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)

This review focuses on the mechanisms of control of heart glycolysis under conditions of normal and reduced oxygen supply. The kinetic properties and the biochemical characteristics of control steps (glucose transporters, hexokinase, glycogen phosphorylase and phosphofructokinases) in the heart are reviewed in the light of recent findings and are considered together to explain the control of glycolysis by substrate supply and availability, energy demand, oxygen deprivation and hormones. The role of fructose 2,6-bisphosphate in the control of glycolysis is analysed in detail. This regulator participates in the stimulation of heart glycolysis in response to glucose, workload, insulin and adrenaline, and it decreases the glycolytic flux when alternative fuels are oxidized. Fructose 2,6-bisphosphate integrates information from various metabolic and signalling pathways and acts as a glycolytic signal. Moreover, a hierarchy in the control of glycolysis occurs and is evidenced in the presence of adrenaline or cyclic AMP, which relieve the inhibition of glycolysis by alternative fuels and stimulate fatty acid oxidation. Insulin and glucose also stimulate glycolysis, but inhibit fatty acid oxidation. The mechanisms of control underlying this fuel selection are discussed. Finally, the study of the metabolic adaptation of glucose metabolism to oxygen deprivation revealed the implication of nitric oxide and cyclic GMP in the control of heart glucose metabolism.
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PMID:Mechanisms of control of heart glycolysis. 987 92

The present study was carried out to assess the effect of chronic dichlorvos exposure on various aspects of glucose homeostasis in different regions of rat brain. Dichlorvos administration caused a significant depletion in the brain glycogen content accompanied with an increase in the activity of glycogen phosphorylase. The activities of key glycolytic enzymes, hexokinase, phosphofructokinase and lactate dehydrogenase were decreased significantly following dichlorvos exposure. The decreased glycolytic flux was further reflected in terms of decreased regional glucose utilization, determined by measuring 14C-glucose influx. The altered neuronal glucose homeostasis had a significant impact on the neurobehavioural patterns of dichlorvos treated animals which was reflected in terms of severe deterioration in their memory and learning functions.
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PMID:Dichlorvos induced alterations in glucose homeostasis: possible implications on the state of neuronal function in rats. 1054 56

Increased activity of hepatic glucose phosphorylation was observed in perch after feeding previously fasted fish. When a pellet diet containing 14% carbohydrate was given, most of the increased activity had a low affinity towards glucose (S0.5 = 19.5 mM) and resembled the mammalian glucokinase (Hexokinase IV or D) and the glucokinase-like activity previously observed in salmon liver. In addition, increased activity of a hexokinase with high affinity towards glucose (Km = 0.50 mM) was observed with the pellet diet. An increase in the activity of this hexokinase alone was observed when the fish were fed with filet of cod containing less than 0.2% carbohydrate. Perch with a very high hepatic glucokinase-like activity after eating the pellet diet had high activities of pyruvate kinase and glucose-6-phosphate dehydrogenase, indicating a high capacity of glycolysis and carbohydrate utilization. Simultaneously, the activity of glycogen phosphorylase was strongly reduced while the activity of fructose-1,6-bisphosphatase was not significantly changed. These observations were made with perch captured in the spawning season and brought to the laboratory. Assays of glucose phosphorylation in livers of perch eating the natural diet (insects) in the lake showed no glucokinase-like activity.
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PMID:Hepatic glucose phosphorylating activities in perch (Perca fluviatilis) after different dietary treatments. 1081 72

Selective breeding is an important tool in behavioral genetics and evolutionary physiology, but it has rarely been applied to the study of exercise physiology. We are using artificial selection for increased wheel-running behavior to study the correlated evolution of locomotor activity and physiological determinants of exercise capacity in house mice. We studied enzyme activities and their response to voluntary wheel running in mixed hindlimb muscles of mice from generation 14, at which time individuals from selected lines ran more than twice as many revolutions per day as those from control (unselected) lines. Beginning at weaning and for 8 wk, we housed mice from each of four replicate selected lines and four replicate control lines with access to wheels that were free to rotate (wheel-access group) or locked (sedentary group). Among sedentary animals, mice from selected lines did not exhibit a general increase in aerobic capacities: no mitochondrial [except pyruvate dehydrogenase (PDH)] or glycolytic enzyme activity was significantly (P < 0.05) higher than in control mice. Sedentary mice from the selected lines exhibited a trend for higher muscle aerobic capacities, as indicated by higher levels of mitochondrial (cytochrome-c oxidase, carnitine palmitoyltransferase, citrate synthase, and PDH) and glycolytic (hexokinase and phosphofructokinase) enzymes, with concomitant lower anaerobic capacities, as indicated by lactate dehydrogenase (especially in male mice). Consistent with previous studies of endurance training in rats via voluntary wheel running or forced treadmill exercise, cytochrome-c oxidase, citrate synthase, and carnitine palmitoyltransferase activity increased in the wheel-access groups for both genders; hexokinase also increased in both genders. Some enzymes showed gender-specific responses: PDH and lactate dehydrogenase increased in wheel-access male but not female mice, and glycogen phosphorylase decreased in female but not in male mice. Two-way analysis of covariance revealed significant interactions between line type and activity group; for several enzymes, activities showed greater changes in mice from selected lines, presumably because such mice ran more revolutions per day and at greater velocities. Thus genetic selection for increased voluntary wheel running did not reduce the capability of muscle aerobic capacity to respond to training.
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PMID:Effects of voluntary activity and genetic selection on muscle metabolic capacities in house mice Mus domesticus. 1100 2

Glycolytic fibres in rat extensor digitorum longus (EDL) and tibialis anterior (TA) were selectively activated, as demonstrated by glycogen depletion, by indirect electrical stimulation via electrodes implanted in the vicinity of the peroneal nerve using high frequency (40 Hz) trains (250 ms at 1 Hz) and low voltage (threshold of palpable contractions). This regime was applied 10 times per day, each bout being of 15 min duration with 60 min recovery, for 2 weeks. Cryostat sections of muscles were stained for alkaline phosphatase to depict capillaries, succinate dehydrogenase (SDH) to demonstrate oxidative fibres, and periodic acid-Schiff reagent (PAS) to verify glycogen depletion. Specific activity of hexokinase (HK), 6-phosphofructokinase, pyruvate kinase, glycogen phosphorylase and cytochrome c oxidase (COX) were estimated separately in homogenates of the EDL and the predominantly glycolytic cortex and oxidative core of the TA. Stimulation increased the activity of HK but not that of oxidative enzymes in fast muscles. Comparison of changes in oxidative capacity and capillary supply showed a dissociation in the predominantly glycolytic TA cortex. Here, COX was 3.9+/-0.68 microM min(-1) (g wet wt)-1 in stimulated muscles compared with 3.7+/-0.52 microM min(-1) (g wet wt)-1 in contralateral muscles (difference not significant), while the percentage of oxidative fibres (those positively stained for SDH) was also similar in stimulated (14.0+/-2.8 %) and contralateral (12.2 +/-1.9 %) muscles. In contrast, the capillary to fibre ratio was significantly increased (2.01+/-0.12 vs. 1.55+/-0.04, P<0.01). We conclude that capillary supply can be increased independently of oxidative capacity, possibly due to haemodynamic factors, and serves metabolite removal to a greater extent than substrate delivery.
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PMID:Selective long-term electrical stimulation of fast glycolytic fibres increases capillary supply but not oxidative enzyme activity in rat skeletal muscles. 1103 8

Glucose metabolism by Prevotella intermedia and Prevotella nigrescens were investigated. Glucose increased the anaerobic growth of these bacteria and promoted the accumulation of intracellular polysaccharide. The polysaccharide was confirmed to be glycogen-like glucan by the absorption spectrum of iodinepolysaccharide complex and the sugar composition. The washed cells consumed glucose anaerobically and converted a part of glucose into the metabolic end-products acetate, formate and succinate. The rest of glucose was confirmed to be accumulated as intracellular polysaccharide. The cells grown in the presence of glucose produced acetate, formate and succinate without exogenous glucose along with the consumption of intracellular polysaccharide. The metabolism of glucose and intracellular polysaccharide required bicarbonate. Prevotella cells had hexokinase and a set of the usual enzymes of the Embden-Meyerhof-Parnas pathway except that phosphofructokinase was pyrophosphate-dependent. A series of enzymes, including phosphoenolpyruvate carboxylase, phosphoenolpyruvate carboxykinase, malate dehydrogenase, fumarase and fumarate reductase, was found for succinate formation. Another series of enzymes, pyruvate oxidoreductase, pyruvate formate-lyase, phosphotransacetylase and acetate kinase was found for acetate and formate formation. Glucose 1,6-bisphosphate-dependent phosphoglucomutase and fructose 1,6-bisphosphate-activated UDP-glucose pyrophosphorylase were detected for glycogen synthesis, while glycogen phosphorylase was for glycogen degradation. The capacity of intracellular polysaccharide formation in addition to glucose fermentation could be advantageous for survival in the supragingival area as well as in the subgingival area.
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PMID:Glucose metabolism by Prevotella intermedia and Prevotella nigrescens. 1115 2

We evaluated the effect of sodium molybdate on carbohydrate metabolizing enzymes and mitochondrial enzymes in diabetic rats. Diabetic rats showed a significant reduction in the activities of glucose metabolising enzymes like hexokinase, glucose-6-phosphate dehydrogenase, glycogen synthase and in the level of glycogen. An elevation in the activities of aldolase, glucose-6-phosphatase, fructose 1,6- bisphosphatase, glycogen phosphorylase and in the level of blood glucose were also observed in diabetic rats when compared to control rats. The activities of mitochondrial enzymes isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH-dehydrogenase and cytochrome-C-oxidase were also significantly lowered in diabetic rats. Molybdate administration to diabetic rats reversed the above changes in a significant manner. From our observations, we conclude that administration of sodium molybdate regulated the blood sugar levels in alloxan-induced diabetic rats. Sodium molybdate therapy not only maintained the blood glucose homeostasis but also altered the activities of carbohydrate metabolising enzymes. Molybdate therapy also considerably improved the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.
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PMID:Effect of sodium molybdate on carbohydrate metabolizing enzymes in alloxan-induced diabetic rats. 1183 16

After 14 generations of selection for voluntary wheel running, mice from the four replicate selected lines ran, on average, twice as many revolutions per day as those from the four unselected control lines. To examine whether the selected lines followed distinct strategies in the correlated responses of the size and metabolic capacities of the hindlimb muscles, we examined mice from selected lines, housed for 8 wk in cages with access to running wheels that were either free to rotate ("wheel access" group) or locked ("sedentary"). Thirteen of twenty individuals in one selected line (line 6) and two of twenty in another (line 3) showed a marked reduction ( approximately 50%) in total hindlimb muscle mass, consistent with the previously described expression of a small-muscle phenotype. Individuals with these "mini-muscles" were not significantly smaller in total body mass compared with line-mates with normal-sized muscles. Access to free wheels did not affect the relative mass of the mini-muscles, but did result in typical mammalian training effects for mitochondrial enzyme activities. Individuals with mini-muscles showed a higher mass-specific muscle aerobic capacity as revealed by the maximal in vitro rates of citrate synthase and cytochrome c oxidase. Moreover, these mice showed the highest activities of hexokinase and carnitine palmitoyl transferase. Females with mini-muscles showed the highest levels of phosphofructokinase, and males with mini-muscles the highest levels of pyruvate dehydrogenase. As shown by total muscle enzyme contents, the increase in mass-specific aerobic capacity almost completely compensated for the reduction caused by the "loss" of muscle mass. Moreover, the mini-muscle mice exhibited the lowest contents of lactate dehydrogenase and glycogen phosphorylase. Interestingly, metabolic capacities of mini-muscled mice resemble those of muscles after endurance training. Overall, our results demonstrate that during selection for voluntary wheel running, distinct adaptive paths that differentially exploit the genetic variation in morphological and physiological traits have been followed.
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PMID:Artificial selection for high activity favors mighty mini-muscles in house mice. 1252 84

The effect of the administration of blackgram fiber (Phaseolus mungo) on the metabolism of carbohydrates was studied in rats fed 30% NDF (neutral detergent fiber) diet. The experimental group showed a significant increase in liver glycogen level and a significant decrease in blood glucose. Significant increases in the activities of glycogen phosphorylase, hexokinase, fructose-1, 6-diphosphatase, glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase were observed in the experimental group. The activities of phosphoglucomutase and glucose-6-phosphatase were significantly lower in rats fed the fiber diet. The study showed that blackgram fiber exhibits significant hypoglycemic action in experimental animals.
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PMID:Blackgram fiber (Phaseolus mungo): mechanism of hypoglycemic action. 1285 9

At the onset of exercise, signals from inside and outside the muscle cell increase the availability of carbohydrate (CHO) and fat to provide the fuel required for ATP production. CHO and fat oxidation are the dominant sources of aerobic ATP production and both pathways must be heavily upregulated during exercise to meet the increased energy demand. Within this paradigm, there is room for shifts between the proportion of energy that is provided from CHO and fat. It has long been known that increasing the availability of endogenous or exogenous CHO can increase the oxidation of CHO and decrease the oxidation of fat. The opposite is also true. While descriptive studies documenting these changes are numerous, the mechanisms regulating these shifts in fuel use in the face of constant energy demand have not been thoroughly elucidated. It would be expected, for example, that any fat-induced shift in CHO metabolism would target the enzymes that play key roles in regulating CHO metabolism and oxidation. Inside the muscle these could include glucose uptake (GLUT4) and phosphorylation (hexokinase), glycogenolysis (glycogen phosphorylase), glycolysis (phosphofructokinase) and conversion to acetyl CoA (pyruvate dehydrogenase). The same would be expected for a CHO-induced down regulation of fat metabolism and oxidation and might target transport of long chain fatty acids into the cell (fatty acid translocase CD36), release of fatty acids from intramuscular triacylglycerol (hormone sensitive lipase) and transport into the mitochondria (carnitine palmitoyl transferase complex). This review summarizes the work describing the interaction between CHO and fat metabolism in human skeletal muscle during exercise and presents the theories that may account for CHO/fat interaction during exercise.
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PMID:Regulatory mechanisms in the interaction between carbohydrate and lipid oxidation during exercise. 1286 50


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