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)

Glyceraldehyde has been known to be an insulin secretagogue for more than 15 years. It has been (reasonably) assumed that glyceraldehyde enters the glycolytic pathway via its phosphorylation by ATP to form glyceraldehyde phosphate, a reaction catalyzed by the enzyme triokinase, and that subsequent metabolism is identical to that of glucose. glucose. However, up to now there have been no studies verifying the presence of triokinase in the pancreatic beta cell. We report here that (1) the activity of triokinase in pancreatic islets is very low, indicating that the activity is intrinsically low and/or the enzyme was rapidly inactivated during the preparation of tissue for assay; (2) the activity is much lower than glucose phosphorylating activity (hexokinase plus glucokinase) in islets, even though glyceraldehyde is a more efficient insulin secretagogue than glucose; (3) glyceraldehyde phosphate dehydrogenase from pancreatic islets can use glyceraldehyde as a substrate in place of glyceraldehyde phosphate (the Vmax of glyceraldehyde phosphate dehydrogenase from islets when glyceraldehyde is the substrate is 20-fold that of triokinase when glyceraldehyde is the substrate); and (4) the Km of glyceraldehyde phosphate dehydrogenase with respect to glyceraldehyde (4.8 mM) is similar to the concentration of glyceraldehyde that gives one-half maximal rates of insulin release from pancreatic islets, whereas the Km of triokinase with respect to glyceraldehyde is much lower (less than 50 microM). These data suggest that besides stimulating insulin release in islets via its entering metabolism by phosphorylation to glyceraldehyde phosphate in the triokinase reaction, glyceraldehyde could be phosphorylated by Pi in the glyceraldehyde phosphate dehydrogenase reaction to form glycerate 1-phosphate which is probably unmetabolizable in islets. The second reaction could drastically increase the NADH/NAD ratio in islets without providing substrates for hydrogen shuttles that reoxidize cytosolic NADH. Since an increased NAD(P)H/NAD(P) ratio is believed to be a key part of the signal for insulin release, such a mechanism would explain the potent insulinotropism of glyceraldehyde in short-term experiments. In addition, the formation of unmetabolizable acids may explain the toxic effects of long-term exposure of islets to glyceraldehyde and why glyceraldehyde causes the beta cell to become acidic, whereas glucose does not.
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PMID:Does glyceraldehyde enter pancreatic islet metabolism via both the triokinase and the glyceraldehyde phosphate dehydrogenase reactions? A study of these enzymes in islets. 253 42

In mice with streptozotocin-induced diabetes of 3 days' duration, the hexokinase/glucose-6-phosphatase (HK/G6Pase) ratio in the kidney was enhanced by 52% (mean +/- SEM: 0.40 +/- 0.04 vs. 0.26 +/- 0.03; p less than 0.02) compared to control mice as a result of a 25% increase of HK (16.68 +/- 0.93 vs. 13.31 +/- 1.04 nmol/min/mg protein; p = 0.05) and a 17% decrease of G6Pase (42.51 +/- 2.75 vs. 51.25 +/- 1.89; p less than 0.05). In contrast, as expected, the corresponding ratio (HK + glucokinase/G6Pase) was strikingly reduced in the liver. In 9-day diabetic mice, the kidney enzyme changes were much smaller; however, in a chronic disease such as diabetes, even minimal deviations from the normal may lead to significant metabolic changes with time. The enhanced HK/G6Pase ratio in the diabetic kidney suggests an increase in glucose utilization. This may contribute to the increased synthesis of glycogen, glycoproteins (including basement membrane) and RNA (via provision of ribose-phosphate) occurring in the diabetic kidney and supports the view that the kidney (as opposed to other tissues) shows an 'anabolic response' to diabetes.
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PMID:Increased hexokinase/glucose-6-phosphatase ratio in the diabetic kidney as index of glucose overutilization. 255 19

The activities of the hepatic glycolytic enzymes glucokinase (GKase) and hexokinase (HKase) in herbivorous Microtus arvalis were very low and the hepatic fructose-1,6-diphosphatase (FDPase) activities were almost the same as those in C57BL/6J mice. Glycosuria was observed in over 50% of voles fed on a low fibre, high concentrate diet. Voles with a high incidence of glycosuria for over 6 weeks became insulin deficient. In these diabetic voles, the hepatic GKase, HKase and FDPase activities decreased considerably as a result of diminished insulin secretion and fatty degeneration of the hepatic cells. It was considered that M. arvalis would be a useful animal model in which to study disorders of glucose utilization in herbivora.
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PMID:Hepatic enzyme activities and plasma insulin concentrations in diabetic herbivorous voles. 256 Oct 34

Bacillus sphaericus 2362 is pathogenic for mosquito larvae and is being considered for large-scale production as a larvicide. The inability of the bacteria to metabolize carbohydrates requires that they be grown on proteinaceous media. This bacterium was found to be unable to transport glucose or sucrose into the cell, and it lacked glucokinase and hexokinase activity. In addition, it lacked phosphoglucose isomerase, phosphofructokinase, and glucose 6-phosphate dehydrogenase, which are early enzymes of the Embden-Myerhof-Parnas and hexose monophosphate pathways. The presence of other enzymes in these pathways was indicated by assay, by the metabolism of glycerol to acetate, and by growth on acetate and gluconate as sole carbon sources. Critical enzymes of the Entner-Doudoroff pathway were also shown to be absent.
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PMID:Carbohydrate metabolism in the mosquito pathogen Bacillus sphaericus 2362. 256 98

In rat pancreatic islets the effects of cholecystokinin octapeptide (CCK-8) on pentose phosphate shunt (PPS) activity, glucokinase and hexokinase activity, and NADPH, NADP+, NADH, and NAD+ were studied. By elevating the glucose concentration from 3.0 to 8.3 and 16.7 mM the oxidation of [1-14C]- and [6-14C]glucose and the calculated PPS activity were increased in a concentration-dependent manner; 10 nM CCK-8 enhanced selectively the effect on [1-14C]glucose oxidation thereby increasing the PPS activity but only at an intermediate glucose concentration (8.3 mM). CCK-8 had no effect on glucokinase or hexokinase activity and CCK-8 did not influence glucose utilization. By elevating the glucose concentration, total NADPH and NADH were increased and total NADP+ and NAD+ were decreased. CCK-8 (10 nM) increased selectively NADPH and decreased NADP+ but did not change NADH or NAD+; the effect of CCK-8 on NADPH and NADH was only observed in the presence of an intermediate stimulatory glucose concentration (8.3 mM) but not at either a substimulatory glucose concentration or a maximally stimulatory glucose concentration for insulin release (3.0 or 16.7 mM). The data indicate first that CCK-8 does not act on glucose phosphorylation or glucose utilization and second that CCK-8 increases PPS activity and NADPH levels in rat pancreatic islets. Since the concentrations of glucose necessary for these CCK-8 effects are in the range of 8.3 mM and parallel with those necessary for insulin release as shown in earlier observations, glucose oxidation via pentose phosphate shunt and NADPH are suggested to be related to the CCK-8-modulated insulin release.
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PMID:Effect of CCK-8 on pentose phosphate shunt activity, pyridine nucleotides, and glucokinase of rat islets. 264 44

Aconitan A did not affect plasma insulin levels in normal, glucose-loaded and alloxan-induced hyperglycemic mice and gave no influence on insulin binding to isolated adipocytes. Aconitan A exerted no effect on the activities of hepatic hexokinase, glucokinase, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase, whereas it significantly increased hepatic phosphofructokinase activity. Although the activity of hepatic glycogen synthetase showed a tendency to increase, the activity of liver phosphorylase and glycogen content were unchanged by aconitan A. Aconitan A did not change the total cholesterol and triglyceride contents of plasma and liver.
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PMID:Mechanisms of hypoglycemic activity of aconitan A, a glycan from Aconitum carmichaeli roots. 266 53

The early stages of insulin-dependent diabetes mellitus are characterized by a selective inability to secrete insulin in response to glucose, coupled to a better response to nonnutrient secretagogues. The deficient glucose response may be a result of the autoimmune process directed toward the beta-cells. Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells. In the present study we characterized the sensitivity of beta-cells to different secretagogues after human recombinant IL-1 beta (rIL-1 beta) exposure. Furthermore, experiments were performed to clarify the biochemical mechanisms behind the defective insulin response observed in these islets. Rat pancreatic islets were isolated and kept in tissue culture (medium RPMI-1640 plus 10% calf serum) for 5 days. The islets were subsequently exposed to 60 pM human recombinant IL-1 beta during 48 h in the same culture conditions as above and examined immediately after IL-1 exposure. The rIL-1 beta-treated islets showed a marked reduction of glucose-stimulated insulin release. Stimulation with arginine plus different glucose concentrations, and leucine plus glutamine partially counteracted the rIL-1 beta-induced reduction of insulin release. The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets. Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase. The oxidation of D-[6-14C]glucose and L-[U-14C]leucine were decreased by 50% in IL-1-treated islets. Furthermore, there was a significant decrease in the ratios of [2-14C]pyruvate oxidation/[1-14C]pyruvate decarboxylation and L-[U-14C]leucine oxidation/L-[1-14C]leucine decarboxylation, indicating that IL-1 decreases the proportion of generated acetyl-coenzyme-A residues undergoing oxidation. However, in the presence of IL-1 there was a significant increase in L-[U-14C]glutamate oxidation. These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism. This mitochondrial dysfunction seems to reflect an impairment in proximal steps of the Krebs cycle. It is conceivable that the IL-1-induced suppression and shift in islet metabolism can be an explanation for the beta-cell insensitivity to glucose observed in the early phases of human and experimental insulin-dependent diabetes mellitus.
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PMID:Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta. 266 6

Ganoderan B increased the plasma insulin level in normal and glucose-loaded mice but elicited no effect on insulin binding to isolated adipocytes. Administration of ganoderan B elicited significant increases of the activities of hepatic glucokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase, decreased the hepatic glucose-6-phosphate and glycogen synthetase activities and did not affect the activities of hexokinase and glycogen phosphorylase. Ganoderan B reduced the glycogen content in the liver but had no influence on total cholesterol and triglyceride levels in the plasma and liver.
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PMID:Mechanisms of hypoglycemic activity of ganoderan B: a glycan of Ganoderma lucidum fruit bodies. 268

Glucokinase, hexokinase, fructose 1,6-bisphosphatase and phosphoenolpyruvate carboxykinase specific activities were monitored in liver cytosol from rats that had been made cancerous with 1,2-dimethylhydrazine and then treated with hydrazine sulfate. The presence of intestinal cancer, specifically, was confirmed by laparotomy and by histological analysis. Sustained changes in hexokinase and glucokinase specific activities were first evident during the latter weeks that the carcinogen was being administered. Upon subsequent treatment with hydrazine sulfate, glucokinase activity further decreased, and liver cytosolic phosphoenolpyruvate carboxykinase activity increased. Liver cytosolic hexokinase and fructose 1,6-bisphosphatase specific activities were not appreciably affected by the hydrazine sulfate treatment. These results indicate that hydrazine sulfate may influence carbohydrate metabolism at the level of selected liver enzymes not only with respect to gluconeogenesis, but also in terms of glucose uptake.
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PMID:Effect of hydrazine sulfate on glucose-regulating enzymes in the normal and cancerous rat. 270 33

Porcine hepatic glucokinase (ATP: D-hexose 6-phosphotransferase EC 2.7.1.1) has been purified by a modification of the procedure for its purification from rats. However, difficulties were encountered with endogenous proteases and the reliability of a source for porcine livers. The molecular weight has been determined to be 60,400 +/- 1,400 by sodium dodecyl sulfate, polyacrylamide gel electrophoresis. The enzyme has been characterized kinetically. The parameter values, S0.5 (glucose) and Hill coefficient (nH) are 2.4 mM and 1.9 respectively under sulfhydryl-reducing conditions. The enzyme undergoes the two sulfhydryl-related decays of its activity previously observed in the enzyme isolated from rat (Tippett PS, Neet KE: Arch Biochem Biophys 222:285-298, 1983). The enzyme is inhibited by palmitoyl-CoA, Ki (apparent) = 1.0 microM, nH = 1.8; this concentration of inhibitor is significantly below its critical micelle concentration. Physically and kinetically glucokinase isolated from pig is similar to the enzyme isolated from rat. The porcine system provides a second source for isolation and further characterization of this important and unusual enzyme.
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PMID:The regulatory kinetic properties of porcine hepatic glucokinase. 277 Jul 13


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