Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Fructosediphosphates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1989

Effects of long-term feeding of high-protein or high-fat diets on the response to exercise in the rat.

The aim of this work was to find by which mechanisms an increased availability of plasma free fatty acids (FFA) reduced carbohydrate utilization during exercise. Rats were fed high-protein medium-chain triglycerides (MCT), high-protein long-chain triglycerides (LCT), carbohydrate (CHO) or high-protein low-fat (HP) diets for 5 weeks, and liver and muscle glycogen, gluconeogenesis and FFA oxidation were studied in rested and trained runner rats. In the rested state the hepatic glycogen store was decreased by fat and protein feeding, whereas soleus muscle glycogen concentration was only affected by high-protein diets. The percentage decrease in liver and muscle glycogen stores, after running, was similar in fat-fed, high-protein and CHO-fed rats. The fact that plasma glucose did not drastically change during exercise could be explained by a stimulation of hepatic gluconeogenesis: the activity of phosphoenolpyruvate carboxykinase (PEPCK) and liver phosphoenolpyruvate (PEP) concentration increased as well as cyclic adenosine monophosphate (AMPc) while liver fructose 2,6-bisphosphate decreased and plasma FFA rose. In contrast, the stimulation of gluconeogenesis in rested HP-, MCT- and LCT-fed rats appears to be independent of cyclic AMP.

Animals↗
PubMed1996

Fructose 2,6-bisphosphate metabolism during megakaryocytic differentiation of K562 and MEG-01 cells.

Fructose 2,6-bisphosphate (Fru-2, 6-P2) represents the most powerful activator of 6-phosphofructo-1-kinase, rate-limiting enzyme of glycolysis. Fru-2,6-P2 content is tightly regulated and appears to be under the control of different hormones and growth factors, acting either through covalent modification of isoenzymatic forms of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2/FBPase-2), the bifunctional enzyme responsible for the synthesis and the degradation of the compound, or through changes in transcription rate and/or in the expression of different isoforms of the enzyme. In the present study the metabolism of Fru-2,6-P2 was investigated during the differentiation toward megakaryocytes induced by phorbol 12-myristate 13-acetate (PMA) treatment of human leukemia K562 and MEG-01 cell lines. Fru-2,6-P2 content as well as PFK-2 activity were increased in a dose-dependent manner after 4 days of incubation with PMA. MEG-01 cells resulted more sensitive to the effect of the inducer, anyway in both cell types cytostatic concentrations of the phorbol ester were able to affect Fru-2,6-P2 metabolism. The effect of PMA was maximal at 4 days of incubation in both examined cell lines. Interestingly, the effect induced by the phorbol ester at 4 days was still appreciable subculturing K562 and MEG-01 cells for 3 days in the absence of the inducer and was associated with relevant changes in the molecular properties of PFK-2: namely increased Vmax and K(m). This latter finding suggests that the rise in Fru-2,6-P2 content during the differentiation process toward megakaryocytes might result from the expression of a novel PFK-2 isoform.

Carcinogens↗
PubMed1990

Protective effects of fructose-1,6-diphosphate on acute and chronic doxorubicin cardiotoxicity in rats.

The effects of fructose-1,6-diphosphate, an intermediate metabolite of glycolysis, on acute and chronic cardiotoxicity of doxorubicin were investigated in rats. In the acute study, urethane-anaesthetized Wistar female rats treated with 10 mg/kg i.v. doxorubicin developed a widening of the S alpha T segment, an impairment of +dP/dtmax, and tachycardia. Pretreatment with 375 and 750 mg/kg i.p. fructose-1,6-diphosphate prevented the S alpha T segment from widening, whereas only 750 mg/kg i.p. significantly attenuated the heart rate increase. Chronic cardiomyopathy was induced over a 6-week period by weekly doses of 3 mg/kg i.v. doxorubicin, being characterized in vivo by the progressive enlargement of the S alpha T segment and the occurrence of histological alterations and in vitro by a marked impairment of the inotropic response elicited by adrenaline in isolated hearts from treated rats. Concurrent treatment with 150 and 300 mg/kg i.p. fructose-1,6-diphosphate thrice a week for 6 weeks did not lessen the chronic heart damage, whereas 600 mg/kg given i.p. significantly reduced the widening of the S alpha T segment and the severity of histological damage in vivo, as well as significantly improving the contractile responses of hearts in vitro. These findings suggest that the administration of fructose-1,6-diphosphate plays a protective role in the acute and chronic cardiotoxicity of doxorubicin in the rat.

Acute Disease↗
PubMed1993

Urinary sugar phosphates and related organic acids in fructose-1,6-diphosphatase deficiency.

Two sisters with fructose-1,6-diphosphatase deficiency are reported. They presented with ketonuria, elevated plasma transaminase activity and severe metabolic acidosis during hypoglycaemic crises, which resembled Reye syndrome. Intravenous fructose tolerance tests provoked severe hypoglycaemia and metabolic acidosis. Fructose-1,6-diphosphatase activities in both peripheral leukocytes and cultured lymphocytes were below the limit of detection. Urinary organic acid analysis during crises revealed markedly increased excretion of lactate, ketone bodies, glycerol and glycerol-3-phosphate. We newly identified other glycolytic intermediates, glyceraldehyde, 3-phosphoglycerate and fructose-1,6-diphosphate, in the urine during hypoglycaemic attacks or after fructose tolerance tests. Identification of such compounds may be useful in the early diagnosis of this disease.

Female↗
PubMedDate not supplied

Exogenous fructose-1,6-bisphosphate is a metabolizable substrate for the isolated normoxic rat heart.

Isolated rat hearts were perfused by the recirculating Langendorff mode under normoxic conditions for 60 min. The Krebs-Ringer buffer was supplemented with 10 mM glucose + 12 IU/l insulin and either [U-14C]-fructose-1,6-bisphosphate (together with 5 mM cold fructose-1,6-bisphosphate) or [U-14C]-fructose (together with 5 mM cold fructose). At the end of perfusion, gaseous 14CO2, 14CO2 trapped in the perfusates, 14C-lactate output and tissue 14C-lactate were assayed in both groups of hearts. Analysis of high-energy compounds, glycogen, lactate, and pyruvate was also performed on the neutralized perchloric acid extracts of the freeze-clamped hearts. Data obtained from the 14C catabolites, originating from the metabolism of the radiolabeled substrates, indicated that the isolated normoxic rat heart metabolizes an 8.5 times higher amount of fructose-1,6-bisphosphate (7.07 mumoles/min/g d.w.) than of fructose (0.83 mumoles/min/g d.w.). CrP, CrP/Cr, glycogen, and total lactate in both tissue and perfusate were significantly higher in fructose-1,6-bisphosphate-perfused hearts. The overall indication is that fructose-1,6-bisphosphate can be taken up in its intact form by myocytes and successively metabolized to support their energy demand, and that its effects on myocardial performance and metabolism should be attributed to the molecule itself rather than to its eventual degradation products.

Animals↗
PubMed1993

Control of glycolytic enzyme binding: effect of changing enzyme substrate concentrations on in vivo enzyme distributions.

The effect of changing concentrations of glycolytic intermediates on the binding of phosphofructokinase, aldolase and pyruvate kinase to cellular particulate matter was investigated. Concentrations of glycolytic intermediates were altered by adding 2 mM iodoacetic acid (IAA) to an incubation medium containing tissues isolated from the channelled whelk Busycon canaliculatum. Iodoacetic acid inhibited glyceraldehyde 3-phosphate dehydrogenase activity causing a 100-400 fold increase in the concentration of fructose 1,6-bisphosphate as well as 3-20 fold increases in glucose 6-phosphate, fructose 6-phosphate, and dihydroxyacetone phosphate levels depending on the experimental protocol. Cellular pH values were not statistically different in the presence of IAA. Measurement of enzyme binding to particulate matter showed that the binding of phosphofructokinase, aldolase and pyruvate kinase was unaffected by iodoacetic acid under any experimental condition. These results show that changes in the tissue concentrations of enzyme substrates and products do not regulate enzyme binding to particulate matter in the cell.

Animals↗
PubMed1993

Regulation of brain 6-phosphofructo-1-kinase: effects of aging, fructose-2,6-bisphosphate, and regional subunit distribution.

Total 6-phosphofructo-1-kinase (PFK) activity, amounts of each type of PFK subunit, and levels of fructose-2,6-P2 in the cerebral cortex, midbrain, pons-medulla, and cerebellum of 3, 12, and 25 month rats were measured. Further, the role of fructose-2,6-P2 in the regulation of brain PFK activity was examined. A positive correlation was found to exist between the reported losses of glucose utilization as measured by 2-deoxy-D-glucose uptake and PFK activity in each region. That is, both parameters decreased to their lowest level by 12 months of age and remained decreased and fairly constant thereafter. Fructose-2,6-P2 levels did not appear to directly correlate with regional changes in glucose utilization. Also, region-specific and age-related alterations of the PFK subunits were found although these changes apparently did not correlate with decreased glucose utilization. Brain PFK is apparently saturated with fructose-2,6-P2 due to the high endogenous levels, and it contains a large proportion of the C-type subunit which dampens catalytic efficiency. Consequently, brain PFK could exist in a conformational state such that it can readily consume fructose-6-P rather than in an inhibited state requiring activation. This may explain, in part, the ability of brain to efficiently but conservatively utilize available glucose in energy production.

Aging↗
PubMed1993

Effects of iloprost, a PGI2 derivative, on ischemic myocardial energy and carbohydrate metabolism in dogs.

Effects of iloprost, which is a stable prostacyclin analogue, on the ischemic myocardium were examined in the open-chest dog heart in terms of biochemical parameters. Ischemia was initiated by ligating the left anterior descending coronary artery. When the coronary artery was ligated for 3 min, the levels or glycogen, fructose-1,6-diphosphate (FDP), adenosine triphosphate and creatine phosphate decreased, and the levels of glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), lactate, adenosine diphosphate and adenosine monophosphate increased. During ischemia, therefore, energy charge potential was significantly decreased from 0.89 +/- 0.01 to 0.82 +/- 0.01, and ([G6P] + [F6P])/[FDP] and [lactate]/[pyruvate] ratios were significantly increased from 1.75 +/- 0.30 to 29.05 +/- 5.70 and 13 +/- 3 to 393 +/- 112, respectively. Iloprost (0.1, 0.3, or 1 microgram.kg-1) was injected intravenously 5 min before the onset of ischemia. Iloprost (0.1, 0.3, and 1 micrograms.kg-1) reduced the ischemia-induced decrease in energy charge potential to 94, 74, and 86%, respectively, the increase in ([G6P] + [F6P])/[FDP] to 38, 29, 32%, respectively, and the increase in [lactate]/[pyruvate] to 67, 45, 65%, respectively. These results suggest that iloprost lessens the myocardial metabolic derangements produced by ischemia, and the most potent effect was obtained at the dose of 0.3 microgram.kg-1.

Adenosine Diphosphate↗
PubMed1994

Effect of fructose-1,6-bisphosphate on glutamate uptake and glutamine synthetase activity in hypoxic astrocyte cultures.

Astrocytes are important in regulating the microenvironment of neurons both by catabolic and synthetic pathways. The glutamine synthetase (GS) activity observed in astrocytes affects neurons by removing toxic substances, NH3 and glutamate; and by providing an important neuronal substrate, glutamine. This glutamate cycle might play a critical role during periods of hypoxia and ischemia, when an increase in extracellular excitatory amino acids is observed. It was previously shown in our laboratory that fructose-1,6-bisphosphate (FBP) protected cortical astrocyte cultures from hypoxic insult and reduced ATP loss following a prolonged (18-30 hrs) hypoxia. In the present study we established the effects of FBP on the level of glutamate uptake and GS activity under normoxic and hypoxic conditions. Under normoxic conditions, [U-14C]glutamate uptake and glutamine production were independent of FBP treatment; whereas under hypoxic conditions, the initial increase in glutamate uptake and an overall increase in glutamine production in astrocytes were FBP-dependent. Glutamine synthetase activity was dependent on FBP added during the 22 hours of either normoxic- or hypoxic-treatment, hence significant increases in activity were observed due to FBP regardless of the oxygen/ATP levels in situ. These studies suggest that activation of GS by FBP may provide astrocytic protection against hypoxic injury.

Animals↗
PubMed1995

Energy metabolism in hypoxic astrocytes: protective mechanism of fructose-1,6-bisphosphate.

The protective effects of fructose-1,6-biphosphate (FBP) during hypoxia/ischemia are thought to result from uptake and utilization of FBP as a substrate for glycolysis or from stimulation of glucose metabolism. To test these hypotheses, we measured CO2 and lactate production from [6-14C]glucose, [1-14C]glucose, and [U-14C]FBP in normoxic and hypoxic cultured astrocytes with and without FBP present. FBP had little effect on CO2 production by glycolysis, but increased CO2 production by the pentose phosphate pathway. Labeled FBP produced very small amounts of CO2. Lactate production from [1-, and 6-14C]glucose increased similarly during hypoxic hypoxia; the increase was independent of added FBP. Labeled lactate from [U-14C]FBP was minimal. We conclude that exogenous FBP is not used by astrocytes as a substrate for glycolysis and that FBP alters glucose metabolism.

Animals↗
PubMed1994

Hexose diphosphates and phosphofructokinase in rat brain during development.

Fructose 2,6-diphosphate and glucose 1,6-diphosphate concentrations were determined during late gestation and over the course of suckling in rat brain cortex and cerebellum. Cortex fructose 2,6-diphosphate concentration was greatest in neonatal animals and gradually declined thereafter by 25% to reach the adult level at 15 days of age. In contrast, the glucose 1,6-diphosphate concentration increased 4-fold over the same period to reach its highest level by postnatal day 15. Neither cerebellar fructose 2,6-diphosphate nor glucose 1,6-diphosphate concentrations varied significantly. Six day cortex 6-phosphofructo-1-kinase was less sensitive to inhibition by citrate than the enzyme obtained from 15 day pups, and fructose 2,6-diphosphate was better than glucose 1,6-diphosphate at relieving the inhibition imposed by citrate at either age. It is suggested that the rise in cerebral glucose use which occurs during suckling cannot be attributed to either changes in the concentrations of fructose 2,6-diphosphate or glucose 1,6-diphosphate, or the age-related differential sensitivity of 6-phosphofructo-1-kinase toward these effectors.

Animals↗
PubMed1993

Modification of Cys-128 of pig kidney fructose 1,6-bisphosphatase with different thiol reagents: size dependent effect on the substrate and fructose-2,6-bisphosphate interaction.

Treatment of fructose 1,6-bisphosphatase with N-ethylmaleimide was shown to abolish the inhibition by fructose 2,6-bisphosphate, which also protected the enzyme against this chemical modification [Reyes, A., Burgos, M. E., Hubert, E., and Slebe, J. C. (1987), J. Biol. Chem. 262, 8451-8454]. On the basis of these results, it was suggested that a single reactive sulfhydryl group was essential for the inhibition. We have isolated a peptide bearing the N-ethylmaleimide target site and the modified residue has been identified as cysteine-128. We have further examined the reactivity of this group and demonstrated that when reagents with bulky groups are used to modify the protein at the reactive sulfhydryl [e.g., N-ethylmaleimide or 5,5'-dithiobis-(2-nitrobenzoate)], most of the fructose 2,6-bisphosphate inhibition potential is lost. However, there is only partial or no loss of inhibition when smaller groups (e.g., cyanate or cyanide) are introduced. Kinetic and ultraviolet difference spectroscopy-binding studies show that the treatment of fructose 1,6-bisphosphatase with N-ethylmaleimide causes a considerable reduction in the affinity of the enzyme for fructose 2,6-bisphosphate while affinity for fructose 1,6-bisphosphate does not change. We can conclude that modification of this reactive sulfhydryl affects the enzyme sensitivity to fructose 2,6-bisphosphate inhibition by sterically interfering with the binding of this sugar bisphosphate, although this residue does not seem to be essential for the inhibition to occur. The results also suggest that fructose 1,6-bisphosphate and fructose 2,6-bisphosphate may interact with the enzyme in a different way.

Amino Acids↗
PubMed1986

Hormonal control of fructose 2,6-bisphosphate concentration and of phosphofructokinase 2 in the rat liver during development.

In fetal rat liver the concentration of fructose 2,6-bisphosphate is decreased by administration of glucagon. The glucagon effect, i.e., the phosphorylation state of phosphofructokinase 2, dominates over the substrate supply. Insulin was found to increase fructose 2,6-bisphosphate only when exogenous glucose is supplied simultaneously. The total activity of phosphofructokinase 2 exhibits remarkable developmental changes. It is high at term, moderate in the fetal as well as in the mature organ, and low during suckling. The level of the enzyme during development is controlled by pancreatic and adrenal hormones.

Adrenal Cortex Hormones↗
PubMed1990

Kinetic studies of pyruvate kinase during in vitro differentiation of GM-CFC haemopoietic precursor and bone marrow cells in mice.

Pyruvate kinase studies in the granulocyte-macrophage lineage during in vitro differentiation have been performed using culture techniques on GM-CFC cells and a study has also been done in bone marrow cells. The enzyme exhibits biphasic behaviour with respect to both of its substrates in cells derived from in vitro cultures at 5 and 7 days of incubation period. However in bone marrow cells these kinetics are only observed for ADP. The different kinetic behaviour of pyruvate kinase toward Fru-1,6-P2, Ala, Phe and ATP in the three cellular populations allows us to conclude that the expression of pyruvate kinase is associated with the differentiation of these cells.

Adenosine Diphosphate↗
PubMed1988

Sensitivity of fructose-1,6-biphosphatase from yeast, liver and skeletal muscle to fructose-2,6-biphosphate and 5'-adenosine monophosphate.

As a prerequisite for future studies on the possible effect of sulphite, an anti-microbial agent, on gluconeogenesis in yeast, a comparative study of fructose-1,6-bisphosphatase (FBPase), a key enzyme of gluconeogenesis, from yeast, liver and skeletal muscle is reported. In contrast to FBPase from yeast or liver, FBPase from skeletal muscle is approximately 1000-fold more sensitive to inhibition by 5' adenosine monophosphate and 30 to 250-fold less sensitive to inhibition by fructose-2,6-bisphosphate. The kinetic properties of the FBPases, determined by the ratios R(Mg2+/Mn2+) and R (pH 7/9) of the enzyme activities, measured at 10 mM Mg2+ and 2 mM Mn2+ and at pH 7.0 and 9.0, respectively, show a drastic difference between the skeletal muscle and the yeast or liver enzymes. The data support the idea that the enzymes from yeast and liver function in gluconeogenesis, whereas the enzyme from skeletal muscle is involved in other biological functions.

Adenosine Monophosphate↗
PubMed1995

Fructose 2,6-bisphosphate metabolism in Ehrlich ascites tumour cells.

Cancer cell energy metabolism is characterized by a high glycolytic rate, which is maintained under aerobic conditions. In Ehrlich ascites tumour cells, the concentration of fructose 2,6-bisphosphate (Fru-2,6-P2), the powerful activator of 6-phosphofructo-1-kinase, is tenfold increased. The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), synthesizing and degrading Fru-2,6-P2, was characterized. The molecular mass is 120 kDa. The dependence of PFK-2 activity on the substrate concentrations is hyperbolic (Km for Fru-6-P = 0.09 mM; Km for ATP = 0.7 mM), while the dependence of the FBPase-2 activity on the concentrations of Fru-2,6-P2 is sigmoidal (K0.5 for Fru-2,6-P2 = 4 microM). The PFK-2/FBPase-2 activity ratio is 1. PFK-2 activity is inhibited by citrate (I0.5 = 0.17 mM) and phosphoenolpyruvate (I0.5 = 0.08 mM) but only weakly by glycerol 3-phosphate (I0.5 = 1.57 mM). In contrast to the liver enzyme, the activity of tumour PFK-2/FBPase-2 is not influenced by the action of cAMP-dependent protein kinase. The kinetic properties as well as ion-exchange chromatography pattern differ from their normal counterparts in liver and muscle. The properties are likely to contribute to the maintenance of the high glycolytic rate in these tumour cells.

Alkaline Phosphatase↗
PubMed1990

2,3-Bisphosphoglycerate, fructose, 2,6-bisphosphate and glucose 1,6-bisphosphate during maturation of reticulocytes with low 2,3-bisphosphoglycerate content.

In contrast to the species with erythrocytes of high 2,3-bisphosphoglycerate content, in the sheep the concentration of 2,3-bisphosphoglycerate decreases during maturation of reticulocytes. The decrease can be explained by the drop of the phosphofructokinase/pyruvate kinase and 2,3-bisphosphoglycerate synthase/2,3-bisphosphoglycerate phosphatase activity ratios that result from the decline of phosphofructokinase, pyruvate kinase, phosphoglycerate mutase and the bifunctional enzyme 2,3-bisphosphoglycerate synthase/phosphatase. The concentrations of fructose 2,6-bisphosphate and aldohexose 1,6-bisphosphates also decrease during sheep reticulocyte maturation in parallel to the 6-phosphofructo 2-kinase and the glucose 1,6-bisphosphate synthase activities.

2,3-Diphosphoglycerate↗