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 administration of dexamethasone to rats markedly diminished the initial rate and maximal extent of substrate-dependent calcium uptake in subsequently isolated liver mitochondria, and enhanced the release of calcium. The apparent Km for calcium transport was not altered by dexamethasone treatment and it ranged from 50 to 80 muM when an EDTA/Ca buffer system was used in the presence of magnesium, and 20 muM when an NTA/Ca buffer system without magnesium was employed. In contrast, when ATP was employed as the energy source, there was no significant difference in initial rate, Km, or the extent of calcium accumulation between mitochondria from control and dexamethasone-treated animals. Although mitochondria from dexamethasone-treated animal showed 15% less cytochrome c oxidase activity/mg of protein, overall respiratory capacity and ATP production from ADP were the same as in control mitochondria. However, mitochondria from dexamethasone-treated animals translocated ATP from inside to outside faster than those from control animals. When the ATP in the medium was depleted by glucose and hexokinase, both types of mitochondria retained essentially all the preloaded calcium until total ATP reached a critical level (7 approximately 5 mumol of ATP/mg of protein). When ATP content fell below this critical level, mitochondria released all the calcium quickly. Dexamethasone treatment increased the susceptibility of mitochondria to the depletion of ATP. These data indicate that the dexamethasone-induced decrease in maximal calcium transport and in calcium retention carrier system per se, but o an altered ability of the mitochondria to regulate intramitochondrial ATP content.
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PMID:Adrenal glucocorticoids, adenine nucleotide translocation, and mitochondrial calcium accumulation. 19 Feb 24

Keeping constant cellular magnesium an A 23 187 mediated moderate calcium loading of human red cells causes isoosmotic cell shrinkage, potassium efflux, slight decrease of cellular pH, ATP depletion connected with an increase of AMP, ADP and Pi and enhanced lactic acid formation. The calcium loading and accompanying effects can be abolished by EGTA or by extracellular magnesium, the latter kept more than two orders of magnitude above that of calcium which was 30 micrometer. Inhibition of the (Mg2+ + Ca2+)-dependent ATPase by ruthenium red or lanthanum decreases the calcium stimulated lactic acid formation after a lag phase. However, the ATP depletion proceeds faster and is much more pronounced under these conditions. (Mg+2 + Na+ +K+)-dependent ATPase, hexokinase, phosphofructokinase and cell shrinkage are ruled out, too, as mediators of the ATP depletion. This suggests that an unknown ATP consuming reaction, apparently not being related to the calcium pump, causes the calcium induced ATP depletion.
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PMID:Relations between ion shifting, ATP depletion and lactic acid formation in human red cells during moderate calcium loading using the ionophore A 23187. 33 40

1. A dose-dependent activation of phosphorylase and consumption of ATP was observed in isolated hepatocytes incubated in the presence of fructose; histone kinase and phosphorylase kinase activities were unchanged at doses of this sugar that were fully effective on phosphorylase. The activation of phosphorylase by fructose was also observed in cells incubated in a Ca2+-free medium as well as in the livers of rats in vivo. 2. In a liver high-speed supernatant, fructose, tagatose and sorbose stimulated the activity of phosphorylase kinase; this effect was dependent on the presence of K+ ions, which are required for the activity of fructokinase; it was accompanied by the transformation of ATP into ADP. In the presence of hexokinase, glucose also stimulated phosphorylase kinase, both in an Na+ or a K+ medium. 3. The activities of partially purified muscle or liver phosphorylase kinase were unchanged in the presence of fructose. 4. Some properties of liver phosphorylase kinase are described, including a high molecular weight and an inhibition at ATP/Mg ratios above 0.5, as well as an effect of ATP concentration on the hysteretic behaviour of this enzyme. 5. The effect of fructose on the activation of phosphorylase is discussed in relation to the comsumption of ATP.
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PMID:Mechanism of activation of glycogen phosphorylase by fructose in the liver. Stimulation of phosphorylase kinase related to the consumption of adenosine triphosphate. 43 71

To learn whether a single dialysis can acutely improve the intravenous glucose tolerance (i.v.GTT) of chronically dialyzed patients, a standard i.v.GTT was performed on 10 nonobese uremic subjects on maintenance hemodialysis for 27 +/- 9 (mean +/- SEM) mo, and on a control group of 13 normal subjects. The uremic patients were tested first 0.2-17 (range) hr, and then 65-109 hr, from last dialysis. In the uremic sera, plasma glucose was analyzed by 4 methods; 2 reducing (neocopurine and ferricyanide) and 2 enzymatic (hexokinase and glucose oxidase). The reducing methods markedly overestimated plasma glucose concentration because of the presence of nonglucose reducing substances (notably, creatinine). This inteference was significantly cut down by dialysis. A single dialysis, on the other hand, failed to improve the glucose fractional decay rate (KG) computed from the glucose oxidase data (1.69 +/- 0.2%/min before and 1.35 +/- 0.1 after dialysis, versus 1.47 +/- 0.1 of the normal subjects). The same conclusion was derived from the data measured by the other 3 methods of glucose assay. Fasting plasma insulin concentrations were, on average, above normal (5.5 +/- 0.6 muU/ml) both before (12.3 +/- 2.7, p less than 0.05) and after (17.2 +/- 3.5, p less than 0.01) a single dialysis. Likewise, the area under the glucose-induced plasma insulin curve was significantly greater than normal (1.46 +/- 0.21 mU/ml . min) both before (2.26 +/- 0.34, p less than 0.05), and after (2.86 +/- 0.43, p less than 0.01) dialysis. A single dialysis had little effect on either basal or glucose-stimulated insulin release, and no significant difference in the insulinogenic index (insulin area/glucose area) was found between the control and the uremic group in either test. Insulin response was not correlated with KG, whereas it was significantly associated with higher triglyceride levels. Creatinine, urea or methylguanidine did not appear to have any influence on KG, but lower serum potassium levels were significantly associated with poorer i.v.GTT's. Plasma calcium bore a reciprocal relation to the insulinogenic index. Chronically dialyzed subjects show some degree of tissue insulin resistance, which a single dialysis fails to correct. Electrolyte disturbances may play a role in this metabolic derangement.
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PMID:The response to intravenous glucose of patients on maintenance hemodialysis: effects of dialysis. 76 47

(1) Ca2+ efflux from rabbit skeletal muscle sarcoplasmic reticulum vesicles pre-loaded with 45Ca2+ was studied in the presence and in the absence of external Ca2+. (2) In the absence of Ca2+ in the assay media, ADP activates the Ca2+ efflux. The increment of Ca2+ efflux requires Pi, is coupled to ATP synthesis, and is inhibited by external Ca2+ (Ki 0.1-0.2 muM). (3) When Ca2+ is added to the assay media, ADP alone activates the Ca2+ efflux, but this is coupled to a Ca2+ influx of the same magnitude. It is therefore an exchange of internal for external Ca2+ in a 1:1 ratio. (4) The ADP-activated Ca2+ exchange requires external Ca2+ with an apparent Km of 0.1-0.2 muM, does not require the addition of Pi or Mg2+, although 3-10 mM MgCl2 activates it. It is not inhibited by the removal of contaminating ATP with hexokinase plus glucose. (5) It seems likely that Ca2+ can be translocated across sarcoplasmic reticulum membrane without the formation of a phosphorylated intermediate.
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PMID:ADP-activated calcium ion exchange in sarcoplasmic reticulum vesicles. 81 33

1. The effects of protein concentration and ionic strength on the adsorption of the individual glycolytic enzymes to F-actin and F-actin--trypomyosin--troponin have been studied. 2. Appreciable association was demonstrated under conditions of physiological ionic strength and high protein concentration, and tropomyosin--troponin established as an important and generalized component of these interactions. 3. Phosphofructokinase, aldolase, pyruvate kinase, lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate isomerase were strongly bound under these conditions, while triosephosphate isomerase, phosphoglycerate kinase, phosphoglycerate mutase, enolase and hexokinase displayed less adsorption to the structural proteins. 4. The influence of a number of parameters on the adsorption phenomena was examined. Ca2+ and fructose 1,6-diphosphate increased the adsorption of aldolase, lactate dehydrogenase and pyruvate kinase, while decreasing the adsorption of the enzymes of the constant-proportion group. 5. Of the other major enzymic components of skeletal muscle, creatine kinase, adenylate kinase and malate dehydrogenase showed no adsorption to F-actin--tropomyosin--troponin under the experimental conditions. Some adsorption was evident, however, in the case of aspartate aminotransferase, (NADP) isocitrate dehydrogenase and alpha-glycerolphosphate dehydrogenase. 6. These results have been discussed in relation to their functional significance and the roles of enzyme compartmentation in the cell.
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PMID:On the association of glycolytic enzymes with structural proteins of skeletal muscle. 111 88

Ca2+ inhibitory effect on hexokinase (HK) and pyruvatkinase activities is studied. Kinetic analysis of the inhibition reaction is carried out to determine the inhibition type. Non-competitive inhibition with respect to reaction activator, Mg2+, is found for HK and PK. On the basis of graph analysis data for both reactions the values of the activatory constant (KA) and the inhibitory constant (Ki) are calculated. The experimental results are discussed with respect to possible regulatory effect of Ca2+ on glycolysis cycle.
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PMID:[Identification of the inhibition type of hexokinase and pyruvate kinase activity by Ca2+]. 120 96

In the presence of hexokinase, vesicles derived from the sarcoplasmic reticulum of skeletal muscle are able to accumulate Ca2+ in a medium containing ADP and glucose 6-phosphate. No significant Ca2+ uptake is observed if one of these components is omitted from the assay medium. Due to its high affinity for ATP, the Ca(2+)-ATPase can use the very low concentrations of ATP formed from glucose 6-phosphate and ADP to form a Ca2+ gradient. This finding indicates that glucose 6-phosphate and hexokinase can be used as an ATP-regenerating system. The Ca2+ uptake supported by glucose 6-phosphate and ADP is inhibited by glucose and D-xylose. Half-maximal inhibition is observed in the presence of 0.4 mM glucose and 100 mM D-xylose. The transport ratio (Ca2+ transported:substrate utilized) is the same for glucose 6-phosphate and ATP. The Ca2+ gradient formed when glucose 6-phosphate and ADP are the substrates can be used to synthesize ATP from ADP and Pi. The concentration of ATP formed after reversal of the Ca2+ pump is much higher than that expected from direct equilibration of the reaction between glucose 6-phosphate and ADP.
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PMID:Glucose 6-phosphate and hexokinase can be used as an ATP-regenerating system by the Ca(2+)-ATPase of sarcoplasmic reticulum. 130

A smooth muscle plasma membrane vesicular fraction (PMV) purified for the (Ca2+/Mg2+)-ATPase has endogenous glycolytic enzyme activity. In the presence of glycolytic substrate (fructose 1,6-diphosphate) and cofactors, PMV produced ATP and lactate and supported calcium uptake. The endogenous glycolytic cascade supports calcium uptake independent of bath [ATP]. A 10-fold dilution of PMV, with the resultant 10-fold dilution of glycolytically produced bath [ATP] did not change glycolytically fueled calcium uptake (nanomoles per milligram protein). Furthermore, the calcium uptake fueled by the endogenous glycolytic cascade persisted in the presence of a hexokinase-based ATP trap which eliminated calcium uptake fueled by exogenously added ATP. Thus, it appears that the endogenous glycolytic cascade fuels calcium uptake in PMV via a membrane-associated pool of ATP and not via an exchange of ATP with the bulk solution. To determine whether ATP produced endogenously was utilized preferentially by the calcium pump, the ATP production rates of the endogenous creatine kinase and pyruvate kinase were matched to that of glycolysis and the calcium uptake fueled by the endogenous sources was compared with that fueled by exogenous ATP added at the same rate. The rate of calcium uptake fueled by endogenous sources of ATP was approximately twice that supported by exogenously added ATP, indicating that the calcium pump preferentially utilizes ATP produced by membrane-bound enzymes.
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PMID:Comparison of endogenous and exogenous sources of ATP in fueling Ca2+ uptake in smooth muscle plasma membrane vesicles. 131 Oct 20

During steady-state, the Pi released in the medium is derived from glucose-6-phosphate which continuously regenerates the ATP hydrolyzed. A membrane potential (delta psi) can be built up in submitochondrial particles using glucose-6-phosphate and hexokinase as an ATP-regenerating system. The energy derived from the membrane potential thus formed, can be used to promote the energy-dependent transhydrogenation from NADH to NADP+ and the uphill electron transfer from succinate to NAD+. In spite of the large differences in the energies of hydrolysis of ATP (delta G degrees = -7.0 to -9.0 kcal/mol) and of glucose-6-phosphate (delta G degrees = -2.5 kcal/mol), the same ratio between Pi production and either NADPH or NADH formation were measured regardless of whether millimolar concentrations of ATP or a mixture of ADP, glucose-6-phosphate and hexokinase were used. Rat liver mitochondria were able to accumulate Ca2+ when incubated in a medium containing hexokinase, ADP and glucose-6-phosphate. The different reaction measured with the use of glucose-6-phosphate and hexokinase were inhibited by glucose concentrations varying from 0.2 to 2 mM. Glucose shifts the equilibrium of the reaction towards glucose-6-phosphate formation thus leading to a decrease of the ATP concentration in the medium.
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PMID:Reversal of oxidative phosphorylation in submitochondrial particles using glucose 6-phosphate and hexokinase as an ATP regenerating system. 149 30


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