 6-P gluconate dehydrogenases decreased in maturing oocytes. The observation that the enzyme pattern in mature oocytes resembles more closely that in somatic cells appears to be significant, especially in light of previous studies showing this developmental trend in preimplantation embryos.
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PMID:Determination of enzyme activities of energy metabolism in the maturing rat oocyte. 144

mRNA steady-state levels and activities of enzymes of intermediary carbon metabolism (hexokinase, phosphoglucoisomerase, phosphofructokinase, glucose-6-phosphate dehydrogenase, phosphoglucomutase) and glucose-regulated enzymes (pyruvate decarboxylase, pyruvate dehydrogenase, invertase, alcohol dehydrogenase) were determined in glucose-limited continuous cultures of an industrial strain of Saccharomyces cerevisiae at different dilution rates (D) ranging from 0.05 to 0.315 h-1. The activity of most enzymes measured remained constant over this range except for alcohol dehydrogenase I/II which decreased proportionally with increasing dilution rate. A decrease in phosphoglucomutase activity occurred with increasing dilution rate but reached a minimum at D 0.2 h-1 and from thereon remained constant. A decrease in pyruvate decarboxylase activity and a slight decrease in phosphoglucoisomerase activity was observed. At D 0.29/0.315 h-1, at the onset of the Crabtree effect, most glycolytic enzymes remained constant except for pyruvate decarboxylase and glucose-6-phosphate dehydrogenase which increased at D 0.315 h-1 and alcohol dehydrogenase I/II which decreased. The ADHI/II and PDC1 mRNA levels obtained at the different dilution rates were in accordance with the activity measurements. The mRNA level of HXK1 decreased with increasing dilution rates, whereas the transcription of HXK2 increased. Pyruvate dehydrogenase (PDA1) and PGI1 mRNA fluctuated but no significant change could be detected. These results indicate that there is no transcriptional or translational regulation of glycolytic flux between D 0.05 h-1 and 0.315 h-1 except at the branch point between oxidative and fermentative metabolism (pyruvate decarboxylase/pyruvate dehydrogenase) at D 0.315 h-1. Surprisingly regulation of the Crabtree effect does not seem to involve transcriptional regulation of PDA1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of transcription and translation of glycolytic enzymes in glucose-limited continuous cultures of Saccharomyces cerevisiae. 148 26


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