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)

1) In intact Ehrlich ascites tumour cells the anaerobic glycolytic flux rate and pattern of intermediates have been investigated at different pH values of the extracellular medium. 2) As predicted from the dependence of the lactic acid dehydrogenase equilibrium on pH a strong negative correlation between log ([lactate]/[pyruvate]) and pH has been found. 3) The steady state fluxes of glycolysis at pH 8.0 and 7.4 are rather equal, despite significant differences in the intracellular concentrations of glycolytic intermediates. At pH 8.0 the concentrations of ATP, glucose 6-phosphate, and fructose 6-phosphate are lower, and the concentrations of ADP, AMP, fructose 1,6-bisphosphate, triose phosphates, phosphoglycerates, and phosphoenolpyruvate are higher than at pH 7.4. 4) From the analysis of the pH dependent changes of metabolites it follows that different mechanisms are responsible for maintaining equal actual activities of hexokinase, phosphofructokinase and pyruvate kinase at pH 7.4 and 8.0. 5) From an application of the linear theory of enzymatic chains and a calculation of the control strength of the regulatory important enzymes results that hexokinase is evidently rate-limiting for glycolysis, and phosphofructokinase is also significantly influencing the glycolytic flux. Pyruvate kinase and glyceraldehyde phosphate dehydrogenase, on the other hand, do not significantly affect the rate of the overall glycolytic flux in ascites.
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PMID:Regulation of anaerobic glycolysis in Ehrlich ascites tumour cells. 2 29

Clinical and hematological studies were performed on ten homozygous and seven heterozytous individuals with pyruvate kinase deficiency, aged between 2 and 71 years. Five of the homozygotes were splenectomized. With the exception of a decreased enzyme activity between 41 and 55 per cent and minor changes in their red cell metabolism the heterozygotes showed no abnormal results. In the homozygotes the following results could be demonstrated: 1. Pyruvate kinase activity was decreased to 11 to 35 per cent of normal enzyme activity. 2. There is no relation between the severity of hemolysis and the degree of the enzyme defect. 3. The reticulocyte counts correlated inversely with the hemoglobin concentrations. 4. There is a close correlation between the activities of hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase and glutamate oxalacetate transaminase on the one side and reticulocyte counts on the other. 5. Adenosine triphosphate or adenosine reduced the increased autohemolysis in all cases. 6. Following splenectomy, anemia was less pronounced than before. Splenectomized patients did not need further transfusions, though hemolysis persisted.
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PMID:[Pyruvate kinase deficiency. I. Clinical and hematological observations (author's transl)]. 12 93

The present study examined the effect of vanadate on the activity of key enzymes of glycolysis and the level of fructose 2,6-bisphosphate (F-2, 6-P2) in the hearts of diabetic rats. A 20% decrease in the total hexokinase activity and 66% decrease in the type II isoenzyme was found in diabetic rat hearts. Vanadate treatment doubled the activity of type II hexokinase. Pyruvate kinase and phosphofructokinase 1 activity was reduced by 20% in diabetes, vanadate treatment restored the activity of the enzymes to normal. A 43% decrease in the cardiac F-2, 6-P2 level was found in diabetes of four weeks duration. A significant inverse correlation between blood glucose of experimental animals and the level of heart F-2, 6-P2 was observed. Vanadate treatment doubled the amount of F-2, 6-P2 in diabetic rat hearts.
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PMID:Vanadate treatment increases the activity of glycolytic enzymes and raises fructose 2,6-bisphosphate concentration in hearts from diabetic rats. 148 92

As a common characteristic of tumor cells, as well as of normal proliferating cells in the G1-phase of cell cycle, one finds constitutive high levels of all the glycolytic metabolites arising between glucose 6-phosphate and phosphoenolpyruvate. Thus, it is that the phosphometabolites fructose 1,6-bisphosphate, ribose 5-P, P-ribose-PP, NAD, GTP, CTO, UTP, UDP-glucose, glycerol 3-P, glycerol phosphocholine and glycerol phosphoethanolamine are useful in the 31P-nuclear magnetic resonance (NMR) detection of solid tumors in animals and man. This expansion of phosphometabolites is achieved during tumor formation as a result of reductions in levels of enzymes degrading phosphometabolites, owing to the decline in the glycerol 3-P hydrogen shuttle, and as a consequence of alterations in the glycolytic isoenzyme equipment. Tumor cells typically express a particular isoenzyme of pyruvate kinase called type M2 (K) at high levels. This isoenzyme is subject to a complex regulation by amino acids, by fructose 1,6-bisphosphate, and by hormonal- and oncogene-dependent phosphorylation. Pyruvate kinase type M2 is a substrate for the oncogene encoded PP60v-src-tyrosine kinase. A drastic decrease in the affinity for its substrate phosphoenolpyruvate found after transformation by the src-oncogene can be explained as a consequence of the phosphorylation of pyruvate kinase in serine and tyrosine. These phosphorylations induce the breakdown of tetrameric pyruvate kinase to the trimeric and dimeric forms. Unlike the tetrameric form, the dimeric form as a low affinity for phosphoenolpyruvate. Partial inactivation of pyruvate kinase and enolase on the one hand, and a hyperactivation of hexokinase and phosphofructokinase on the other hand, lead to an expansion of all metabolites. Only when these metabolites attain high levels, thereby assuring a sufficient supply of metabolites for RNA, DNA, lipid, and complex carbohydrate synthesis, can cell proliferation proceed. This accumulation of metabolites in the G1-phase cells has been termed a "metabolic budget system" because it senses not only the actual nutrient levels, but also the supply over a period of time. Monoclonal antibodies specific for the dimeric form of pyruvate kinase type M2 can be used for the immunohistological detection of tumor cells. The amount of the dimeric form in tumor cells closely correlates with the degree of malignancy and can be used for a nonspecific detection of tumors based on assays performed with patient's plasma.
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PMID:Double role for pyruvate kinase type M2 in the expansion of phosphometabolite pools found in tumor cells. 153 31

Most of the enzymes involved in glycolysis are readily reversible and are also active in gluconeogenesis. However, three reaction steps are irreversible, i.e., those catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase; for in each of these reactions there occurs a large negative free-energy change, and these are reactions thus bypassed by alternate enzyme-catalyzed reactions. Pyruvate kinase (EC 2.7.1.40, PK) plays an important role in controlling glycolysis and gluconeogenesis. To clarify the characteristics of glycolysis in dental pulp, we examined the enzymatic properties of pyruvate kinase from pig dental pulp and compared them with those of the enzyme from pig brain. 1) Pyruvate kinase from dental pulp and brain were purified by use of ammonium sulphate fractionation, phosphocellulose colum chromatography, and isoelectric focusing. The prepared enzymes showed a single protein band on SDS polyacrylamide gel electrophoresis. 2) The subunit molecular weight of dental pulp and brain enzymes was determined to be 63,000 and 59,000, respectively. 3) Substrate inhibition of dental pulp and brain enzymes by phosphoenolpyruvate was not observed, and the relationship between reaction velocity and substrate concentration at pH 7.2 was explained by the Michaelis-Menten equation. Fructose-1,6-diphosphate had no observable effect on either enzyme. 4) Effect of amino acids on dental pulp and brain enzyme activity were examined, and no significant relationship was observed between the side chain structure of amino acids and their potency in inhibiting dental pulp and brain enzyme activity. Glutamic and aspartic acids markedly inhibited dental pulp and brain enzymes at pH 7.2. 5) Oxalate showed inhibitory activity against dental pulp and brain enzymes, and the Ki value was determined to be 50 microM and 80 microM, respectively. The inhibition of dental pulp and brain enzyme activity by oxalate was competitive with respect to phosphoenolpyruvate. 6) Both dental pulp and brain enzymes were clearly inhibited by malate at concentrations higher than 1.0 mM: 50% and 100% inhibition occurred at 2.2-2.3 mM and 3.0 mM malate, respectively.
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PMID:[Studies on pyruvate kinase from pig dental pulp and brain]. 198 6

Erythrocytes were separated by age using a combination of density centrifugation and counterflow centrifugation and tested for basal activity of the hexose monophosphate shunt (HMP-shunt) as well as the methylene blue-stimulated maximal capacity by measuring CO2 production. No significant differences were found in basal HMP-shunt activity, but the maximal methylene blue-stimulated activity of old erythrocytes reached only half of the activity of the total cell population. The maximal HMP-shunt activity showed a significant correlation with hexokinase activity, but not with glucose-6-phosphate dehydrogenase activity in all but the youngest cells. The sensitivity to oxidative stress was tested by measuring the kinetics of pyruvate kinase isolated from erythrocytes incubated in presence and absence of methylene blue. Pyruvate kinase kinetics were affected more in the old cell population than in the total cell population: the K0.5 for phosphoenol-pyruvate increased four times in the unseparated cells and eight times in old cells.
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PMID:Hexose monophosphate shunt activity in erythrocytes related to cell age. 261 18

Activity changes of a number of enzymes involved in carbohydrate metabolism were determined in cell extracts of fractionated exponential-phase populations of Saccharomyces cerevisiae grown under excess glucose. Cell-size fractionation was achieved by an improved centrifugal elutriation procedure. Evidence that the yeast populations had been fractionated according to age in the cell cycle was obtained by examining the various cell fractions for their volume distribution and their microscopic appearance and by flow cytometric analysis of the distribution patterns of cellular DNA and protein contents. Trehalase, hexokinase, pyruvate kinase, phosphofructokinase 1, and fructose-1,6-diphosphatase showed changes in specific activities throughout the cell cycle, whereas the specific activities of alcohol dehydrogenase and glucose-6-phosphate dehydrogenase remained constant. The basal trehalase activity increased substantially (about 20-fold) with bud emergence and decreased again in binucleated cells. However, when the enzyme was activated by pretreatment of the cell extracts with cyclic AMP-dependent protein kinase, no significant fluctuations in activity were seen. These observations strongly favor posttranslational modification through phosphorylation-dephosphorylation as the mechanism underlying the periodic changes in trehalase activity during the cell cycle. As observed for trehalase, the specific activities of hexokinase and phosphofructokinase 1 rose from the beginning of bud formation onward, finally leading to more than eightfold higher values at the end of the S phase. Subsequently, the enzyme activities dropped markedly at later stages of the cycle. Pyruvate kinase activity was relatively low during the G1 phase and the S phase, but increased dramatically (more than 50-fold) during G2. In contrast to the three glycolytic enzymes investigated, the highest specific activity of the gluconeogenic enzyme fructose-1, 6-diphosphatase 1 was found in fractions enriched in either unbudded cells with a single nucleus or binucleated cells. The observed changes in enzyme activities most likely underlie pronounced alterations in carbohydrate metabolism during the cell cycle.
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PMID:Changes in activities of several enzymes involved in carbohydrate metabolism during the cell cycle of Saccharomyces cerevisiae. 284 28

The activities of the rate-limiting enzymes of glycolytic pathway were measured in various areas of rat brains kept at a temperature of +25 degrees C for various intervals after death by cervical dislocation. Hexokinase shows a substantial decline in activity over a period of 24 h, reaching 41%, 57%, 44%, and 51% of the controls in cerebellum, medulla oblongata and pons, cerebral cortex, and diencephalon, respectively. In the same areas the phosphofructokinase reached 28%, 61%, 60%, and 40% of the zero-time activity, respectively. Lactate dehydrogenase behaves differently in the four areas, with an increase in cerebral cortex and diencephalon and a decrease in cerebellum and medulla oblongata and pons. Pyruvate kinase activity was quite stable over the 24 h period studied. Therefore, the activities of hexokinase and phosphofructokinase in brain tissue were of little value for diagnosis of the time of death.
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PMID:Postmortem activity of the key enzymes of glycolysis. In rat brain regions in relation to time after death. 294 19

The effect of fatigue (running to exhaustion) on the Vmax activity of the key glycolytic enzymes measured at saturating substrate concentrations in muscles, liver and brain of sedentary and trained (running on a treadmill one h/day at 20 m/min, five days/week for six months) female Zucker fatty rats and their lean littermates was investigated. In the sedentary rats, fatigue increased the activity of phosphofructokinase (PFK) in the red vastus muscle by 82% in lean, and 120% in obese rats. In the trained rats, fatigue increased PFK activity by 28% in the white vastus muscle of lean rats. In the lean animals, hexokinase (HK) activity was decreased by 26% in the red vastus of sedentary rats, and by 29% in the white vastus of trained rats upon fatiguing. Pyruvate kinase (PK) activity was also decreased by 29% in the white vastus of fatigued lean animals. Training by itself had no effect on the activity of glycolytic enzymes, except PK activity which was increased by 27% in the cortex of the lean animals. It is concluded that in the Zucker rat, these glycolytic enzymes may play a differential role in regulating glycolysis during exercise and fatigue; the extent of their involvement differs depending upon the type of tissue studied and exercise. In view of the reported short half-life (7-17 h) of PFK and its covalent modification, it is suggested that the total content and/or phosphorylation status of the enzyme may be affected in animals subjected to long-term fatigue.
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PMID:Effect of exercise on glycolytic enzymes of Zucker fatty rats. 297 74

Glucose utilization by different metabolic pathways in bovine adrenal medulla has been studied using freshly isolated adrenal chromaffin cells. The rate of net glucose utilization in resting cells was 10.5 mumoles X g-1 X h-1. 50% was transformed into lactate and pyruvate, the lactate to pyruvate ratio ranging from 3 to 7.27% was metabolized through the tricarboxylic acid cycle and 3.1% was oxidized in the pentose phosphate pathway. The ratio of 14CO2 production from [1-14C] glucose and [6-14C] glucose was close to 2 at one hour of incubation. 3.2% of total glucose consumed was used in protein synthesis, and 1% was incorporated into lipids. Oxygen utilization in respiration by isolated adrenal chromaffin cells was 18.2 mumoles X g-1 X h-1, corresponding to 3.1 mumoles glucose X g-1 X h-1 or about 30% of total glucose consumed. The activities of hexokinase, enolase, pyruvate kinase, lactate dehydrogenase, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were assayed in extracts of bovine adrenal medulla, being 1.0, 23, 40, 37, 6.0 and 3.0 U/g respectively. Hexokinase activity was identified as belonging mainly to isoenzyme I, with some isoenzyme II. Enolase was predominantly the alpha gamma hybrid. Pyruvate kinase activity corresponded to a mixture of isoenzymes K and M. Lactate dehydrogenase activity corresponded to isoenzymes 1, 2 and 3, with smaller proportions of isoenzymes 4 and 5. Results are discussed mainly with respect to those reported for the brain.
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PMID:Enzymes and pathways of glucose utilization in bovine adrenal medulla. 371 7


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