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)

Sodium fluoride was inadvertently added as a preservative to the urine of an eight-year-old boy with diabetes mellitus before urinary glucose was measured. On preliminary screening of the urine, the test by glucose oxidase paper reagent strip gave a negative reading for glucose, whereas quantitative urinary glucose assay by the coupled enzyme reaction (hexokinase-glucose 6-phosphate dehydrogenase) gave a glucose concentration of 81.5 g/liter. Inadvertent use of sodium fluoride as a urine preservative may cause a falsely negative result with the glucose tests involving oxidase.
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PMID:Inhibitory effect of fluoride on glucose tests with glucose oxidase strips. 113 42

1. Pigeon erythrocyte was found to depend on the glycolytic and pentose phosphate pathway for most of its energy production in the form of adenosine triphosphate and reducing potential, since there was no detectable activity of any of the citric acid cycle (TCA) cycle enzymes measured. 2. The absence of detectable amounts of 2,3-diphosphoglyceric acid (2-3-DPG) indicated that there is no direct relationship between the active glycolytic system and the function of these cells. 3. A comparison of the mass action ratios with the equilibrium constants of the glycolytic reactions showed that hexokinase, phosphofructokinase and pyruvate kinase reactions are displaced from equilibrium, implying that these are the key regulatory enzymes of glycolysis in pigeon erythrocytes. 4. The changes in the concentrations of the glycolytic metabolites under hypoxic conditions that stimulate the flux through the glycolytic pathway were found to be consistent with the above hypothesis. 5. Flux measurements of the pentose phosphate pathway showed that it metabolizes only 3.4% of the total glucose consumed by the resting erythrocyte. 6. Hypoxic conditions resulted in a stimulation of the pentose phosphate pathway by as much as four-fold, whilst the glycolytic pathway was not stimulated by more than about twice.
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PMID:Studies on the pigeon red blood cell metabolism. 234 29

Flux control coefficients of hexokinase for glucose metabolism in different rat tissues have been determined, showing that the hepatocyte cytosolic hexokinase is the only one which plays an important role in the control of the glucose-input flux studied among the different tissues. Explanation of these results are given in terms of the kinetics features of hexokinase and the metabolic role of glucose in these tissues.
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PMID:Role of hexokinase in controlling the glucose metabolism flux: a study of its flux control coefficient in different tissues. 270 51

Control of flux and transition time was investigated with a reconstructed rabbit muscle glycolytic system in vitro as an experimental model. The results show agreement with the summation property for the Flux Control Coefficients [Kacser & Burns (1973) Symp. Soc. Exp. Biol. 27, 65-104; Heinrich & Rapoport (1974) Eur. J. Biochem. 42, 89-95]. Control of flux is almost exclusively located at the hexokinase- and phosphofructokinase-catalysed steps, whereas control of transition time is distributed more evenly between the enzymes of the system. The summation value of the Transition Time Control Coefficients is near to -1, suggesting the existence of another Summation Theorem besides that already stated for Flux Control Coefficients. Finally, we study the effect of an external stimulator of the system (fructose 2,6-bisphosphate) on the Control Coefficient profiles. The effect appears to be greater on the Transition Time Control Coefficient distribution than on the Flux Control Coefficients.
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PMID:Study of the flux and transition time control coefficient profiles in a metabolic system in vitro and the effect of an external stimulator. 276 3

Glucose 1,6-bisphosphate (G-1,6-P2) is a potent activator of phosphofructokinase (PFK) and an inhibitor of hexokinase in vitro. It has been suggested that increases in G-1,6-P2 are a main means by which PFK can achieve significant catalytic function in vivo despite falling pH and that increases in G-1,6-P2 will inhibit hexokinase in vivo. The purpose of the present study was to determine whether contraction-induced changes in flux through PFK and hexokinase are associated with changes in G-1,6-P2 in skeletal muscle. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal O2 uptake (VO2max) and to fatigue [4.8 +/- 0.6 (SE) min] at 100% VO2max. Biopsies were obtained from the quadriceps femoris muscle at rest and after each work load and analyzed for G-1,6-P2. G-1,6-P2 averaged 111 +/- 13 mumol/kg dry wt at rest and 121 +/- 16, 123 +/- 15, and 123 +/- 11 mumol/kg dry wt after the low-, moderate-, and high-intensity exercise bouts, respectively (P less than 0.05 for all means vs. rest). Flux through PFK was estimated to increase exponentially as the exercise intensity increased and muscle pH decreased at the higher work loads, whereas flux through hexokinase was estimated to increase during exercise at 40 and 75% VO2max but decrease sharply at 100% VO2max. These data demonstrate that flux through neither PFK nor hexokinase is mediated by changes in G-1,6-P2 in human skeletal muscle during short-term dynamic exercise.
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PMID:Carbohydrate metabolism in human skeletal muscle during exercise is not regulated by G-1,6-P2. 296 83

Yeast strains bearing a deficiency in trehalose-6-phosphate synthase activity are unable to accumulate trehalose on any carbon source unless they contain one of the MAL genes. If the gene is inducible then synthesis of trehalose occurs specifically during growth on maltose: when the MAL gene is constitutive then trehalose accumulation can also be seen when cells are grown on glucose. Different systems for trehalose synthesis were suggested: one of them would require the UDPG-linked trehalose synthase whereas the second would utilize an alternative pathway. We proposed a mechanism by which the gene-product of a MAL gene would serve as a common positive regulator for the expression of the genes coding for maltose permease, alpha-glucosidase and some component of the trehalose accumulation system. In order to elucidate this novel pathway a strain lacking UDPG-linked trehalose synthase activity and harboring a defect in maltose uptake was constructed. Excessive maltose uptake resulted in accumulation of intracellular maltose, and twice as much trehalose as in a control strain. Partial inhibition of hexokinase by xylose affected the ratio between internal maltose and trehalose and significantly reduced glycogen synthesis. Sodium fluoride also blocked glycogen synthesis but allowed for trehalose accumulation. Moreover, a mutant which lacks hexokinase I and II was unable to accumulate trehalose when grown on glucose in spite of the presence of a constitutive MAL2 gene. These results suggest that trehalose synthesis would require G-6-P formation derived from maltose. Such a deviation would allow for slowing down the glycolytic flux which, in turn, would favour efficient maltose utilization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Further evidence for the alternative pathway of trehalose synthesis linked to maltose utilization in Saccharomyces. 344 33

A method for determining Control Coefficients is proposed for systems studied in vitro and applied to a model pathway. Rat liver extract, which converts glucose into glycerol 3-phosphate, was used with the addition to the incubation mixture of fructose-bisphosphate aldolase, triose-phosphate isomerase and glycerol-3-phosphate dehydrogenase as 'auxiliary' enzymes, which leaves all the control on the first three enzymes. The flux of the metabolic pathway was recorded by assaying NADH decay. Flux Control Coefficients (CJE) of hexokinase, glucose-6-phosphate isomerase and phosphofructokinase were calculated by titration of the system with increasing quantities of extraneous enzymes. It is shown that the summation property is fulfilled. The applicability of this procedure to study the control in any metabolic pathway is discussed. Possible relevance of the method to conditions in vivo and its limitations are considered.
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PMID:Kinetics of metabolic pathways. A system in vitro to study the control of flux. 370 39

The conversion of glucose to lactate via the Embden-Meyerhof pathway yields a maximum of 2 mol of ATP per mol of glucose degraded with lesser amounts of ATP obtained if metabolic intermediates are removed for biosynthesis or if substrate cycling occurs during carbohydrate degradation. Bull sperm are an ideal test system for a quantitative estimate of ATP yield because they contain enzymes necessary for potential substrate cycling and do not carry out significant biosynthesis. Experiments utilized specifically labeled glucose and fructose to test for substrate cycling between glucose in equilibrium glucose-6-PO4, fructose in equilibrium fructose-6-PO4, and fructose-6-PO4 in equilibrium bisphosphate. Flux through the pathway (low = less than or equal to 0.05; moderate = 0.1; high = greater than 0.5 mol of carbohydrate consumed per h/10(8) cells) was altered by changing incubation temperature and/or by adding metabolic effectors. The data (in situ rates of kinases and phosphatases and metabolite crossover plots) obtained under these conditions were used to establish if the generally accepted regulatory enzymes (hexokinase and phosphofructokinase) approach the overall flux through the glycolytic pathway, i.e. that of a classical kinetically limiting rate-determining step. In summary: (a) At low flux, the rates of phosphorylation greatly exceeded overall flux. This resulted in extensive substrate cycling at all points and a net ATP yield of less than or equal to 0 mol/mol of glucose initially phosphorylated. (b) At moderate flux, rate of hexokinase approached that of overall flux through the glycolytic pathway but "excessive" phosphofructokinase activity led to substrate cycling between fructose-6-PO4 and fructose 1,6-bisphosphate and resulted in a low net ATP yield (0-0.6 mol/mol of glucose). (c) At high flux, rates of phosphofructokinase and hexokinase approached that of the overall flux. Minimal substrate cycling occurred between fructose-6-PO4 and fructose 1,6-bisphosphate, and the net ATP yield approached 1.8 mol/mol of glucose. These experiments established that the theoretical stoichiometric ATP yield of the pathway was rarely achieved during these incubations because of extensive substrate cycling. Indeed, for cauda epididymal bull sperm isolated and incubated in vitro, the glycolytic pathway serves to generate lactate, an intermediate product that is further metabolized in the mitochondria to yield the ATP that is associated with degradation of exogenous carbohydrate.
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PMID:The effect of substrate cycling on the ATP yield of sperm glycolysis. 686 9

Glucose and glutamine metabolism in several cultured mammalian cell lines (BHK, CHO, and hybridoma cell lines) were investigated by correlating specific utilization and formation rates with specific maximum activities of regulatory enzymes involved in glycolysis and glutaminolysis. Results were compared with data from two insect cell lines and primary liver cells. Flux distribution was measured in a representative mammalian (BHK) and an insect (Spodoptera frugiperda) cell line using radioactive substrates. A high degree of similarity in many aspects of glucose and glutamine metabolism was observed among the cultured mammalian cell lines examined. Specific glucose utilization rates were always close to specific hexokinase activities, indicating that formation of glucose-6-phosphate from glucose (catalyzed by hexokinase) is the rate limiting step of glycolysis. No activity of the key enzymes connecting glycolysis with the tricarboxylic acid cycle, such as pyruvate dehydrogenase, pyruvate carboxylase, and phosphoenolpyruvate carboxykinase, could be detected. Flux distribution in BHK cells showed glycolytic rates very similar to lactate formation rates. No glucose- or pyruvate-derived carbon entered the tricarboxylic acid cycle, indicating that glucose is mainly metabolized via glycolysis and lactate formation. About 8% of utilized glucose was metabolized via the pentose phosphate shunt, while 20 to 30% of utilized glucose followed pathways other than glycolysis, the tricarboxylic acid cycle, or the pentose phosphate shunt. About 18% of utilized glutamine was oxidized, consistent with the notion that glutamine is the major energy source for mammalian cell lines. Mammalian cells cultured in serum-free low-protein medium showed higher utilization rates, flux rates, and enzyme activities than the same cells cultured in serum-supplemented medium. Insect cells oxidized glucose and pyruvate in addition to glutamine. Furthermore, insect cells produced little or no lactate and were able to channel glycolytic intermediates into the tricarboxylic acid cycle. Metabolic profiles of the type presented here for a variety of cell lines may eventually enable one to interfere with the metabolic patterns of cells relevant to biotechnology, with the hope of improving growth rate and/or productivity.
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PMID:Comparative analysis of glucose and glutamine metabolism in transformed mammalian cell lines, insect and primary liver cells. 855 65

The rules that govern the relationships between enzymatic flux capacities (Vmax) and maximum physiological flux rates (v) at enzyme-catalyzed steps in pathways are poorly understood. We relate in vitro Vmax values with in vivo flux rates for glycogen phosphorylase, hexokinase, and phosphofructokinase, enzymes catalyzing nonequilibrium reactions, from a variety of muscle types in fishes, insects, birds, and mammals. Flux capacities are in large excess over physiological flux rates in low-flux muscles, resulting in low fractional velocities (%Vmax = v/Vmax x 100) in vivo. In high-flux muscles, close matches between flux capacities and flux rates (resulting in fractional velocities approaching 100% in vivo) are observed. These empirical observations are reconciled with current concepts concerning enzyme function and regulation. We suggest that in high-flux muscles, close matches between enzymatic flux capacities and metabolic flux rates (i.e., the lack of excess capacities) may result from space constraints in the sarcoplasm.
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PMID:Relationships between enzymatic flux capacities and metabolic flux rates: nonequilibrium reactions in muscle glycolysis. 919 92


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