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)

The effect of respiratory hypoxia on muscle glucose metabolism during short-term dynamic exercise has been investigated. Eight men cycled for 5 min at 120 +/- 6 W (mean +/- SE), which corresponded to 50% of maximal O2 uptake during normoxia (N), breathing air (N) on one occasion and 11% O2 (hypoxia-H) on the other. Biopsies were taken from the quadriceps femoris muscle before and after exercise. Oxygen uptake during exercise was not affected by H. The arterial blood glucose concentration during N exercise remained constant, but increased from 4.62 +/- 0.11 mmol l(-1) at rest to 5.22 +/- 0.19 mmol l-1 at the end of H exercise (P less than 0.05 vs N exercise). The intracellular glucose content at rest was low and did not change during N exercise, but was four times higher after exercise during H vs N (P less than 0.01). Glucose 6-P increased under both conditions but significantly more during H (P less than 0.01), while glucose 1,6-P2 was not significantly different between treatments either at rest or after exercise. It is concluded that: (1) glucose uptake by skeletal muscle during short-term exercise. It is concluded that: (1) glucose uptake by skeletal muscle during short-term exercise during H is not associated with a stoichiometric glucose utilization; (2) the inhibition of hexokinase during H (evidenced by increase in muscle glucose) is due primarily to the increase in glucose 6-P; and (3) glucose 1,6-P2 is of minor importance for the regulation of contraction-mediated flux through hexokinase in human skeletal muscle.
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PMID:Effect of hypoxia on glucose metabolism in human skeletal muscle during exercise. 275 May 38

1. The effect of hypocaloric feeding (25% of normal food intake for 21 days) of rats on the enzymic and metabolic adaptations in the gastrocnemius, plantaris and soleus muscles was studied. 2. In control and hypocaloric rats the muscle relaxation rates at 100 Hz were 35.76 and 11.38% force loss/10 ms respectively. Control rats exhibited enhanced force of muscle contraction as the frequency of stimulation increased from 10 to 100 Hz, with maximum force being at 100 Hz. Hypocaloric rats exhibited a decrease in the increment of force being exerted at high frequencies, with maintenance of force at lower stimulatory frequencies. 3. In muscles of hypocaloric rats, there were significant decreases in the maximal activities of hexokinase (17.6-37.0%), 6-phosphofructokinase (22.7-34.2%), pyruvate kinase (21.2-36.0%), citrate synthase (34.1-41.5%), oxoglutarate dehydrogenase (29.4-52.4%) and 3-hydroxyacyl-CoA dehydrogenase (26.7-32.1%), whereas the activities of glycogen phosphorylase increased (23.8-43.4%) compared with control values. 4. In soleus-muscle strip preparations of hypocaloric rats, there were significant decreases in the rates of lactate production (28.1%) and glucose oxidation (32.6%) compared with control preparations. 5. Mitochondrial preparations from muscles of hypocaloric rats incubated with various substrates exhibited decreased rates of oxygen uptake compared with control preparations. 6. In muscles of hypocaloric rats (gastrocnemius and soleus), there were significant decreases in the concentrations of glycogen (P less than 0.001) and phosphocreatine (P less than 0.001) and increases in those of pyruvate (P less than 0.001), lactate (P less than 0.001) and ADP (P less than 0.001), whereas those of ATP and AMP remained unchanged. 7. Calculated [lactate]/[pyruvate] and [ATP]/[ADP] ratios exhibited significant increases (P less than 0.05) and decreases (P less than 0.05) in muscles of hypocaloric rats respectively. 8. The results are discussed in relation to the genesis of muscle dysfunction caused by malnutrition.
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PMID:Enzymic and metabolic adaptations in the gastrocnemius, plantaris and soleus muscles of hypocaloric rats. 277 8

Based on the lack of correlation between the ability of various hexoses to serve as substrate and the ability of the corresponding hexose 6-phosphates to inhibit brain hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1), R. K. Crane and A. Sols (1954, J. Biol. Chem. 210, 597-606) proposed that this enzyme possesses two discrete sites capable of binding hexose moieties, one serving as the substrate binding site and a second, regulatory in function, to which inhibitory 6-phosphates bind. Subsequent work has provided further experimental support for this proposal. The pioneering work by Crane and Sols focused primarily on the specificity of these sites with respect to requirements for orientation of hydroxyl substituents at the various positions of the pyranose ring. The present study explores additional aspects of the specificity of these sites, namely, the effect of substitution of a sulfur atom in place of the oxygen in the pyranose ring on ability to serve as substrate or inhibitor, and the effect of modification in charge of the substituent at the 6-position on inhibitory effectiveness. 5-Thioglucose is a linear competitive (versus glucose) inhibitor of rat brain hexokinase, with a Ki of about 0.2 mM, and is a linear mixed inhibitor (versus ATP), with Ki values in this same range. 5-Thioglucose is not, however, readily phosphorylated by brain hexokinase. Thus, although 5-thioglucose binds with moderate affinity to the glucose binding site, it is not effectively used as a substrate of the enzyme. Inhibition of brain hexokinase by glucose 6-phosphate or its analogs has been found to require a dianionic substituent at the 6-position. The 6-fluorophosphate derivative and glucose 6-sulfate are poor inhibitors of the enzyme, and the Ki for inhibition by 1,5-anhydroglucitol 6-phosphate increases markedly at pH values below the pK of the 6-phosphate group, indicating that the monoanionic form is ineffective as an inhibitor. In contrast to the detrimental effect that substitution of the oxygen atom in the pyranose ring with a sulfur has on ability to serve as substrate, 5-thio analogs are considerably more effective as inhibitors, the Ki for inhibition by 5-thioglucose 6-phosphate being 10-fold lower than that seen with glucose 6-phosphate. This effect of the heteroatom substitution can partially offset the decreased inhibition resulting from monoanionic character at the 6-position, but the 6-fluorophosphate derivative of 5-thioglucose 6-phosphate still inhibits with a Ki about 1000-fold greater than that seen with 5-thioglucose 6-phosphate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Rat brain hexokinase: further studies on the specificity of the hexose and hexose 6-phosphate binding sites. 291 81

The erythrocyte metabolism of two patients with nonspherocytic hemolytic anemia caused by a hexokinase deficiency, and a pyruvate kinase deficiency, respectively, were studied with NMR. The complexing of ATP and 2,3-diphosphoglycerate (2,3-DPG) with Mg2+ and hemoglobin (Hb) was determined using 31P-NMR on oxygenated and deoxygenated cells to investigate the influences of these enzyme defects on intracellular magnesium distribution and on Hb oxygen dissociation. In the pyruvate kinase-deficient red blood cells, the 2,3-DPG concentration was almost twice the normal value and the ATP concentration was near the lower limit of the normal range. In the hexokinase-deficient red cell population, the predominance of young cells masked the deficiency. Therefore, reticulocyte control cells were included in this study. In the oxygenated pyruvate kinase-deficient cells, the fraction of ATP that is complexed to magnesium as well as the free Mg2+ concentration were normal, despite the abnormal concentration of 2,3-DPG. In the deoxygenated cells the free Mg2+ concentration was lower than in normal cells. The fraction of Hb complexed with 2,3-DPG was higher than normal in both oxygenated and deoxygenated pyruvate kinase-deficient cells, in accordance with the high p50 of the oxygen-hemoglobin dissociation curve. In hexokinase-deficient cells, two major abnormalities are found: when the cells were deoxygenated, the concentration of ATP and 2,3-DPG fell. This was not observed for any other sample and could, therefore, be a consequence of the hexokinase deficiency. Despite almost normal levels of magnesium-binding metabolites, the free Mg2+ concentration in oxygenated and deoxygenated cels is much lower than in normal cells. This could be a cell-age-related phenomenon, since lower free Mg2+ concentrations were also found in reticulocyte control cells.
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PMID:Intracellular free magnesium and phosphorylated metabolites in hexokinase- and pyruvate kinase-deficient red cells measured using 31P-NMR spectroscopy. 292 Jan 77

The rates of ATP synthesis and release by the dynein ATPase were determined in order to estimate thermodynamic parameters according to the pathway: (Formula: see text). Dynein was incubated with high concentrations of ADP and Pi to drive the net synthesis of ATP, and the rate of ATP production was monitored fluorometrically by production of NADPH through a coupled assay using hexokinase and glucose-6-phosphate dehydrogenase. The turnover number for the rate of release of ATP from 22S dynein was 0.01 s-1 per site at pH 7.0, 28 degrees C, assuming a molecular weight of 750 000 per site. The same method gave a rate of ATP synthesis by myosin subfragment 1 of 3.4 X 10(-4) s-1 at pH 7.0, 28 degrees C. The rate of ATP synthesis at the active site was estimated from the time dependence of medium phosphate-water oxygen exchange. Dynein was incubated with ADP and [18O] Pi, and the rate of loss of the labeled oxygen to water was monitored by 31P NMR. A partition coefficient of 0.31 was determined, which is equal to k-2/(k-2 + k3). Assuming k3 = 8 s-1 [Johnson, K.A. (1983) J. Biol. Chem. 258, 13825-13832], k-2 = 3.5 s-1. From the rates of ATP binding and hydrolysis measured previously (Johnson, 1983), the equilibrium constants for ATP binding and hydrolysis could be calculated: K1 = 5 X 10(7) M-1 and K2 = 14.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rate of ATP synthesis by dynein. 293 51

The mechanism of the sucrose synthetase reaction has been probed by the technique of positional isotope exchange. [beta-18O2, alpha beta-18O]UDP-Glc has been synthesized starting from oxygen-18-labeled phosphate and the combined activities of carbamate kinase, hexokinase, phosphoglucomutase, and uridine diphosphoglucose pyrophosphorylase. The oxygen-18 at the alpha beta-bridge position of the labeled UDP-Glc has been shown to cause a 0.014 ppm upfield chemical shift in the 31P NMR spectrum of both the alpha- and beta-phosphorus atoms in UDP-Glc relative to the unlabeled compound. The chemical shift induced by each of the beta-nonbridge oxygen-18 atoms was 0.030 ppm. Incubation of [beta-18O2, alpha beta-18O]UDP-Glc with sucrose synthetase in the presence and absence of 2,5-anhydromannitol did not result in any significant exchange of an oxygen-18 from the beta-nonbridge position to the anomeric oxygen of the glucose moiety. It can thus be concluded that either sucrose synthetase does not catalyze the cleavage of the scissile carbon-oxygen bond of UDP-Glc in the absence of fructose or, alternatively, the beta-phosphoryl group of the newly formed UDP is rotationally immobilized.
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PMID:Examination of the mechanism of sucrose synthetase by positional isotope exchange. 295 88

The rate and efficiency of energy transport were examined in a system containing isolated rabbit heart mitochondria, hexokinase, adenylate kinase and low concentrations of adenine nucleotides. Oxygen consumption by mitochondria and glucose-6-phosphate synthesis by hexokinase were registered. It was found that when adenylate kinase is active both in mitochondria and in the environmental solution, the rate and efficiency (glucose-6-phosphate/O ratio) of glucose-6-phosphate formation considerably increase. The effects of adenylate kinase activity are fully abolished by diadenosine pentaphosphate, an inhibitor of adenylate kinase.
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PMID:The effect of adenylate kinase activity on the rate and efficiency of energy transport from mitochondria to hexokinase. 298 36

The effect of adenylate kinase activity on the rate and efficiency of energy transport from mitochondria to hexokinase was studied in a system containing isolated rabbit heart mitochondria, hexokinase and adenylate kinase at low concentrations of adenine nucleotides. Oxygen consumption by mitochondria and glucose-6-phosphate synthesis by hexokinase were recorded. It was found that with adenylate kinase being active both in mitochondria and in the washing solution, the rate and efficiency of glucose-6-phosphate synthesis considerably increases. The effects of adenylate kinase activity are fully abolished by diadenosine pentaphosphate, an inhibitor of adenylate kinase. The experimental results based on the use of adenylate kinase demonstrate the possibility of increasing the rate and efficiency of energy transfer between two spatially uncoupled biochemical processes in vitro with the aid of an enzymatic system.
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PMID:[The role of adenylate kinase in the regulation of the rate and effectiveness of energy transfer from mitochondria to hexokinase in vitro]. 301 65

Glucose utilization in vivo and hexokinase activity and mitochondrial oxygen consumption in vitro were measured in a series of human brain tumors. Several relatively slow-growing tumors appeared to have depressed electron-transport activities coupled with a compensatory elevated glucose utilization. These data suggest that a decrease in oxidative metabolism and a corresponding increase in glycolysis are not necessarily correlated with malignancy in certain human brain tumors.
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PMID:Oxidative metabolism and glycolysis in benign brain tumors. 303 82

Hemoglobin affinity to oxygen, enzyme activity and metabolite concentration of carbohydrate metabolism were determined in erythrocytes of rats which were administered insulin solution. A valid decrease of the hemoglobin value P50 (pressure of hemoglobin half-saturation with oxygen), as well as a decrease of the enzyme activity of 2,3-diphosphoglycerate shunt and increase of the activity of regulatory glycolysis enzymes--hexokinase and pyruvate kinase in erythrocytes with multiple introduction of hormones to animals have been established. Such changes in rat erythrocytes were registered with the simultaneous effect of insulin and hypoxic hypoxia evoked by the "lift" of rats in the altitude chamber to the conditional altitude of 9000 m. It is found out that preliminary injection of insulin considerably increases survivability of rats under hypoxic hypoxia at great altitudes.
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PMID:[Oxygen-transport function and carbohydrate metabolism in rat erythrocytes during hypoxic hypoxia and treatment with insulin]. 307 Aug 87


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