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 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

Parenchymal cells from adult rat liver, isolated by a collagenase perfusion technique, have been maintained in primary culture and a detailed study on carbohydrate metabolism carried out over the initial 48-hour culture period. The glucose concentration of the medium exerts a major influence on glycogen accumulation by the cells. Insulin, particularly at high glucose concentrations, stimulates glycogen biosynthesis, whereas glucagon prevents glycogen accumulation. Dexamethasone was without effect on glycogen metabolism. Glucose appears to stimulate glycogen accumulation by activation of glycogen synthetase enzyme. However, there is a gradual loss of synthetase activity throughout the culture period. Similar decreases in activity were noted for pyruvate kinase, aldolase and hexokinase. Glucose, insulin and dexamethasone were unable to prevent these decreases in enzyme activity. Foetal bovine serum contains fructose and this hexose appears to be the factor in serum which is responsible for the activation of glycogen accumulation in the presence of physiological glucose concentrations. The lactic acid content of the serum may also stimulate glycogen accumulation. In general, there is a gradual loss of the pattern of carbohydrate metabolism typical of differentiated hepatocytes during the culture period.
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PMID:Effects of hormones and serum on glycogen metabolism in adult rat liver parenchymal cell primary cultures. 40 98

In the present study the effects of insulin, glucocorticoids and thyroid hormones on macrophage metabolism and function were investigated. The maximum activities of hexokinase, glucose-6-phosphate dehydrogenase, glutaminase and citrate synthase were determined in macrophages obtained from hormone-treated rats and those cultured for a period of 48 h in the presence of hormones. Macrophage phagocytosis was markedly inhibited by dexamethasone and thyroid hormones, remaining unchanged when insulin was added to the culture medium, however. The changes in the enzyme activities caused by hormone treatments of the rats were very similar to those found in culture. Insulin enhanced citrate synthase and hexokinase activities and diminished those of glutaminase and glucose-6-phosphate dehydrogenase. Dexamethasone had a similar effect except on glucose-6-phosphate dehydrogenase. The addition of thyroid hormones to the culture medium raised the activities of glutaminase and hexokinase and reduced that of citrate synthase. The results presented support the suggestion that the effects of insulin, glucocorticoids and thyroid hormones on immune and inflammatory responses could well be mediated through changes in macrophage metabolism.
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PMID:Effects of insulin, glucocorticoids and thyroid hormones on the activities of key enzymes of glycolysis, glutaminolysis, the pentose-phosphate pathway and the Krebs cycle in rat macrophages. 147 28

Dexamethasone decreases 2-D-deoxyglucose (2-dGlc) uptake and accumulation into rat peritoneal macrophages in vitro in a concentration- and time-dependent manner (Ki for 1 microM-dexamethasone after a 2 h exposure = 0.71 +/- 0.21 microM; Ki for 0.1 microM-dexamethasone after exposure for 4 h = 0.10 +/- 0.06 microM). The inhibition of 2-dGlc uptake is consistent with a decrease in the coupling between endofacial hexokinase activity and the sugar transporter. The evidence for this is: (1) the Km for zero-trans 2-dGlc uptake in quiescent macrophages was increased by dexamethasone, but there was no significant effect on the Vmax.; (2) dexamethasone increased the rate of exit of sugar from cells preloaded with 2-dGlc; (3). the free sugar accumulation within the cytosol of the cells above the external solution concentration was significantly decreased by dexamethasone. These effects of dexamethasone on 2-dGlc transport were antagonized by simultaneous exposure to the steroid RU 38486 (Ki = 0.04 +/- 0.01 microM; 4 h incubation). Although dexamethasone inhibited zero-trans uptake, the maximum rate of infinite-trans exchange uptake of 2-dGlc into cells preloaded with 3-O-methyl-D-glucose (40 mM) was unaltered by dexamethasone or RU 38486, indicating that the dexamethasone-dependent decrease in zero-trans uptake was not due to a change in the number of transporters in the plasma membrane. Dexamethasone also inhibited the phorbol myristate acetate-induced stimulation of hexose monophosphate shunt (HMPS) activity, and this was reversed by RU 38486. Cytochalasin B, the potent sugar-transport inhibitor, inhibited HMPS activity and 2-d[2,6-3H]Glc uptake equally, indicating a single site of action. By contrast, dexamethasone showed differential inhibition of HMPS activity and 2-d[2,6-3H]Glc uptake, suggesting that it not only acts by decreasing the coupling between hexokinase and sugar transport, but also at one or more additional points.
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PMID:Dexamethasone inhibits the hexose monophosphate shunt in activated rat peritoneal macrophages by reducing hexokinase-dependent sugar uptake. 188 24

Uptake of 3-O-methyl-D-glucoside (3-OMG) into thymocytes was studied to ascertain if it is modulated by endofacial hexokinase activity or by intracellular glucose. (1) The Vmax for net uptake of 3-OMG into rat thymocytes is increased by phorbol 12-myristate 13-acetate (PMA; 40 nM) or starvation for 4 h, and decreased by dexamethasone (1 microM). Starvation for 4 h abolishes the PMA-dependent increase in 3-OMG uptake; this effect is prevented by incubation in 2-deoxyglucose (2-dGlc; 1 mM). (2) Dexamethasone decreases 2-dGlc uptake, increases the rate of 2-dGlc exit and decreases accumulation of free 2-dGlc, consistent with decreased endofacial hexokinase activity. (3) 3-OMG uptake is decreased by preloading the cells with 2-dGlc or glucose, whereas preloading with 3-OMG (40 mM) increases uptake of 3-OMG. (4) The inhibitory effect of preloaded 2-dGlc or glucose on 3-OMG uptake is decreased by PMA. (5) Preloading cells with 3-OMG (40 mM) increases 2-dGlc influx in control and dexamethasone-treated cells, but not into PMA-treated cells. (6) The maximal rate of self-exchange of 3-OMG is similar in control, PMA- or dexamethasone-treated cells. These results are consistent with the following view: 3-OMG uptake is retarded by exchange with cytosolic glucose, or 2-dGlc. PMA, by increasing endofacial hexokinase activity, or starvation depletes glucose from the endofacial surface of the transporter, and hence increase 3-OMG uptake. Dexamethasone, by decreasing endofacial hexokinase activity, increases endofacial binding of glucose, and hence decreases 3-OMG uptake. Cytosolic 3-OMG competes with glucose for endofacial sites, and hence the maximal rates of exchange uptake of 3-OMG are similar in control, PMA- or dexamethasone-treated cells, as the activity of thymocyte glucose transporters is apparently unaltered.
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PMID:Effects of phorbol, dexamethasone and starvation on 3-O-methyl-D-glucose transport by rat thymocytes. Modulation of transport by altered trans effects. 230 67

The rate, key enzymes, and several metabolites of glycolysis in rat hepatoma (HTC) cells have been compared to those in rat hepatocytes. At 5 to 10 mM glucose, lactate release was greater in HTC cells. This could be explained in part by the absence of key gluconeogenic enzymes, by the substitution of glucokinase by hexokinase, and by an increase in phosphofructokinase 1 and pyruvate kinase activity. In addition, fructose 2,6-bisphosphate, the most potent stimulator of phosphofructokinase 1, was identified in HTC cells and shown to stimulate phosphofructokinase 1 partially purified from these cells. Dexamethasone increased the release of lactate in HTC cells. This glucocorticoid increased the concentration of fructose 2,6-bisphosphate and the Vmax of the enzyme that catalyzes its synthesis, phosphofructokinase 2. The data were consistent with an indirect effect at the gene level, mediated by glucocorticoid receptors. Dexamethasone had no effect on the other rate-limiting glycolytic enzymes. Several agents (adenosine, dibutyryl cyclic adenosine 3':5'-monophosphate, ethanol, antimycin) known to decrease fructose 2,6-bisphosphate in hepatocytes were without effect on this stimulator in HTC cells. DL-Glyceraldehyde inhibited glycolysis in HTC cells and eventually killed them. Although this substance decreased fructose 2,6-bisphosphate inhibition of glycolysis through an action at another level could not be ruled out.
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PMID:Fructose 2,6-bisphosphate and the control of glycolysis by glucocorticoids and by other agents in rat hepatoma cells. 316 12

1. The effect of dexamethasone (30 micrograms day-1 100 g-1 body wt.) on the metabolism of glucose and glutamine was studied in the small intestine of rats after 9 days of treatment. 2. Dexamethasone treatment resulted in negative nitrogen balance (P less than 0.001), and produced increases in the concentrations of plasma glucose (22%, P less than 0.05), alanine (32%, P less than 0.001) and insulin (127%, P less than 0.001), but a decrease in the plasma concentration of glutamine (20%, P less than 0.05). 3. Portal-drained visceral blood flow increased by approximately 22% (P less than 0.001) in dexamethasone-treated rats, and was accompanied by a decrease in the arterio-venous concentration difference of glucose (43%, P less than 0.001) and an increase in that of lactate (22%, P less than 0.05), glutamine (35%, P less than 0.01), glutamate (33%, P less than 0.01) and alanine (21%, P less than 0.05). 4. Enterocytes isolated from dexamethasone-treated rats showed decreased and increased rates of glucose and glutamine utilization, respectively. 5. The maximal activities of hexokinase, 6-phosphofructokinase, citrate synthase and oxoglutarate dehydrogenase were decreased (30-64%, P less than 0.001) in intestinal mucosal scrapings of dexamethasone-treated rats, whereas the activity of glutaminase was increased (35%, P less than 0.001). 6. It is concluded that glucocorticoid administration decreases the rate of glucose utilization but increases that of glutamine (both in vivo and in vitro) by the epithelial cells of the small intestine. This may be caused by changes in the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells.
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PMID:Effect of glucocorticoid treatment on glucose and glutamine metabolism by the small intestine of the rat. 340 28

The effect of adrenalectomy on specific activities of testicular hexokinase, 6-phosphofructokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and glycogen concentration have been studied. A general increase in specific activities of all enzymes was seen after adrenalectomy in rats of all ages studied. However, lactate dehydrogenase activity and glycogen concentration in pre-pubertal rats alone were depleted with no alteration in pubertal and adult animals. This was accompanied by increased prolactin titres, but gonadotrophins and testosterone were unaltered. Dexamethasone treatment returned all enzyme activities and hormonal profiles to normal.
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PMID:Effect of adrenalectomy and dexamethasone treatment on testicular enzymes involved in carbohydrate metabolism. 630 9

Dexamethasone inhibits sugar-dependent phorbol myristate acetate (PMA)-stimulated superoxide production and 2-deoxy-D-glucose (2-dGlc) transport in rat peritoneal macrophages (Rist, R.J., Jones, G.E. and Naftalin, R.J. (1991) Biochem. J. 278, 119-128; Rist, R.J. and Naftalin, R.J. (1991) Biochem J. 278, 129-135). Here it is shown that with glucose as a substrate, dexamethasone (0.1 microM) acts as a non-competitive inhibitor of PMA-induced superoxide production; decreasing the maximal rate of superoxide production (P < 0.001) without altering the Km. In contrast, with 2-dGlc as a substrate, dexamethasone shows competitive inhibition of PMA-stimulated superoxide production; increasing the Km of superoxide production, (P < 0.001) without altering the Vmax. The maximal rate of PMA-stimulated superoxide production with glucose as substrate is 10-12-fold in excess of the maximal rate with 2-dGlc as substrate. Diphenylene iodonium (DPI) is a non-competitive inhibitor of PMA-stimulated glucose-dependent superoxide production in macrophages, (Ki = 1-5 microM) and significantly reduces the activity of the PMA-induced hexose monophosphate shunt, (HMPS) (P < 0.01). However, DPI (1 microM) has no significant effect on the PMA-induced increase in 2-dGlc uptake, suggesting that the stimulus for HMPS activity and superoxide production is separate from the stimulus for hexose transport. A model is described which explains the observed differences in hexose transport and glucose- and 2-dGlc-dependent superoxide production in terms of the differences in metabolism of the two sugars. Accumulation of free 2-dGlc within the cytosol leads to saturation of hexokinase and hence, the effects of PMA and dexamethasone, which alter the coupling between hexokinase and the transporter, are only observed at low concentrations of 2-dGlc, where it is accumulated to sub-saturating levels. Since glucose is completely metabolized within the cell, PMA and dexamethasone increase and decrease, respectively, net uptake of sugar and superoxide production at all glucose concentrations.
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PMID:The relationship between sugar metabolism, transport and superoxide radical production in rat peritoneal macrophages. 838 27

GENBANK/dy examines the mechanisms of glucocorticoid-induced insulin resistance in rat soleus muscle. Glucocorticoid excess was induced by administration of dexamethasone to rats for 5 days. Dexamethasone decreased the sensitivity of 3-O-methylglucose transport, 2-deoxyglucose phosphorylation, glycogen synthesis and glucose oxidation to insulin. The total content of GLUT4 glucose transporters was not decreased by dexamethasone; however, the increase in these transporters in the plasma membrane in response to insulin (100 m-units/litre) was lessened. In contrast, the sensitivity of lactate formation to insulin was normal. The content of 2-deoxyglucose in the dexamethasone-treated muscle was decreased at 100 m-units/litre insulin, while the contents of glucose 6-phosphate and fructose 2,6-bisphosphate were normal at all concentrations of insulin studied. The maximal activity of hexokinase in the soleus muscle was not affected by dexamethasone; however, inhibition of this enzyme by glucose 6-phosphate was decreased. These results suggest the following. (1) Glucocorticoid excess causes insulin resistance in skeletal muscle by directly inhibiting the translocation of the GLUT4 glucose transporters to the plasma membrane in response to insulin; since the activity of hexokinase is not affected, the changes in the sensitivity of glucose phosphorylation to insulin seen under these conditions are secondary to those in glucose transport. (2) The sensitivity of glycogen synthesis and glucose oxidation to insulin is decreased, but that of glycolysis is not affected: a redistribution of glucose away from the pathway of glycogen synthesis and glucose oxidation could maintain a normal rate of lactate formation although the rate of glucose transport is decreased.
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PMID:Effects of glucocorticoid excess on the sensitivity of glucose transport and metabolism to insulin in rat skeletal muscle. 903 57


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