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 effect of hypoxia and post-hypoxic recovery were studied in gastrocnemius muscle of young-adult and mature beagle dogs. Furthermore, the possible interference of pharmacological treatment with nicergoline was evaluated in these conditions. Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose 6-phosphate, pyruvate, lactate), Kreb's cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate) and related free amino acids (glutamate, alanine), ammonium ion, energy store and mediators (ATP, ADP, AMP and creatine phosphate), and the energy charge potential were evaluated. Furthermore, in the crude extract and/or mitochondrial fraction of another portion of the same gastrocnemius muscle the maximum rate (Vmax) of some muscular enzymes related to the anaerobic glycolytic pathway (hexokinase, lactate dehydrogenase), the Kreb's cycle (citrate synthase, malate dehydrogenase), the aminoacid pool related to the Krebs' cycle (glutamate dehydrogenase and aspartate aminotransferase), the electron transfer chain (cytochrome oxidase) and NAD+/NADH exchanges (total NADH cytochrome c reductase) was evaluated. Some glycolytic metabolites and Krebs' cycle intermediates were modified by acute hypoxia, while free amino acids and energy mediators remained practically unchanged. The pharmacological treatment maintained the glucose and succinate muscular concentrations within the normal range, during hypoxia. The behaviour of muscular metabolites during hypoxia and/or post-hypoxic recovery is an age-related event. In fact, only in young-adult animals did the altered values return to normal in post-hypoxic recovery. In the present experimental conditions, only minor changes were observed as far as muscular enzyme activities are concerned. In any case, some enzyme activities tested showed different Vmax in young-adult dogs in comparison with mature ones.
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PMID:Effect of hypoxia, aging and pharmacological treatment on muscular metabolites and enzyme activities. 322 9

The erythrocyte can phosphorylate a variety of hexoses. Since it can consume mannose and glucose equivalently in the hereditary deficiencies of hexokinase and phosphoglucose isomerase and since erythrocyte defense against oxidants is impaired in a variety of hereditary hemolytic anemias, we tested the hypothesis that mannose may be a significant alternative to glucose as a fuel for this defense system. Unexpectedly, mannose inhibited defense against oxidants as manifested by increased Heinz body formation when both normal and high-reticulocyte erythrocytes were incubated with acetylphenylhydrazine (APH). Using APH as the oxidant, mannose-incubated erythrocytes had decreased reduced glutathione stability and impaired hexose oxidation by the pentose shunt compared to glucose-incubated erythrocytes. After incubation with mannose and APH, normal erythrocytes showed a decrease in ATP content. Approximately 25% of the consumed mannose accumulated in the erythrocytes as mannose 6-phosphate. Erythrocytes incubated with mannose and APH displayed a significant loss of redox potential as manifested by decreased NADH/(NADH + NAD+) and NADPH/(NADPH + NADP+) ratios. Since phosphomannose isomerase is the rate-limiting step for mannose metabolism, our results suggest that mannose impairs erythrocyte defense against oxidants by causing ATP depletion and by impairing the regeneration of reduced pyridine nucleotides by the Embden-Meyerhof and pentose phosphate pathways.
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PMID:Inhibitory effect of mannose on erythrocyte defense against oxidants. 333 78

In basic solutions, pyruvate enolizes and reacts (through its 3-carbon) with the 4-carbon of the nicotinamide ring of NAD+, yielding an NAD-pyruvate adduct in which the nicotinamide ring is in the reduced form. This adduct is a strong inhibitor of lactate dehydrogenase, presumably because it binds simultaneously to the NADH and pyruvate sites. The potency of the inhibition, however, is muted by the adduct's tendency to cyclize to a lactam. We prepared solutions of the pyruvate adduct of NAD+ and of NAD+ analogues in which the -C(O)NH2 of NAD+ was replaced with -C(S)NH2, -C(O)CH3, and -C(O)H. Of the four, only the last analogue, 3-[4-(reduced 3-pyridine aldehyde-adenine dinucleotide)]-pyruvate (RAP) cannot cyclize and it was found to be the most potent inhibitor of beef heart and rat brain lactate dehydrogenases. The inhibitor binds very tightly to the NADH site (Ki approximately 1 nM for the A form). Even at high concentrations (20 microM), RAP had little or no effect on rat brain glyceraldehyde-3-phosphate, pyruvate, alpha-ketoglutarate, isocitrate, soluble and mitochondrial malate, and glutamate dehydrogenases. The glycolytic enzymes, hexokinase and phosphofructokinase, were similarly unaffected. RAP strongly inhibited lactate production from glucose in rat brain extracts but was less effective in inhibiting lactate production from glucose in synaptosomes.
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PMID:Inhibition of lactate production in rat brain extracts and synaptosomes by 3-[4-(reduced 3-pyridine aldehyde-adenine dinucleotide)]-pyruvate. 357 4

In the process of defining the recruitment of fuel and pathway selection in rainbow trout fast-twitch white skeletal muscle, it was clear that the near-maximal myosin adenosinetriphosphatase activity during a 10-s sprint was supported solely by phosphocreatine hydrolysis. A conservative estimate of the ATP turnover was 188 mumol X g wet wt-1 X min-1. It was not until the rate and force of contraction decreased that the relative contribution of anaerobic glycogenolysis became increasingly important. Over a 10-min period of burst swimming at approximately 120% of maximum aerobic steady-state swimming velocity of trout determined in a Brett-type swim tunnel, fatigue was associated with the near-depletion of glycogen in white muscle. The ATP turnover supported by anaerobic glycogenolysis was 78 mumol X g wet wt-1 X min-1. The glycolytic pathway appeared functional at this time with control sites being identified at hexokinase and phosphofructokinase (PFK-1). PFK-1 did not appear to be inhibited by low muscle pH (pH 6.66). In another exercise protocol lasting 30 min, complete exhaustion was related to glycogen depletion. The sum of all glycolytic intermediates from glucose 6-phosphate to pyruvate at exhaustion decreased by a dramatic 80% compared with the 25% decrease for the 10-min fatigue swimming protocol. This large depletion of glycolytic intermediates was accompanied by an 80% fall in ATP, a 70-80% reduction in the ATP/ADP and phosphorylation potential, and a 2.5-fold increase in the NAD/NADH. Associated with these changes was a marked displacement of the phosphoglycerate kinase (PGK), and the combined glyceraldehyde-3-phosphate dehydrogenase-PGK reactions from thermodynamic equilibrium. As a general conclusion, fatigue and exhaustion should be viewed as a multicomponent biochemical process in response to low glycogen and not leveled at one particular step of the glycolytic pathway.
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PMID:Regulation of anaerobic ATP-generating pathways in trout fast-twitch skeletal muscle. 360 83

It is shown in experiments on rats that the early postischemic period after 1- and 1.5-hour ischemia of kidneys is characterized by a decrease in the damage of the glycolytic system site which induces glucose-6-phosphate transformation into lactate and by an increase in the inhibition intensity of the initial hexokinase reaction of glycolysis. In the postischemic period after more prolonged (2-, 3-hour) ischemia the damage of the glycolytic system develops also at the site of glucose-6-phosphate transformation into lactate. Administration either of the nucleotide complex (NAD and AMP) or calmodulin inhibitors (aminazine and zinc sulphate) to rats prior to two-hour occlusion of kidneys vessels promotes a decrease in the inhibition of the glycolytic system activity in the postischemic period. At the same time the separate and combined application of zinc sulphate and triftazin (the most intensive calmodulin inhibitor) is not efficient. The positive effect of NAD, AMP and aminazine on the state of the glycolytic kidney system in the postischemic period correlates with the improvement of the blood microcirculation processes in them.
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PMID:[Glycolysis in the rat kidney shortly after ischemia and administration of calmodulin inhibitors, AMP and NAD]. 379 79

M. Kuwajima, C. B. Newgard, D. W. Foster, and J. D. McGarry (1986, J. Biol. Chem. 261, 8849-8853) have concluded that the reason postprandial hepatic glycogenesis occurs primarily from gluconeogenic precursors rather than glucose is because glucokinase activity is insufficient to support the observed rates of glycogen synthesis. F. L. Alvares and R. C. Nordlie (1977, J. Biol. Chem. 252, 8404-8414) have concluded that the combined activities of glucokinase and hexokinase are less than the apparent rates of hepatic glucose uptake. We have identified several factors in the assays used in these studies which lead to substantial underestimations of glucokinase activity. Glucokinase was assayed either by allowing glucose 6-phosphate to accumulate over 10 min (discontinuous assay) or by coupling the formation of glucose 6-phosphate with its oxidation by Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase and NAD (continuous assay). Accurate determinations of glucokinase at 37 degrees C with subsaturating glucose require both 100 mM KCl and 2.5 mM dithioerythritol in the assay medium; 2-mercaptoethanol will not substitute for dithioerythritol. When both KCl and dithioerythritol are absent (Kuwajima et al.) glucokinase activity is underestimated by 3- to 5-fold. The discontinuous assay as used previously (Alvares and Nordlie) underestimates glucokinase activity in crude extracts by 2- to 2.5-fold, due in part to the hydrolysis of glucose 6-phosphate and its transformation to other hexose monophosphates. Under optimized conditions at 37 degrees C both assays yield similar results in extracts from fed rats, i.e., 2-3 and 4-5 units/g liver at 10 and 100 mM glucose, respectively. Some implications of the finding that total hepatic glucose phosphorylating capacity at physiological concentrations significantly exceeds the observed rates of postprandial glycogen synthesis are discussed.
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PMID:Factors underlying significant underestimations of glucokinase activity in crude liver extracts: physiological implications of higher cellular activity. 381 60

Lonidamine is a potent inhibitor of spermatogenesis and a hyperthermic sensitizer. The principal established locus of biochemical action of lonidamine is a selective inhibitory effect of the energy metabolism either in NAD-linked reactions in germ cell mitochondria, as well as the glycolytic metabolism of a variety of tumor cell lines by means of inhibition of mitochondrially bound hexokinase. We carried out in vivo tumor experiments to determine whether lonidamine when combined with radiation could potentiate the cytotoxic effects of radiation on two murine tumors. The combined effects of single acute lonidamine (100 mg/kg) and single dose X-irradiation were evaluated on the transplanted methylcholanthrene-induced fibrosarcoma in BALB/c mice and on the radiation-induced fibrosarcoma in C3H/He mice. The radiosensitizing effect by lonidamine was maximal when lonidamine was administered immediately prior to or after X-irradiation. The dose modifying factor of lonidamine is estimated to be 1.36 for methylcholanthrene-induced fibrosarcoma tumors and 1.25 for radiation-induced fibrosarcoma tumors. There was no disproportionately enhanced skin reaction following the combined treatments. The present results of the potentiating effects of radiation may be attributed, in part, to the findings of cell culture studies that lonidamine is a potent inhibitor of repair of potentially lethal damage.
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PMID:Potentiation of radiation effects on two murine tumors by lonidamine. 394 89

Metabolic activity of erythrocytes was studied in healthy pregnant women. The second half of the normal pregnancy was characterized by an increase in activity of hexokinase, in content of 2,3-DPG, ADP, by a distinct decrease in ATP, NAD and the ratio ATP/ADP as well as by unaltered ratios NAD/NADH and lactate/pyruvate.
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PMID:[Glycolytic enzyme activity and levels of glycolysis metabolites in erythrocytes in physiological pregnancy]. 400 52

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.
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PMID:Differences in some of the metabolic properties of mitochondria isolated from cerebral cortex and olfactory bulb of the rat. 404 57

1. Enzymic evidence supporting the operation of the Entner-Doudoroff pathway in the anaerobic conversion of glucose into ethanol and carbon dioxide by Zymomonas mobilis is presented. 2. Cell extracts catalysed the formation of equimolar amounts of pyruvate and glyceraldehyde 3-phosphate from 6-phosphogluconate. Evidence that 3-deoxy-2-oxo-6-phosphogluconate is an intermediate in this conversion was obtained. 3. Cell extracts of the organism contained the following enzymes: glucose 6-phosphate dehydrogenase (active with NAD and NADP), ethanol dehydrogenase (active with NAD), glyceraldehyde 3-phosphate dehydrogenase (active with NAD), hexokinase, gluconokinase, glucose dehydrogenase and pyruvate decarboxylase. Extracts also catalysed the overall conversion of glycerate 3-phosphate into pyruvate in the presence of ADP. 4. Gluconate dehydrogenase, fructose 1,6-diphosphate aldolase and NAD-NADP transhydrogenase were not detected. 5. It is suggested that NAD is the physiological electron carrier in the balanced oxidation-reduction involved in ethanol formation.
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PMID:The route of ethanol formation in Zymomonas mobilis. 428 42


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