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)

A theory is presented that associates burst (orlag) kinetics with the respective concentrations of enzyme initial states X1 and X6 and with the cooperation of a mnemonical enzyme. The theory predicts that for an enzyme with a negative cooperation, decreasing the initial concentration of X1 (or increasing that of X6) tends to increase the induction time. This increase may correspond to a reversal of a burst in a lag. Similarly, if the enzyme has a positive cooperation, decreasing the initial concentration of X6 (or increasing that of X1) increases the induction time. The first case above is expected to apply to wheat germ hexokinase LI, X1 being the form that binds glucose preferentially, and X6 the one that binds glucose 6-phosphate. By changing solely the respective concentrations of the two initial forms, one may expect to modify the pre-steady-state phase but not the steady-state kinetics of the reaction. By jumping the temperature of the enzyme solution from 4 degrees C to 30 degrees C and letting the transconformation ewuilibrium relax for various periods of time before mixing enzyme with the substrates, one can analyse the effect of the relative concentrations of X1 and X6 on the induction time. One can estimate in that way one of the rate constants of the transconformation between the two free enzyme forms. The shorter the incubation time at 30 degrees C then the smaller is the negative induction time (in absolute values). Another possibility of controlling the ratio between the two initial concentrations of the enzyme, is to pre-mix hexokinase with glucose 6-phosphate and to arrange that glucose-6-phosphate concentration, after mixing enzyme and substrates, is held constant whatever the pre-mixing conditions. When wheat germ hexokinase LI is pre-mixed 30 min at 30 degrees C with glucose 6-phosphate before the reaction starts, the burst does not disappear. If, on the other hand, pre-mixing is effected at 4 degrees C the burst is reversed into lag. This result is taken to mean that the equilibrium constant between the two free enzyme forms (the 'circle' and the 'rhombus') is strongly dependent on temperature. A direct study of the effect of glucose 6-phosphate on the conformational equilibrium of wheat germ hexokinase, gives support to this interpretation. If hexokinase is mixed at 4 degrees C with glucose 6-phosphate a slow increase in fluorescence of tryptophanyl residues is observed, which indicates that the 'rhombus' conformation accumulates under these conditions. On the other hand, at 30 degrees C, glucose 6-phosphate does not produce any significant change in the fluorescence of the protein. As expected, these results imply that the equilibrium between the two free enzymes species is freely reversible a 4 degrees C and nearly irreversible at 30 degrees C. The equations derived from the mnemonical model allow fitting or simulation of the experimental results.
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PMID:Enzyme memory. Effect of glucose 6-phosphate and temperature on the molecular transition of wheat-germ hexokinase LI. 46 32

Various enzymes of glycolysis (hexokinase, phosphoglucoisomerase, aldolase and lactate dehydrogenase), the Krebs cycle (isocitrate, succinic and malate dehydrogenases), and the pentose phosphate cycle (glucose-6-phosphate and 6-phosphogluconate dehydrogenases) were studied in buffalo spermatozoa by biochemical and cytochemical methods. The enzymes of glycolysis were found to be loosely bound whereas those of the Krebs and pentose phosphate cycles were strongly bound to mitochondrial membranes. All the enzymes studied were localized histochemically in the mid-piece.
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PMID:Glycolytic, Krebs cycle and pentose phosphate cycle enzymes in spermatozoa of the buffalo (Bubalus bubalis). 51 3

In leukocytes of exudate from diabetic rabbits, the activities of hexokinase, phosphoglucomutase and glucose-6-phosphate dehydrogenase are increased, and a tendency of adenylate kinase activity to decline is observable. The activities of UDP-pyrophosphatase, UDP-glycogentransferase, 6-phosphogluconate dehydrogenase and glutahione reductase in the exudate erythrocytes in diabetes are not essentially altered. The decrease of the key enzymes of glycolysis and pentose phosphate cycle, providing the leukocytes with energy and metabolites, reduces the functional activity of leukocytes from exudate in diabetes.
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PMID:[Enzyme profile of exudate leukocytes from diabetic rabbits]. 51 96

Mean levels of 2,3-diphosphoglycerate (DPG) were significantly increased in erythrocytes (RBC) from 43 nonanemic black blood donors (4.80 +/- 0.06 micromoles/l RBC) compared with 22 white donors 4.47 +/- 0.08 micromoles/l RBCs from eight of the 12 black donors with DPG levels greater than 5 micromoles/l RBC. Although a potentially hemolytic disorder could be defined in four (AS hemoglobin, beta-Thalassemia minor, G6PD deficiency), reticulocyte counts were normal. However, when RBCs from the subgroup were compared to RBCs from an additional 25 unselected white donors, the following suggested an abnormally large population of young RBCs in the subgroup: 1) normal or elevated RBC-ATP with normal serum phosphate level; 2) significantly increased activities of RBC age-dependent enzymes hexokinase (p less than 0.02), pyruvate kinase (p less than 0.05), and glutamicoxaloacetic transaminase (p less than 0.01), with normal activity of phosphoglycerate kinase, an age-independent enzyme; 3) decreased dense (older) RBCs as determined by sedimentation in phthalate esters. Since DPG is increased in young RBCs and falls as the RBC ages, loss of older relatively DPG depleted RBCs due to shortened survival could account for the elevated DPG levels seen in the subgroup.
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PMID:Elevated red blood cell 2,3-diphosphoglycerate levels in black blood donors. 62 75

Untrained healthy male volunteers were studied to observe the effects of physical exercise (bicycle ergometer, 920 kpm/min for 10 min, 15 min and 30 min) upon glycolytic intermediates in red blood cells. The levels of glucose 6-phosphate, fructose 6-phosphate, pyruvate and lactate increased after each exercise. The levels of fructose 1,6-diphosphate increased and phosphoenolpyruvate decreased respectively only after 30 min of exercise. At the rest period of 30 min after 30 min of exercise the lactate level still remained unchanged, however all the other intermediates returned to the preexercise values. A negative crossover point seemed to exist between fructose 6-phosphate and fructose 1, 6-diphosphate after 15 min of exercise. A positive crossover point was observed between phosphoenolpyruvate and pyruvate after 30 min of exercise. There were significant increases in hexokinase and pyruvate kinase activities, but not in phosphofructokinase activity after 30 min of exercise. These facts suggested that the increase in pyruvate kinase activity was due to the elevated fructose 1,6-diphosphate level after 30 min of exercise. A significant increase in plasma dopamine-beta-hydroxylase activity was found after each exercise. A close positive correlation was observed between pyruvate-phosphoenolpyruvate ratio and dopamine-beta-hydroxylase activity after 30 min of exercise. It was suggested that pyruvate-phosphoenolpyruvate ratio provided a reliable index of physical exercise.
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PMID:[Effect of physical exercise on glycolysis in human red blood cells (author's transl)]. 71 Nov 26

1. The specific activity of yeast hexokinase A depends on the concentration of the protein in the solution being assayed. When a solution containing 13.5 mg of hexokinase A/ml is diluted 10--100-fold at various values of pH and temperature, there is a gradual decline in the specific activity of the enzyme until an equilibrium value is reached, which varies with the chosen experimental conditions. 2. The catalytic activity lost when hexokinase A (1 mg/ml) is incubated at 30degreesC is recovered by lowering the temperature to 25degreesC. 3. These concentration- and temperature-dependent phenomena are consistent with the existence of a monomer-dimer equilibrium in which the dimer alone is the catalytic form of the enzyme. 4. Glucose alone prevents the decline in specific activity of hexokinase A after dilution, but it does not re-activate dilute solutions solutions of the enzyme. It is concluded that glucose binds to both the dimer and the monomer and prevents both association and dissociation. 5. The progress curve describing the phosphorylation of glucose catalysed by hexokinase A does not attain a steady state. It is possible that dissociation of catalytically active dimers in a ternary complex with glucose and ATP (or glucose 6-phosphate and ADP) could explain the non-linearity of this progress curve.
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PMID:Dissociation and catalysis in yeast hexokinase A. 78 48

The Mg2+ precipitation procedure of R. D. Palmiter ((1974) Biochemistry 13, 3606) has been used for preparative scale isolation of polysomes from Ehrlich ascites mitochondria. Digitonin-washed metochondria used for isolating the polysomes contain no detectable reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase and over 200-fold reduced hexokinase activity. The mitochondrial polysomes exhibit a heterogeneous sedimentation and appear to contain highly aggregated particlses ranging over hexamers. These polysomes are sensitive to RNase, (ethylenedinitrilo)tetraacetic acid and puromycin. Mitochondrial polysomes are active in portein synthesis when supplied with supernatant enzymes from the homologous mitochondrial source or from Escherichia coli. Cytoplasmic enzymes, however, appear to be completely inactive. Protein synthesis by mitochrondrial polysomes is sensitive to chloramphenicol and resistant to cycloheximide and emetine. The procedure yields particles containing intact rRNAs. The extent of cytoplasmic RNA contaminating the total mitochondrial RNA or mitochondrial polysomal RNA has been estimated to be negligible.
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PMID:Messenger ribonucleic acid metabolism in mammalian mitochondria. Isolation and characterization of polyribosomes from Ehrlich ascites mitochondria. 82 18

The uptake and phosphorylation of 2-deoxy-D-glucose by isolated adipocytes of the rat was determined by a method of rapid flotation through oil coupled with separation of sugar from sugar phosphate by chromatography on Dowex-1-formate. Uptake of the sugar is rapid and linear over 5 min, with a gradual decline thereafter; by 1 h, no further uptake is observed. Initially only 2-deoxy-glucose phosphate is observed within the cells; by 1 h, however, free 2-deoxy-glucose accumulates to levels approximately those in the medium. Phosphorylation ceases when intracellular levels of 2-deoxyglucose phosphate are about 50 mM regardless of the medium concentration of 2-deoxyglucose; this does not represent feedback inhibition of hexokinase, since the enzyme in fat cell homogenates is not inhibited by 50 mM 2-deoxyglucose 6-phosphate. Accumulation of deoxyglucose 6-phosphate is associated with a marked decline in intracellular ATP levels. Fat cell respiration is also depressed by approximately 50 per cent after a 1 h preincubation with 10 or 20 mM 2-deoxyglucose. Intracellular ATP levels and O2 uptake are only partially corrected by the addition of pyruvate to the incubation medium. Since no glucose was present in the medium, and intracellular concentrations of glycogen are known to be small in adipose tissue, it is proposed that accumulation of 2-deoxyglucose 6-phosphate within fat cells has a direct inhibitory effect on cell respiration unrelated to inhibition of glycolysis. No increase in intracellular free fatty acids was observed to explain this, and under the conditions of the incubations it is unlikely that Pi availability was rate limiting. The exact locus of inhibition is unknown.
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PMID:Metabolic effects of 2-deoxy-D-glucose in isolated fat cells. 83

1. The development of pyruvate dehydrogenase and citrate synthase activity in rat brain mitochondria was studied. Whereas the citrate synthase activity starts to increase at about 8 days after birth, that of pyruvate dehydrogenase starts to increase at about 15 days. Measurements of the active proportion of pyruvate dehydrogenase during development were also made. 2. The ability of rat brain mitochondria to oxidize pyruvate follows a similar developmental pattern to that of the pyruvate dehydrogenase. However, the ability to oxidize 3-hydroxybutyrate shows a different developmental pattern (maximal at 20 days and declining by half in the adult), which is compatible with the developmental pattern of the ketone-body-utilizing enzymes. 3. The developmental pattern of both the soluble and the mitochondrially bound hexokinase of rat brain was studied. The total brain hexokinase activity increases markedly at about 15 days, which is mainly due to an increase in activity of the mitochondrially bound form, and reaches the adult situation (approx. 70% being mitochondrial) at about 30 days after birth. 4. The release of the mitochondrially bound hexokinase under different conditions by glucose 6-phosphate was studied. There was insignificant release of the bound hexokinase in media containing high KCl concentrations by glucose 6-phosphate, but in sucrose media half-maximal release of hexokinase was achieved by 70mum-glucose 6-phosphate 5. The production of glucose 6-phosphate by brain mitochondria in the presence of Mg(2+)+glucose was demonstrated, together with the inhibition of this by atractyloside. 6. The results are discussed with respect to the possible biological significance of the similar developmental patterns of pyruvate dehydrogenase and the mitochondrially bound kinases, particularly hexokinase, in the brain. It is suggested that this association may be a mechanism for maintaining an efficient and active aerobic glycolysis which is necessary for full neural expression.
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PMID:Development of mitochondrial energy metabolism in rat brain. 88 Feb 41

Activity of hexokinase, phosphorylase, glucoso-6-phosphate dehydrogenase lactate-dehydrogenase was studied in liver slices, homogenate and supernatant fraction after freezing at a rate of 1 degree/min down to -30 degrees C. The enzyme activity in homogenate and supernatant fraction does not change after freezing. A significant reduction in the activity of most enzymes that is followed by an increase in their activity in the freezing medium was observed in the experiments. Cryoprotectant polyethylene glycol, mol. wt. 300 and 1,000 (PEG-300 and PEG-1,000), partially prevents the observed changes in the enzyme activity; PEG-1,000 is more effective than PEG-300. Experimental results show that the main reason for the reduction of the enzyme activity observed after freezing the tissue slices is a decrease in the volume of intracellular enzyme proteins due to their leakage from the injured cellular elements into the exocellular medium.
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PMID:[Activity of carbohydratephosphate metabolism enzymes in liver slices after freezing and thawing]. 88 19


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