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)

Addition of 0.4-25 microM extracellular ATP results in transient, dose-dependent increases in cytosolic free calcium measured in Ehrlich ascites tumor cells. In cells incubated with 1 mM extracellular Ca2+, ATP induces a triphasic Ca2+ transient: an initial rapid increase (2-3 s), a second, slower phase of increase (60-90 s), and, finally, a gradual return to near resting [Ca2+]i (4-5 min). Several findings demonstrate that the initial, rapid phase of Ca2+ transient results from a mobilization of Ca2+ from a non-mitochondrial intracellular store, while the second, slow phase of increase is produced by enhanced influx of Ca2+ across the plasma membrane. Successive additions of extracellular ATP can elicit repetitive Ca2+ transients if the initially added ATP is removed either through the action of native ecto-ATPase activity or exogenous hexokinase. Other adenine nucleotides, including non-hydrolyzable ATP analogs, neither alter cytosolic [Ca2+] nor antagonize the ATP-induced effects. Conversely, other nucleotide triphosphates (ITP, UTP, and GTP) induce Ca2+ transients which are identical to those produced by ATP. A variety of experimental results indicate that these actions of ATP and other nucleotide triphosphates are not due to a generalized increase in plasma membrane permeability. The results suggest that, in these transformed cells, ATP may act in a manner similar to other Ca2+ mobilizing hormones and growth factors.
J Biol Chem 1985 Sep 05
PMID:Intracellular Ca2+ mobilization activated by extracellular ATP in Ehrlich ascites tumor cells. 403 Jul 63

5-Thioglucose (5-TG) had a marked effect on the energy metabolism of Schistosoma mansoni in vitro: the conversion of external glucose into lactate by intact worms was severely inhibited. This inhibition of glycolysis was instantaneous, independent of the oxygen concentration and competitive with respect to glucose. Degradation of 0.5 mM external (14C-labelled) glucose was inhibited for 80% in the presence of 20 mM 5-TG. On the other hand the degradation of endogeneous glycogen to lactate was uninhibited. This shows that the inhibition of glucose breakdown occurred at the entrance of glucose into the cell and/or at the hexokinase reaction. It was demonstrated that 5-TG inhibited both the uptake of glucose and the activity of hexokinase. However, it was concluded that in the intact worm 5-TG blocked glycolysis by its competitive inhibition of hexokinase. In intact S. mansoni worms hexokinase is probably the rate-limiting enzyme of glycolysis. Krebs-cycle activity and lactate production do not occur at a fixed ratio: at lower rates of pyruvate formation Krebs-cycle activity was favoured.
Biochem Pharmacol 1985 Sep 15
PMID:The effect of 5-thioglucose on the energy metabolism of Schistosoma mansoni in vitro. 403 43

The metabolic properties of mitochondria from rat cerebral cortex and olfactory bulb were investigated. The pyruvate-supported oxygen uptake rates by olfactory bulb mitochondria were significantly lower than those by cerebrocortical mitochondria. This is consistent with the differences in pyruvate dehydrogenase complex activities between these mitochondrial preparations. Pyruvate dehydrogenase kinase, NAD-linked isocitrate dehydrogenase, and hexokinase activities in olfactory bulb mitochondria were significantly lower than those in cerebrocortical mitochondria. However, NADP-linked isocitrate dehydrogenase, and NAD-linked and NADP-linked glutamate dehydrogenase activities in olfactory bulb mitochondria were significantly higher than those in cerebrocortical mitochondria. The differences between these two mitochondrial preparations in terms of the activities of these energy-metabolizing enzymes reflect the differences detected in the homogenates of these regions.
Brain Res 1985 Sep 16
PMID:Differences in some of the metabolic properties of mitochondria isolated from cerebral cortex and olfactory bulb of the rat. 404 57

A 14-month-old child who had a haemolytic episode when he was 5 years old, and with psychomotor retardation, was found to have decreased red cell hexokinase activity. The mutant enzyme was characterized by an increased affinity for glucose associated with an increased inhibition constant for glucose-1,6-diphosphate. Affinity for Mg ATP2-, heat stability and pH-optimum were normal. The isozymic pattern of the red cell enzyme was normal but all the molecular forms were present in reduced amounts. The kinetics of decay of hexokinase during cell ageing was also normal. Glucose consumption of the hexokinase deficient cells was 60-65% of the controls while the amount metabolized through the hexose monophosphate shunt was unchanged. Red cell 2,3-diphosphoglycerate and glucose-6-phosphate levels were normal in the proband but reduced in the erythrocytes of his parents, who were heterozygous for the defect but had normal haematological data. Comparison with the 13 previously reported cases of hexokinase deficiency confirms the broad phenotypic variability that characterizes this disorder.
Br J Haematol 1985 Sep
PMID:Human erythrocyte hexokinase deficiency: a new variant with abnormal kinetic properties. 405 30

The age dependent behaviour of 11, mainly glycolytic, red blood cell enzymes in 26 patients with various haematological disorders has been investigated after separation of red blood cells by discontinuous density gradient centrifugation. The frequency of enzyme deficiencies in the old cells of these patients was significantly increased in comparison with the unseparated cells, 29 and 13 deficiencies, respectively. Particularly hexokinase activity, although normal or even increased in unseparated cells, was found deficient in old cells in seven cases. In addition, an increased number of phosphofructokinase deficiencies was observed in the patients' old cells (eight cases) as compared to the unseparated cells (three cases). However, the red blood cells of the majority of these patients were found to contain increased enzyme activities, irrespective of cell age. Enzyme activities in the youngest cell population did not correlate with the reticulocyte count. Cases of high pyruvate kinase and hexokinase activities were studied for kinetical, electrophoretical and immunological properties of the respective enzymes, but no abnormalities could be demonstrated, indicating an increased synthesis of these enzymes.
Br J Haematol 1985 Sep
PMID:Age dependent behaviour of red cell glycolytic enzymes in haematological disorders. 405 31

Lactose biosynthesis and relevant enzymatic activity in rabbit mamma ry tissue during various stages of pregnancy and lactation are investigated by using a tissue-slice incubation method in order to understand the temporal relationships. Ovulation was induced in 27 New Zealand white rabbits and they were bred by artificial insemination. Sacrifice occurred on days 15, 24, and 29 of pregnancy, and day 2, 5, 8, 15, and 22 post partum. Nucleic acids were extracted and concentratons of DNA determined spectrophotometrically at 600 nm with diphenylamine reagent and RNA determined with orcinal reagent. The tissue incubations were made with (U-14C) glucose. (14C) lactose was then separated by paper chromatography from unchanged radioactive glucose. Enzyme analysis including determining the activities of phosphoglucomutase, UDP-glucose pyrophosphorylase, and UDP-glucose 4-epimerase. Lactose synthase was determined, as well as, hexokinase. A biphasic adaptation in the rate of lactose synthesis and in the RNA concentration was noted during lactogenesis. The 1st increase in the rate of lactose biosynthes is occurred between days 15 and 24 of pregnancy. A 2nd substantial increase was noted immediately post partum. The overall rate of lactose biosynthesis increased 12-fold from day 24 of pregnancy to day 15 of lactation post partum, and then decreased from 15 to 22 days post partum. The RNA concentration/g wet weight of tissue and the ratio of RNA/DNA closely represented the biphasic ability of the mammary-tissue slice to synthesize lactose. Increases in the activities of UDP-glucose 4-epimerase and lactose synthase were most closely correlated with increases in the rate of lactose biosynthesis. UDP-glucose pyrophosphor ylase activity was unrelated with the ability to synthesize lactose, and hexokinase and phosphoglucomutase activities were variable during pregnancy and lactation. Lactose synthase activity was present by day 15 of pregnancy, but the ability to synthesize lactose was undetected until day 24 of pregnancy.
Biochem J 1974 Sep
PMID:Metabolic adaptations during lactogenesis. Lactose synthesis in rabbit mammary tissue during pregnancy and lactation. 421 77

1. Adipose tissues from rats fed a balanced diet were incubated in the presence of glucose (20mm) with the following additions: insulin, anti-insulin serum, insulin+acetate, insulin+pyruvate, insulin+lactate, insulin+phenazine methosulphate, insulin+oleate+albumin, insulin+adrenaline+albumin, insulin+6-N-2'-O-dibutyryl 3':5'-cyclic AMP+albumin. 2. Measurements were made of the whole tissue concentrations of adenine nucleotides, hexose phosphates, triose phosphates, glycerol 1-phosphate, 3 phosphoglycerate, 6-phosphogluconate, long-chain fatty acyl-CoA, acid-soluble CoA, citrate, isocitrate, malate and 2-oxoglutarate, and of the release into the incubation medium of lactate, pyruvate and glycerol after 1h of incubation. 3. Fluxes of [(14)C]glucose carbon through the major pathways of glucose metabolism were calculated from the yields of (14)C in various products after 2h of incubation. Fluxes of [(14)C]acetate, [(14)C]pyruvate or [(14)C]lactate carbon in the presence of glucose were also determined. 4. Measurements were also made of the whole-tissue concentrations of metabolites in tissues taken directly from Nembutal-anaesthetized rats. 5. Whole tissue mass-action ratios for phosphofructokinase, phosphoglucose isomerase and the combined (aldolasextriose phosphate isomerase) reaction were similar in vivo and in vitro. The reactants of phosphofructokinase appeared to be far from mass-action equilibrium. In vitro, the reactants of hexokinase also appeared to be far from mass-action equilibrium. 6. Correlation of observed changes in glycolytic flux with changes in fructose 6-phosphate concentration suggested that phosphofructokinase may show regulatory behaviour. The enzyme appeared to be activated in the presence of oleate or adrenaline and to be inhibited in the presence of lactate or pyruvate. 7. Evidence is presented that the reactants of lactate dehydrogenase and glycerol 1-phosphate dehydrogenase may be near to mass-action equilibrium in the cytoplasm. 8. No satisfactory correlations could be drawn between the whole-tissue concentrations of long-chain fatty acyl-CoA, citrate and glycerol 1-phosphate and the observed rates of triglyceride and fatty acid synthesis. Under the conditions employed, the concentration of glycerol 1-phosphate appeared to depend mainly on the cytoplasmic [NAD(+)]/[NADH] ratios. 9. Calculated hexose monophosphate pathway flux rates roughly correlated with fatty acid synthesis rates and with whole tissue [6-phosphogluconate]/[glucose 6-phosphate] ratios. The relative rates of production of NADPH for fatty acid synthesis by the hexose monophosphate pathway and by the ;malic enzyme' are discussed. It is suggested that all NADH produced in the cytoplasm may be used in that compartment for reductive synthesis of fatty acids, lactate or glycerol 1-phosphate.
Biochem J 1970 Sep
PMID:The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. 439 81

(1) A ;cycling' method involving citrate synthase (EC 4.1.3.7) and malate dehydrogenase (EC 1.1.1.37) was modified by the inclusion of succinyl-CoA synthetase (EC 6.2.1.5) and hexokinase (EC 2.7.1.1) to permit the determination of very small amounts of succinyl-CoA in addition to CoA and acetyl-CoA. (2) Application of this technique to blowfly (Phormia regina) flight-muscle extracts reveals no change in acetyl-CoA concentration, a slight fall in CoA concentration and a rise in succinyl-CoA concentration during flight. (3) Extraction of isolated mitochondria during controlled (state 4) pyruvate oxidation reveals essentially only acetyl-CoA. Activation of respiration by ADP (state 3) or uncoupling agents leads to a fall in acetyl-CoA and a rise in CoA and succinyl-CoA content. (4) The presence of glycerol phosphate in addition to pyruvate results in a lower acetyl-CoA content in state 4. (5) It is contended that these results are consistent with a primary control of one of the reactions of the tricarboxylate cycle, rather than of pyruvate dehydrogenase, during the state 4 oxidation of pyruvate by isolated mitochondria, and that the modulation of citrate synthase activity by the ratio of acetyl-CoA/succinyl-CoA is unimportant under these conditions.
Biochem J 1974 Sep
PMID:The control of tricarboxylate-cycle of oxidations in blowfly flight muscle. The steady-state concentrations of coenzyme A, acetyl-coenzyme A and succinyl-coenzyme A in flight muscle and isolated mitochondria. 446 39

1. The submitochondrial localization of hexokinase activity in preparations of mitochondria from the small intestine of the guinea pig was studied by conventional methods. 2. Hexokinase activity in this tissue was predominantly associated with the outer mitochondrial membrane. 3. The inactivation of mitochondrial enzymes by trypsin in iso-osmotic and hypo-osmotic conditions was also used to determine the submitochondrial localization of hexokinase activity. 4. Hexokinase activity was found to be on the outside of the outer mitochondrial membrane. 5. It was shown that both type I and type II hexokinase activities are bound to the outside of the outer mitochondrial membrane. The types are present in the same ratio as that in which they occur in the cytosol of the cell. 6. Mitochondrial hexokinase from the small intestine did not show the latency phenomenon demonstrated by mitochondrial hexokinase from brain when subjected to a variety of treatments. However, hexokinase activity was solubilized from preparations of mitochondria from the small intestine by the same treatments as for mitochondrial hexokinase from brain. 7. The submitochondrial distribution of hexokinase activity in mitochondrial preparations from rat brain was determined by the trypsin inactivation method. 8. Hexokinase activity in preparations of mitochondria from rat brain was found on the outside of the outer membrane, between the mitochondrial membranes, and within the inner mitochondrial membrane. 9. Hexokinase from rat brain showed latency properties irrespective of its submitochondrial location.
Biochem J 1971 Sep
PMID:Mitochondrial hexokinase from small-intestinal mucosa and brain. 513 35

A method has been developed for measuring the adhesion of platelets to purified collagen fibers obtained from bovine tendon. This method differs from others in that: (a) platelet adhesion is measured in the absence of platelet aggregation; (b) platelet-rich plasma collected in ACD (acid citrate dextrose) or EDTA, or washed platelets can be employed; (c) adherent platelets are enumerated directly; (d) erythrocytes and leukocytes do not adhere. Washed platelets suspended in human Ringer solution exhibit negligible adhesion (at the platelet concentrations employed) in contrast to washed platelets suspended in plasma. Addition of purified human fibrinogen (95% clottable, 2-4 mg/ml) to human Ringer solution completely restores the ability of washed platelets to adhere to collagen fibers. Albumin (fatty acid free, 50 mg/ml) is also capable of restoring adhesion. Albumin and seven other proteins at concentrations of 5-10 mg/ml, with varying molecular weights, isoelectric points, and frictional coefficients are incapable of supporting the adhesion of washed platelets. The proteins tested were human globulin, hexokinase, hemoglobin, cytochrome-C, insulin, thyroglobulin, and muramidase. Platelet adhesion is proportional to both platelet concentration and fibrinogen concentration, but is independent of temperature or glycogen stores. Modification of fibrinogen by acylation of amino groups or removal of sialic acid has no effect on its ability to support platelet adhesion. Degradation of fibrinogen with purified plasmin results in decreased support of platelet adhesion. This accompanied formation of early breakdown products with clottability ranging from 84-0%. Formation of fibrinogen degradation products was monitored by SDS-polyacrylamide gel electrophoresis of the corresponding fibrins after reduction of disulfide bonds (a method capable of distinguishing alpha-, beta- and gamma-chains). Decreased support of platelet adhesion is associated with the disappearance of intact alpha- chains and early modification of the beta-chains. Purified proteinpolysaccharide macromolecules obtained from bovine nasal and humeral cartilage, and from nucleosus pulposus are as effective as fibrinogen on a weight basis and ten to thirty times more effective on a molar basis in supporting platelet adhesion. The purified mucopolysaccharide side chains: chondroitin-4-sulfate, chondroitin-6-sulfate, and keratan-sulfate are incapable of supporting platelet adhesion.
J Clin Invest 1971 Sep
PMID:Biochemical and biophysical aspects of human platelet adhesion to collagen fibers. 556 92


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