Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The positively charged photosensitizer toluidine blue (TB) can induce loss of clonogenicity in Kluyveromyces marxianus. Previous studies have revealed that, as a consequence of the localization of this dye at the cell surface, photodynamic action results in extensive damage at the level of the plasma membrane. In this paper, a study is reported on the effect of photodynamic treatment with TB on intracellular enzymes. It is shown that treatment with TB and light resulted in the inhibition of alcohol dehydrogenase, cytochrome c oxidase, glyceraldehyde-3-phosphate dehydrogenase and hexokinase. Photodynamic treatment also lowered the ATP levels. The ATP levels could be partially restored in the presence of glucose but not with ethanol. Toluidine blue binding experiments revealed that photodynamic treatment caused a rapid increase in the amount of cell-associated dye. Moreover, it also appeared that this treatment decreased the binding of TB to the cell surface. It is concluded that TB enters the cell during the first minutes of illumination, whereafter intracellular enzymes are inactivated. The data indicate that photodynamic damage of intracellular sites contributes to the loss of viability.
 ...
PMID:Intracellular damage in yeast cells caused by photodynamic treatment with toluidine blue. 789 97

Glycolytic oscillations can be induced by adding glucose to starved Saccharomyces cerevisiae cells and, after a steady state has been established, cyanide. Transient oscillations or limit-cycle oscillations can be induced depending on the growth phase in which the cells are harvested. To find what causes these differences in the dynamic behaviour, we analyzed glycolytic enzyme activities at different growth phases. The hexokinase activity increased by a factor of three after growth substrate transition from glucose to ethanol; the other measured activities remained constant. Cyanide was found not only to block respiration, but also to trap acetaldehyde. Both cyanide actions appear necessary for the occurrence of sustained glycolytic oscillations.
 ...
PMID:Yeast cells with a specific cellular make-up and an environment that removes acetaldehyde are prone to sustained glycolytic oscillations. 813 43

We cloned and sequenced the pyruvate decarboxylase (PDC; EC 4.1.1.1) structural gene KIPDCA in the yeast Kluyveromyces lactis and found it to be allelic to the previously isolated rag6 mutation. The putative amino acid sequence of the KIPdcAp appeared to be highly homologous to those of the yeast Pdc proteins identified so far. The disruption of KIPDCA indicated that it is the only PDC structural gene in K. lactis, as evidenced by the lack of PDC activity and ethanol production in the pdcA delta strains and by the absence of growth on glucose in the presence of respiratory inhibitors. It was observed that expression of the KIPDCA gene is induced by glucose at the transcriptional level. Transcription of the gene was reduced in the rag1, rag2, rag5 and rag8 mutants, which are defective for the low-affinity glucose permease, phosphoglucose isomerase, hexokinase, and a positive regulator of RAG1 expression, respectively.
 ...
PMID:The 'petite-negative' yeast Kluyveromyces lactis has a single gene expressing pyruvate decarboxylase activity. 882 34

The HXK2 gene is required for a variety of regulatory effects leading to an adaptation for fermentative metabolism in Saccharomyces cerevisiae. However, the molecular basis of the specific role of Hxk2p in these effects is still unclear. One important feature in order to understand the physiological function of hexokinase PH is that it is a phosphoprotein, since protein phosphorylation is essential in most metabolic signal transductions in eukaryotic cells. Here we show that Hxk2p exists in vivo in a dimeric-monomeric equilibrium which is affected by phosphorylation. Only the monomeric form appears phosphorylated, whereas the dimer does not. The reversible phosphorylation of Hxk2p is carbon source dependent, being more extensive on poor carbon sources such as galactose, raffinose, and ethanol. In vivo dephosphorylation of Hxk2p is promoted after addition of glucose. This effect is absent in glucose repression mutants cat80/grr1, hex2/reg1, and cid1/glc7. Treatment of a glucose crude extract from cid1-226 (glc7-T152K) mutant cells with lambda-phosphatase drastically reduces the presence of phosphoprotein, suggesting that CID1/GLC7 phosphatase together with its regulatory HEX2/REG1 subunit are involved in the dephosphorylation of the Hxk2p monomer. An HXK2 mutation encoding a serine-to-alanine change at position 15 [HXK2 (S15A)] was to clarify the in vivo function of the phosphorylation of hexokinase PII. In this mutant, where the Hxk2 protein is unable to undergo phosphorylation, the cells could not provide glucose repression of invertase. Glucose induction of HXT gene expression is also affected in cells expressing the mutated enzyme. Although we cannot rule out a defect in the metabolic state of the cell as the origin of these phenomena, our results suggest that the phosphorylation of hexokinase is essential in vivo for glucose signal transduction.
 ...
PMID:Carbon source-dependent phosphorylation of hexokinase PII and its role in the glucose-signaling response in yeast. 956 13

In the yeast Saccharomyces cerevisiae a novel control exerted by TPS1 (= GGS1 = FDP1 = BYP1 = CIF1 = GLC6 = TSS1)-encoded trehalose-6-phosphate synthase, is essential for restriction of glucose influx into glycolysis apparently by inhibiting hexokinase activity in vivo. We show that up to 50-fold overexpression of hexokinase does not noticeably affect growth on glucose or fructose in wild-type cells. However, it causes higher levels of glucose-6-phosphate, fructose-6-phosphate and also faster accumulation of fructose-1,6-bisphosphate during the initiation of fermentation. The levels of ATP and Pi correlated inversely with the higher sugar phosphate levels. In the first minutes after glucose addition, the metabolite pattern observed was intermediate between those of the tps1 delta mutant and the wild-type strain. Apparently, during the start-up of fermentation hexokinase is more rate-limiting in the first section of glycolysis than phosphofructokinase. We have developed a method to measure the free intracellular glucose level which is based on the simultaneous addition of D-glucose and an equal concentration of radiolabelled L-glucose. Since the latter is not transported, the free intracellular glucose level can be calculated as the difference between the total D-glucose measured (intracellular + periplasmic/extracellular) and the total L-glucose measured (periplasmic/extracellular). The intracellular glucose level rose in 5 min after addition of 100 mM-glucose to 0.5-2 mM in the wild-type strain, +/- 10 mM in a hxk1 delta hxk2 delta glk1 delta and 2-3 mM in a tps1 delta strain. In the strains overexpressing hexokinase PII the level of free intracellular glucose was not reduced. Overexpression of hexokinase PII never produced a strong effect on the rate of ethanol production and glucose consumption. Our results show that overexpression of hexokinase does not cause the same phenotype as deletion of Tps1. However, it mimics it transiently during the initiation of fermentation. Afterwards, the Tps1-dependent control system is apparently able to restrict properly up to 50-fold higher hexokinase activity.
 ...
PMID:During the initiation of fermentation overexpression of hexokinase PII in yeast transiently causes a similar deregulation of glycolysis as deletion of Tps1. 958 Feb 51

The steady-state levels of messenger RNA (mRNA) of the glucose transporters 1 and 3 and the glycolytic enzymes hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate dehydrogenase were measured in up to seven brain regions of the rat in a recently developed animal model of 'behavioral dependence' on ethanol. Irreversible behavioral dependence, including loss of control, was induced by offering the rats the choice between ethanol and water over a 9-month period (Group A). This group was compared with a group given the choice between ethanol and water for only 2 months (not yet behaviorally dependent, Group B), a group forced to consume ethanol as sole fluid over a 9-month period (not behaviorally dependent, Group C) and ethanol-naive control rats. All groups were sacrificed 1 month after ethanol withdrawal. The mRNA concentrations of both neuronal glucose transporter 3 and the key glycolytic enzymes phosphofructokinase and pyruvate dehydrogenase were significantly reduced in the hippocampi of the rats behaviorally dependent on ethanol (Group A). No significant changes were seen in any of the remaining brain regions (e.g., cortical areas, limbic forebrain, amygdala, midbrain) in Group A, or in any brain area at all in Groups B and C. The results show that chronic consumption of ethanol in a free-choice situation may impair neuronal glucose uptake and glycolytic flux. This effect is manifested exclusively in the hippocampus and is specifically related to the development of behavioral dependence, since it was not found after forced administration of large amounts of ethanol (Group C).
 ...
PMID:Gene expression of glucose transporters and glycolytic enzymes in the CNS of rats behaviorally dependent on ethanol. 1003 12

In glucose-limited continuous cultures, a Crabtree positive yeast such as Saccharomyces cerevisiae displays respiratory metabolism at low dilution rates (D) and respiro-fermentative metabolism at high D. We have studied the onset of ethanol production and cell cycle behavior in glucose-limited chemostat cultures of the wild type S. cerevisiae strain CEN.PK122 (WT) and isogenic mutants, snf1 (cat1) and snf4 (cat3) defective in proteins involved in catabolite derepression and the mutant in glucose repression mig1 (cat4). The triggering of fermentative metabolism was dependent upon catabolite repression properties of yeast and was coincident with a significant decrease of G1 length. WT cells of the strain CEN.PK122 displayed respiratory metabolism up to a D of 0.2 h-1 and exhibited longer G1 lengths than the snf1 and snf4 mutants that started fermenting after a D of 0.1 and 0.15 h-1, respectively. The catabolite derepression mutant snf4 showed a significant decrease in the duration of G1 with respect to the WT. An increase of 300% to 400% in the expression of CDC28 (CDC28-lacZ) with a noticeable shortening in G1 to values lower than approximately 150 min, was detected in the transformed wild type CEN.SC13-9B in glucose-limited chemostat cultures. The expression of CDC28-lacZ was analyzed in the wild type and isogenic mutant strains growing at maximal rate on glucose or in the presence of ethanol or glycerol. Two- to three-fold lower expression of the CDC28-lacZ fusion gene was detected in the snf1 or snf4 disruptants with respect to the WT and mig1 strains in the presence of all carbon sources. This effect was further shown to be growth rate-dependent exhibiting apparently, a threshold effect in the expression of the fusion gene with respect to the length of G1, similar to that shown in chemostat cultures. At the onset of fermentation, the control of the glycolytic flux was highly distributed between the uptake, hexokinase, and phosphofructokinase steps. Particularly interesting was the fact that the snf1 mutant exhibited the lowest fluxes of ethanol production, the highest of respiration and correspondingly, the branch to the tricarboxylic acid cycle was significantly rate-controling of glycolysis.
 ...
PMID:Catabolite repression mutants of Saccharomyces cerevisiae show altered fermentative metabolism as well as cell cycle behavior in glucose-limited chemostat cultures. 1009 31

The effects of the ethanol extract of the root of Plumbago zeylanica on key enzymes of glycolysis and other biochemical parameters were studied in the rat. The results show that thigh muscle hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase activities were significantly reduced (p < 0.05) by 12.07%, 51.02%, 24.32% and 25.16% respectively in rats treated with the ethanol extract of Plumbago zeylanica when compared with the controls. Serum pyruvate and lactate were significantly lowered in the experimental rats by 23.64% and 46.29%, respectively. The difference between the supernatant protein means was not statistically different (p > 0.05) suggesting the preservation of protein synthesis in the muscle of the extract-treated rats. The reduction in the activities of the key enzymes of glycolysis and its end-products suggests a reduction in flux across the glycolytic pathway in the extract-treated rats. This may be a result of impaired delivery to, and utilization of, glucose by the peripheral tissue, thus substantiating the reported hyperglycaemia in the extract-treated rats.
 ...
PMID:An investigation into the biochemical basis of the observed hyperglycaemia in rats treated with ethanol root extract of plumbago zeylanica. 1040 46

In the yeast Saccharomyces cerevisiae, TPS1-encoded trehalose-6-phosphate synthase (TPS) exerts an essential control on the influx of glucose into glycolysis, presumably by restricting hexokinase activity. Deletion of TPS1 results in severe hyperaccumulation of sugar phosphates and near absence of ethanol formation. To investigate whether trehalose 6-phosphate (Tre6P) is the sole mediator of hexokinase inhibition, we have reconstituted ethanolic fermentation from glucose in permeabilized spheroplasts of the wild-type, tps1Delta and tps2Delta (Tre6P phosphatase) strains. For the tps1Delta strain, ethanol production was significantly lower and was associated with hyperaccumulation of Glu6P and Fru6P. A tps2Delta strain shows reduced accumulation of Glu6P and Fru6P both in intact cells and in permeabilized spheroplasts. These results are not consistent with Tre6P being the sole mediator of hexokinase inhibition. Reconstitution of ethanolic fermentation in permeabilized spheroplasts with glycolytic intermediates indicates additional target site(s) for the Tps1 control. Addition of Tre6P partially shifts the ethanol production rate and the metabolite pattern in permeabilized tps1Delta spheroplasts to those of the wild-type strain, but only with glucose as substrate. This is observed at a very high ratio of glucose to Tre6P. Inhibition of hexokinase activity by Tre6P is less efficiently counteracted by glucose in permeabilized spheroplasts compared to cell extracts, and this effect is largely abolished by deletion of TPS2 but not TPS1. In permeabilized spheroplasts, hexokinase activity is significantly lower in a tps2Delta strain compared to a wild-type strain and this difference is strongly reduced by additional deletion of TPS1. These results indicate that Tps1-mediated protein-protein interactions are important for control of glucose influx into yeast glycolysis, that Tre6P inhibition of hexokinase might not be competitive with respect to glucose in vivo and that also Tps2 appears to play a role in the control of hexokinase activity.
 ...
PMID:Reconstitution of ethanolic fermentation in permeabilized spheroplasts of wild-type and trehalose-6-phosphate synthase mutants of the yeast Saccharomyces cerevisiae. 1088 Sep 82

The Indian traditional system of medicine prescribed traditional plant therapies. Two such plants, i.e. Momordica charantia (MC) and Mucuna pruriens (MP), earlier shown to reduce hyperglycaemia, were assessed for their anti hyperglycaemic effect on varying degrees of hyperglycaemia and diabetic complications. Alcohol and aqueous extracts of MC (50, 100 and 200 mg/kg/day) and only an alcohol extract of MP (100, 200 and 400 mg/kg/day) were evaluated in a pilot study (plasma glucose >180 mg/dL, 21 days), a chronic study in alloxanized rats (plasma glucose >280mg/dL, 120 days) and streptozotocin (STZ) mice (plasma glucose >400 mg/dL, 60 days). In the pilot study, the maximum antihyperglycaemic effect occurred with an aqueous extract of MC at week 3 and an alcohol extract of MP at week 6 at a dose of 200 mg/kg/day. In chronic alloxanized rats, the selected dose of MC led to a significant fall of 64.33%, 66.96%, 69.7% and 70.53% in plasma glucose levels at 1, 2, 3 and 4 months, respectively. MP showed a decrease of 40.71%, 45.63%, 50.33% and 51.01% at the same time period. In chronic STZ diabetic mice, MC led to a mean reduction of 15.37%, 18.68% and 22.86% in plasma glucose levels on days 40, 50 and 60 of sampling while MP had no significant effect. The alteration in hepatic and skeletal muscle glycogen content and hepatic glucokinase, hexokinase, glucose-6-phosphate and phosphofructokinase levels in diabetic mice were partially restored by MC but not by MP. The mechanism of action of MC and MP is discussed.
 ...
PMID:The effect of Momordica charantia and Mucuna pruriens in experimental diabetes and their effect on key metabolic enzymes involved in carbohydrate metabolism. 1216 68


<< Previous 1 2 3 4 5 6 7 8 Next >>