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 control theory of steady states, previously presented for linear enzymatic systems (Heinrich and Rapoport, 1974) is extended to nonlinear systems. On the basis of three theorems a new procedure for the calculation of the control strength and of the control matrix is developed. The theory is applied to the extended model of glycolysis of erythrocytes, which includes also ATP-consuming processes. Also in this model the glycolytic flux is mainly controlled by the hexokinase-phosphofructokinase-system. The control strengths of the pyruvate kinase and of the enzymes of the 2.3 P2G-bypass are negligibly small. The control strength of the ATPase is negative, i.e. an activation of this enzyme leads to a decrease of the flux. For transition states of multienzyme systems definitions are given for the mean time required for the transition of the metabolites and for the "transient control" of enzymes. Enzymes with a pronounced influence on the transition time are called time-limiting enzymes. Enzymes which excert strong control on the time-dependent processes may have little influence under steady state conditions and vice versa. The transition times of ATP have been calculated for transient states of glycolysis.
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PMID:Mathematical analysis of multienzyme systems. II. Steady state and transient control. 12 16

We decribed the preparation of adenine 1-oxide nucleotides by oxidation of the natural compounds with monopermaleic acid in aqueous solutions at neutral pH, with an overall yield after chromatographic purification between 75 and 80%. If irradiated, the adenine 1-oxide nucleotides undergo a photochemical rearrangement reaction, the main photoproducts in aqueous solution at alkaline pH being the corresponding isoguanine nucleotides. The modified ring vibration pattern of the 1-oxide analogues as well as the 13C chemical shift indicate a loss of aromaticity as compared to the natural compounds. Coupling constant measurements show that the dihedral angle between the 31POC and OC13C planes is around 180degree, i.e., trans, as in the natural adenine nucleotides. The modified adenine nucleotides were tested as potential substrates and/or inhibitors of mitochondrial processes, as substrates of varous phosphotransferases from mitochondria or cytosol, and as allosteric effectors in the reactions catalyzed by glutamate dehydrogenase and phosphofructokinase. Although the adenine 1-oxide nucleotides are not recognized by the translocase system of the inner mitochondrial membrane, they are good substrates for mitochondrial phosphotransferases located in the intermembrane space. Similarly, they participate in the phosphoryl group transfer reactions catalyzed by pyruvate kinase, phosphofructokinase, and hexokinase. As allosteric effectors, the modified nucleotides are less active than the natural compounds, probably because of a lower binding capacity to the allosteric sites of the regulatory enzymes.
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PMID:Structural and enzymatic properties of adenine 1-oxide nucleotides. 12 77

Specimens of human adipose tissue were cultured for one week with or without the addition of insulin. The basal as well as the noradenaline-stimulated lipolysis were enhanced in the explants cultured with insulin, showing that the long-term effect of the hormone is lipolytic. However, an acute antilipolytic effect of insulin could be demonstrated in these explants in the subsequent short-term incubations. The basal rate of glucose incorporation into the lipids was enhanced in the explants cultured with insulin. When insulin was added in the short-term incubations these explants did not further respond to the hormone while this was the case with the explants cultured without insulin. Thus, it seems that prolonged exposure to insulin leads to a diminished acute effect of the hormone on glucose metabolism. However, the same explants responded to the antilipolytic effect showing that insulin was able to bind itself to the membrane. The activities of hexokinase (HK), glucose-6-phosphage dehydrogenase (G6PDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) were increased in large fat cells both in freshly excised tissue and in cultured explants. However, the activity of phosphofructokinase (PFK) did not correlate with the cell size. The presence of insulin during the culture period enhanced the activities of G7PDH, PK, and LDH, while this was not found for HK or PFK. The data thus suggest that the metabolic capacity of human fat cells is enhanced by long-term exposure to insulin. Although enzyme induction could be shown for G6PDH, PK and LDH it seems unlikely that this is of importance for the increased rates of glucose metabolism in these explants since the rate-limiting enzymes, HK and PGK, were not increased. Most probably, then, this stimulating effect of insulin is exerted on the membrane and the rate of glucose transport.
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PMID:Human adipose tissue in culture V. Studies on the metabolic effects of insulin. 13 27

A simple mathematical model for glycolysis in erythrocytes is presented which takes into account ATP synthesis and consumption. The system is described by four ordinary differential equations. Conditions in vivo are described by a stable steady state. The model predicts correctly the metabolite concentrations found in vivo. The parameters involved are in agreement with data on the separate steps. The metabolite changes found in pyruvate kinase-deficient erythrocytes and the species variations among erythrocytes from different animals are described satisfactorily. The roles of the enzymes in the control of metabolites and glycolytic flux are expressed in the form of a control matrix and control strengths [R. Heinrich & T.A. Rapoport (1974) Eur. J. Biochem. 42, 89-95] respectively. Erythrocytes from various species are shown to be adapted to a maximal ATP-consumption rate. The calculated eigenvalues reveal the pronounced time-hierarchy of the glycolytic reactions. Owing to the slowness of the 2,3-bisphospho-glycerate phosphatase reaction, quasi-steady states occur during the time-interval of about 0.5-2h incubation, which are defined by perturbed 2,3-bisphosphoglycerate concentrations. The theoretical predictions agree with experimental data. In the quasi-steady state the flux control is exerted almost entirely by the hexokinase-phosphofructokinase system. The model describes satisfactorily the time-dependent changes after addition of glucose to starved erythrocytes. The theoretical consequences are discussed of the conditions in vitro with lactate accumulation and the existence of a time-independent conservation quantity for the oxidized metabolites. Even in this closed system quasi-steady states occur which are characterized by approximately constant concentrations of all glycolytic metabolites except for the accumulation of lactate, fructose 1,6-bisphosphate and triose phosphate.
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PMID:The regulatory principles of glycolysis in erythrocytes in vivo and in vitro. A minimal comprehensive model describing steady states, quasi-steady states and time-dependent processes. 13 30

1. Cataract formation in streptozotocin-induced diabetes in rats was reduced by approximately 85% when a diet rich in maize oil (300 g/kg diet) (fat diet) was given, thus confirming results of earlier studies. However, the concentration of sorbitol in the lens of diabetic animals remained high, the values for diabetic rats given the standard diet and the fat died being 65 and 40 mumol/g protein respectively. 2. With the standard diet, the fatty acid profile of the triglycerides of the epididymal fat pads was characterized by a greater relative proportion of saturated fatty acids for the diabetic animals compared to that for the normal animals. The fat diet moderated the tendency towards saturation in the diabetic animals. 3. The fat diet had other effects on the diabetic animals; these included a reduced mortality rate, increased body-weight, a decrease in the daily water intake, and in the daily urinary excretion of glucose and urea. 4. In the diabetic animals the fat diet had no effect on the specific activities in the liver of hexokinase (EC 2.7.1.1), glucokinase (EC 2.7.1.2), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40). However, the specific activity of glucose-6-phosphatase (EC 3.1.3.9) was reduced, while that of malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) was increased. The NAD+:NADH ratio, as calculated from liver pyruvate and lactate concentrations, tended to increase. 5. The results suggested that the fat diet moderated the long-term metabolic effects of diabetes.
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PMID:The effect of an unsaturated-fat diet on cataract formation in streptozotocin-induced diabetic rats. 13 11

The activities of several glycolytic enzymes (hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase) as well as glycerol-1-phosphate dehydrogenase and (Mg2+)ATPase in normal cerebrospinal fluid (CSF) and blood plasma samples, from 12 healthy infants, aged 2-18 months, and in supernatants from brain tissue slices, taken during neurosurgical operations from infants of the same range of age were estimated. The values obtained confirm the high activity of the above enzymes found in animal brains, and indicate an independence of these activities in blood plasma and CSF. The origin of the activities of the investigated enzymes in CSF seems to be mainly, if not, exclusively, from brain tissue. This might be useful for detection of brain tissue damage as was earlier proven with LDH activity in CSF.
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PMID:Some glycolytic enzymes in normal cerebrospinal fluid, brain tissue and blood plasma of infants. 13 54

By addition of enzyme the control intensity was determined on the pacemaker enzymes hexokinase and phosphofructokinase, as well as on glyceraldehyde-3-phosphate-dehydrogenase and the pyruvate kinase with a control intensity of almost 0 in ultrasonic hemolysates from erythrocyte concentrate. This hemolysate approximately reflects the conditions existing in the intact cell with regard to glycolytic rate, ATP supply, and metabolite concentration. It is therefore suitable as a cell model, excluding the membrane, for studying inner control factors. For HK, PFK, GAPD, and PK predictions based on the linear glycolytic model about the significance of these enzymes for the regulation of the glycolytic rate could be confirmed.
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PMID:[Control intensity of glycolytic enzymes in ultrasonic hemolysates of erythrocytes]. 13 59

The characteristics of the glycolytic pathway and the plasma membrane of Lactobacillus and Bifidobacterium were studied. The enzyme system of glycolysis (hexokinase, glucokinase and pyruvate kinase) which is the main source of energy in the anaerobic condition was localized in the cell soluble fraction (cytoplasma) of all species examined. Neither electron transfer chain components nor oxidase activities were found in anaerobically cultured Lactobacillus and Bifidobacterium. Adenosine triphosphatase (ATPase) activities were mainly localized in the plasma membrane, suggesting that membrane ATPase is playing a key role in membrane transport and ATP synthesis of anaerobic bacilla. SDS-polyacrylamide gel electrophoresis of membranes showed remarkable differences between the polypeptides patterns of B. adolescentis and B. bifidum. Such peculiarities in polypeptide patterns among the same genus may be useful in the identification of species.
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PMID:Characterization of the glycolysis pathway and the plasma membrane of Lactobacillus and Bifidobacterium strains. 13 31

Adipose tissue and liver from vitamin B6-deficient rats have an increased lipogenic capacity. Whether this phenomenon is accompanied by changes in the activities of certain enzymes involved in the metabolism of carbohydrate and lipid, or by altered transport of glucose into adipocytes, has been studied. Five glycolytic enzymes (hexokinase, phosphoglucose isomerase, phosphofructokinase, aldolase, and pyruvate kinase), two pentose phosphate pathway enzymes (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), malic enzyme, and ATP citrate lyase were measured in the epididymal adipose tissue, livers and kidneys of vitamin B6-deficient and control rats. Vitamin B6 deficiency did not significantly affect the glycolytic enzyme levels in the tissues studied, or the dehydrogenases measured in adipose tissue and kidneys. Liver glucose-6-phosphate dehydrogenase, and adipose tissue and liver malic enzyme were significantly lowered in deficient rats compared to ad libitum and pair-fed controls. Adipose tissue and liver ATP citrate lyase activities were also significantly decreased by vitamin B6 deficiency. In the presence of insulin, the uptake of glucose and 3-O-methyl glucose, a non-metabolizable sugar, by fat pads from deficient rats was greater than uptake by fat pads from control rats. These observations suggest that the increased glucose utilization by adipose tissue and liver of vitamin B6-deficient rats is not directly related to changes in the enzymes studied, but in the case of adipose tissue, may be explained, at least in part, by enhanced glucose uptake.
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PMID:Effects of vitamin B6 deficiency on liver, kidney, and adipose tissue enzymes associated with carbohydrate and lipid metabolism, and on glucose uptake by rat epididymal adipose tissue. 13 63

The influence of clofibrate on the glycolytic pathway in liver was studied. The changes in the activity of glucokinase and hexokinase were not significant. A reduction of phosphofructokinase (p less than 0.05) and pyruvate kinase activity was found (p less than 0.0005) during clofibrate feeding. An in vitro inhibition of these enzymes could not be demonstrated by clofibrate up to a concentration of 2.5 mM. Crossover plots of glycolytic intermediates indicate that the reduced pyruvate kinase activity may influence the glycolytic pathway in vivo. Clofibrate feeding induces a lower ATP:ADP ratio, a lower adenylate energy charge and elevates AMP levels in rat liver. This may possibly stimulate the hepatic glycogenolysis and the glucose utilisation by this organ.
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PMID:Alterations of the glycolytic pathway and adenine nucleotide state in livers of clofibrate treated rats. 14 Aug 42


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