Treatment of head injury in mice, using a fructose 1,6-diphosphate and dimethyl sulfoxide combination.
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Animals↗
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Results for “Fructosediphosphates”
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Propylene glycol toxicity following continuous etomidate infusion for the control of refractory cerebral edema.
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Acidosis, Lactic↗
Storage solution containing fructose-1,6-bisphosphate inhibits the excess activation of Kupffer cells in cold liver preservation.
BACKGROUND: In liver transplantation, the activation of Kupffer cells at the time of cold preservation and reperfusion is considered to play an important role. In the present study, the usefulness of cold storage solution containing fructose-1,6-bisphosphate (FBP) was compared with University of Wisconsin (UW) solution in the function of Kupffer cells. METHODS: Kupffer cells were separated from rat liver stored at 4 degrees C in each storage solution. Four kinds of storage solutions were used: UW, simplified UW without FBP (0-FBP), and solutions with 10 or 20 mM FBP (10-FBP, 20-FBP). Lipopolysaccharide (LPS) labeled by fluorescein was loaded after 12 or 24 hr of cold preservation in each solution. The rates of cells uptaking LPS as phagocytic ability were measured using flow cytometry. Tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and nitric oxide (NO) were measured in the supernatant. RESULTS: Tumor necrosis factor-alpha values in the 20-FBP group were significantly lower than those in the UW group. Cytokine-induced neutrophil chemoattractant values at 60 min after loading LPS were significantly lower in the 20-FBP group than in the UW group. NO values at 24 hr after loading LPS were significantly lower in the 20-FBP group compared with the UW group. The 20-FBP group was highest in the rates of cells uptaking LPS after 24-hr cold preservation. CONCLUSIONS: The storage solution containing FBP controlled the secretion of cytokines and NO from Kupffer cells and maintained phagocytic ability. This solution was considered to be more useful than UW solution for Kupffer cell protection.
Adenosine↗
Fructose-1,6-diphosphate alone and in combination with cyclosporine potentiates rat cardiac allograft survival and inhibits lymphocyte proliferation and interleukin-2 expression.
BACKGROUND: Fructose-1,6-diphosphate (FDP) reduces postischemic reperfusion injury and is used alone and in combination with cyclosporine A (CsA) as an immunosuppressant. METHODS: Wistar-Furth rat hearts were grafted to Lewis rats. Activated T-cell proliferation, viability, and interleukin-2 expression were determined. RESULTS: Mean survival in days were: saline 7.12+/-0.64, FDP 350 mg/kg perioperatively 13.5+/-1.4, FDP 350 mg/kg twice daily 11.4+/-0.75, CsA 2.5 mg/kg daily 12+/-0.81, CsA 5.0 mg/kg daily 12.4+/-0.81, CsA 2.5 mg/kg + FDP 350 mg/kg twice daily 17.6+/-0.4, and CsA 5 mg/kg + FDP 350 mg/kg twice daily 28.2+/-0.97. FDP maximally inhibits T-cell proliferation and concomitantly increases cell viability at 5,000 to 500 microg/mL, whereas CsA inhibits at 500 ng/mL. FDP completely inhibited interleukin-2 expression at 5,000 to 500 microg/mL, whereas CsA partially inhibited at 50 to 500 ng/mL. CONCLUSION: FDP + CsA prolongs cardiac survival and FDP inhibits T-cell proliferation.
Animals↗
Clinical and pharmaceutical management of deficiencies, excesses and infection with nutrition support.
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Bacterial Infections↗
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: suiting structure to need, in a family of tissue-specific enzymes.
The present review addresses recent advances in research into a family of bifunctional enzymes that are responsible for the twofold task of synthesizing and hydrolyzing fructose-2,6-bisphosphate (Fru-2,6-P2), which in turn regulates the rate of glycolysis in most cells. The structure of the synthetic kinase, conjoined at its carboxyl-terminus to the phosphatase, is very highly conserved throughout evolution and differentiation, with isotypic expression arising from highly variable amino-terminal and carboxyl-terminal regulatory domains. These domains, which frequently contain protein-kinase-catalyzed phosphorylation motifs, are responsible for the widely divergent kinetics observed in various tissues and species, and for the hormonal modulation that alters intracellular levels of Fru-2,6-P2. The present review discusses recent advances in relating structure to function, and the identification of new pathways of transcriptional regulation of this important family of regulatory enzymes.
Adrenal Cortex Hormones↗
Apoptosis inhibition during preservation by fructose-1,6-diphosphate and theophylline in rat intestinal transplantation.
OBJECTIVE: This study evaluated the effect of fructose-1,6-diphosphate (FDP), theophylline, or the addition of both together to the preservation solution (University of Wisconsin [UW]) on apoptosis during preservation and the effect of apoptosis minimization on the early reperfusion period after transplantation. DESIGN: Prospective, randomized, and controlled animal study. SETTING: Laboratory of a research institute. SUBJECT: Male Wistar rats. INTERVENTIONS: The jejunum was isolated and preserved for 6 hrs in UW solution. FDP and theophylline were added to the UW solution to evaluate their effects on apoptosis both alone and together. The role of adenosine with respect to FDP was examined by increasing endogenous adenosine. In addition, rats were subjected to intestinal transplantation for the evaluation of the effect of apoptosis on bacterial translocation, histology, and neutrophil infiltration after reperfusion. MEASUREMENTS AND MAIN RESULTS: Caspase-3 activity, assayed both in vitro or by cleaved caspase-3 levels in Western blots or immunohistochemically, and the number of terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling (TUNEL)-positive cells decreased with FDP and with theophylline addition to UW solution. Increase of endogenous adenosine reversed the antiapoptotic effect of FDP. FDP and theophylline together demonstrated a more pronounced antiapoptotic effect and prevented bacterial translocation after transplantation. CONCLUSION: Supplementary FDP to UW solution decreased apoptosis through an adenosine-independent mechanism. Addition of theophylline to UW solution decreased both apoptosis and bacterial translocation. Concomitant theophylline and FDP addition to preservation solution is recommended to maintain low levels of apoptosis during intestinal hypothermic preservation and to decrease bacterial translocation.
Adenosine↗
Fructose 1,6-bisphosphate prevented endotoxemia, macrophage activation, and liver injury induced by D-galactosamine in rats.
OBJECTIVE: Fructose 1,6-bisphosphate (F1,6BP) protects organs against a wide range of challenges involving inflammation. We hypothesized that the primary action of F1,6BP is to prevent macrophage activation and cytokine release. Our aim was to determine the tissue and cellular targets for this bisphosphorylated sugar and to provide new insights into its mechanisms of action. DESIGN: Prospective, controlled laboratory study. SETTING: Animal resource facilities and research laboratory. SUBJECTS: Male Sprague-Dawley rats (200-250 g body weight). INTERVENTIONS: The protective action of F1,6BP was analyzed in galactosamine (GalN)-induced hepatitis in rats. The in vivo effects of F1,6BP were evaluated by changes in transaminase activities, blood endotoxins, and tumor necrosis factor (TNF)-alpha production in GalN-challenged rats. The targets of F1,6BP to reduce macrophage response to lipopolysaccharide (LPS) were determined by correlation between changes in TNF-alpha production and K+ fluxes through cell membrane in primary cultures of Kupffer cells. MEASUREMENTS AND MAIN RESULTS: The in vivo results indicate that F1,6BP treatment prevented GalN-induced injury in liver parenchymal cells. This protection was mainly associated with a reduction of the inflammatory response. F1,6BP prevention of GalN-induced endotoxemia correlated with preclusion of mast cell degranulation and histamine release that preceded the increased plasma endotoxins and liver production of TNF-alpha. In addition, F1,6BP treatment decreased sensitivity to LPS, which reduced the GalN-induced increase in TNF-alpha. The in vitro results show that F1,6BP inhibited Kupffer cell response and reduced TNF-alpha production by preventing LPS-induced K+ channel activation. CONCLUSIONS: The role of exogenous F1,6BP as a K+ channel modulator underlies its antihistaminic and anti-inflammatory action and increases its interest as a protective compound.
Analysis of Variance↗
Multiple beneficial actions of fructose 1,6-biphosphate in sepsis-associated liver injury.
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Animals↗
The control of glycolysis and gluconeogenesis by protein phosphorylation.
Fructose 2,6-bisphosphate has been discovered as a potent stimulator of liver phosphofructokinase. It is also an inhibitor of fructose 1,6-biphosphatase and a stimulator of PPi: fructose 6-phosphate phosphotransferase from higher plants. It is formed from fructose 6-phosphate and ATP by a 6-phosphofructo 2-kinase and hydrolysed by a fructose 2,6-bisphosphatase. These two enzymes have very similar physicochemical properties and could not be separated from each other. They are substrates for cyclic-AMP-dependent protein kinase, which inactivates the first enzyme and activates the second.
Animals↗
Lactosphaera gen. nov., a new genus of lactic acid bacteria, and transfer of Ruminococcus pasteurii Schink 1984 to Lactosphaera pasteurii comb. nov.
The phylogenetic position and physiology of strain KoTa2T (T = type strain), which was previously classified as a Ruminococcus pasteurii strain, were studied. A determination of the 16S ribosomal DNA sequence of this taxon revealed its position within the radiation of the gram-positive lactic acid bacteria having low DNA G+C contents and that it is closely related to the genus Carnobacterium. L-Lactic acid was produced from glucose by a fructose-1,6-bisphosphate-activated lactate dehydrogenase, and oxygen tolerance was observed, characteristics which are consistent with assignment to this group. On the basis of its phenotypic characteristics and unique signature nucleotides, we propose that strain KoTa2 (= DSM 2381 = ATCC 35945) should be transferred to a new genus, Lactosphaera gen. nov., as the type strain of the species Lactosphaera pasteurii comb. nov.
Anaerobiosis↗
Fructose 2,6-bisphosphate and carbohydrate metabolism during the life cycle of the aquatic fungus Blastocladiella emersonii.
Removal of the growth medium and resuspension of Blastocladiella emersonii vegetative cells in a sporulation medium resulted in an abrupt fall of fructose 2,6-bisphosphate concentration to about 2% of its initial value within 10 min. The concentrations of hexose 6-phosphate and of fructose 1,6-bisphosphate also decreased by, respectively, three and tenfold over the same period. All these values remained at their low level throughout the sporulation phase and during the subsequent germination of zoospores when performed in the absence of glucose. In contrast, the concentration of cyclic AMP was low during the sporulation period and exhibited a transient increase a few minutes after the initiation of germination. Other biochemical events occurring during sporulation were a 70% reduction in glycogen content and the complete disappearance of trehalose. The remaining glycogen was degraded upon subsequent germination of the zoospores. B. emersonii phosphofructo 2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2) could not be separated from each other by various chromatographic procedures, suggesting that they were part of a single bifunctional protein. On anion-exchange chromatography, two peaks of PFK-2 and FBPase-2 were resolved. Upon incubation of fractions from the two peaks or of a crude extract in the presence of [2-32P]fructose 2,6-bisphosphate, two radiolabelled subunits with molecular masses close to 90 and 54 kDa were obtained. The labelling of the subunit of higher molecular mass was greater than that of the lower one in extracts prepared in the presence of protease inhibitors and in the first peak of the Mono Q column. PFK-2 and FBPase-2 displayed kinetic properties comparable to those of mammalian enzymes, but no indication of a cyclic AMP-dependent regulation could be obtained. Phosphofructo 1-kinase and fructose-1,6-bisphosphatase from B. emersonii were, respectively, stimulated and inhibited by micromolar concentrations of fructose 2,6-bisphosphate. The physiological significance of these properties is discussed. A simple method for the determination of trehalose is also reported.
Blastocladiella↗
Characterization of phosphofructokinase II and regulation of fructose 2,6-bisphosphate levels in Trichoderma reesei.
Phosphofructokinase II (PEK II) from Trichoderma reesei was partially purified (247-fold). The calculated Km values for fructose 6-phosphate and ATP were 0.7 mM and 40 microM, respectively. Upon incubation in the presence of [gamma-32P]ATP, the enzyme formed a radioactive phosphoprotein with molecular mass of 67 kDa in autoradiography analysis after SDS-PAGE. Upon incubation in the presence of ATP-Mg and the catalytic subunit of cAMP-dependent protein kinase, its activity was not modified. The same result was obtained when a cell-free extract of T. reesei was incubated with ATP-Mg and cAMP. 2,4-Dinitrophenol caused a transient rise in cAMP levels in the fungal cell. The results provide evidence that the fructose 2,6-bisphosphate level in T. reesei is independent of cAMP concentrations and not related to a cAMP-dependent mechanism, but to the availability of substrate fructose 6-phosphate.
2,4-Dinitrophenol↗
Inactivation of the CDC25 gene product in Saccharomyces cerevisiae leads to a decrease in glycolytic activity which is independent of cAMP levels.
In the budding yeast Saccharomyces cerevisiae cyclic AMP (cAMP) can influence the activity of key enzymes in carbohydrate metabolism through modulation of the activity of cAMP-dependent protein kinase. One of the components involved in cAMP production is the CDC25 gene product, which can activate the RAS/adenylate cyclase pathway by promoting the exchange of guanine nucleotides bound to RAS. In two yeast strains carrying different thermosensitive alleles of the CDC25 gene, cAMP levels respond differently to an increase in growth temperature from 23 degrees C (permissive) to 36 degrees C (restrictive). In strain OL86 (cdc25-5) the estimated intracellular concentration of cAMP dropped after transfer to restrictive temperature whereas in strain ts321 (cdc25-1) the cAMP level rose under the same conditions. Despite the differences in cAMP levels the glycolytic flux in the two mutants responded in a very similar way to the shift from permissive to restrictive temperature; after the increase in the incubation temperature, the specific glycolytic flux in both cdc25-1 and cdc25-5 initially increased from about 300 nmol min-1 (mg protein)-1 to about 500 nmol min-1 (mg protein)-1 (presumably mainly as a consequence of the increase in temperature), but then gradually fell to 100-200 nmol min-1 (mg protein)-1. A similar pattern of CO2 production to that found in the two cdc25 mutants was also observed for several other thermosensitive mutants displaying a Start-II type of G1 arrest. In contrast, in a wild-type strain and in strains giving a Start-I type of G1 arrest, CO2 production did not drop after a temperature shift. The specific activities of glycolytic enzymes in the two cdc25 mutants did not show much change after the temperature shift, indicating that the decrease in glycolytic flux was not caused by a decrease in the activity of any of the glycolytic enzymes. Our data show that, at least in long-term regulation, the cAMP levels per se are not likely to be a prime factor controlling glycolytic flux.
Alleles↗
Mutant studies of phosphofructo-2-kinases do not reveal an essential role of fructose-2,6-bisphosphate in the regulation of carbon fluxes in yeast cells.
The effect of the allosteric regulator fructose-2,6-bisphosphate (F2,6bP) on the regulation of carbohydrate metabolism was investigated in vivo with Saccharomyces cerevisiae mutants containing no, very high or unregulated 6-phosphofructo-2-kinase activity. Simultaneous overproduction of F2,6bP and 6-phosphofructo-1-kinase activity did not increase the glycolytic flux to ethanol. Overexpression of fructose-1,6-bisphosphatase during growth on glucose in a mutant strain devoid of F2,6bP did not cause pronounced effects on the cells. Moreover, high levels of F2,6bP during growth on ethanol in a strain with a highly active 6-phosphofructo-2-kinase enzyme did not affect either carbon flux to glycogen or growth rate. Site-directed mutagenesis of 6-phosphofructo-2-kinase (Pfk26) revealed that serine 644 is involved in the activation of Pfk26 by protein kinase A phosphorylation, but that, additionally, the enzyme can be further activated by phosphorylation of another amino acid residue. The results demonstrate that F2,6bP is not needed to sustain an adequate glycolytic flux under fermentative conditions, but rather is concerned with the homeostasis of metabolite concentrations. Moreover, they fail to indicate a physiological significance for inhibition of fructose-1,6-bisphosphatase by F2,6bP.
Allosteric Regulation↗
Genetic manipulation of 6-phosphofructo-1-kinase and fructose 2,6-bisphosphate levels affects the extent to which benzoic acid inhibits the growth of Saccharomyces cerevisiae.
The mechanisms by which the weak acid preservative benzoic acid inhibits the growth of Saccharomyces cerevisiae have been investigated. A reduction in the pyruvate kinase level, which decreases glycolytic flux, did not increase the sensitivity of yeast to benzoic acid. However, a decrease in 6-phosphofructo-1-kinase (PF1K), which does not affect glycolytic flux, did increase sensitivity to benzoic acid. Also, resistance was increased by elevating PF1K levels. Hence, resistance to benzoic acid was not dependent upon optimum glycolytic flux, but upon an adequate PF1K activity. Benzoic acid was shown to depress fructose 2,6-bisphosphate levels in YKC14, a mutant with low PF1K levels. This effect was partially suppressed by overexpressing constitutively active 6-phosphofructo-2-kinase (Pfk26(Asp644)) or by inactivating fructose-2,6-bisphosphatase (in a Deltafbp26 mutant). The inactivation of PF2K (in a Deltapfk26 Deltapfk27 mutant) increased benzoic acid sensitivity. Therefore, the antimicrobial effects of benzoic acid can be relieved, at least in part, by the genetic manipulation of PF1K or fructose 2,6-bisphosphate levels.
Antifungal Agents↗
Metabolic flux analysis of Escherichia coli in glucose-limited continuous culture. II. Dynamic response to famine and feast, activation of the methylglyoxal pathway and oscillatory behaviour.
The metabolic dynamics of the Escherichia coli K-12 strain TG1 to feast and famine were studied in glucose-limited steady-state cultures by up- and downshifts of the dilution rate, respectively. An uncoupling of anabolic and catabolic rates was observed upon dilution rate upshifts, apparent through immediately increased glucose uptake rates which were not accompanied by an immediate increase of the growth rate but instead resulted in the temporary excretion of methylglyoxal, D- and L-lactate, pyruvate and, after a delay, acetate. The energetic state of the cell during the transient was followed by measuring the adenylate energy charge, which increased within 2 min after the upshift and declined thereafter until a new steady-state level was reached. In the downshift experiment, the adenylate energy charge behaved inversely; no by-products were formed, indicating a tight coupling of anabolism and catabolism. Both dilution rate shifts were accompanied by an instantaneous increase of cAMP, presaging the subsequent changes in metabolic pathway utilization. Intracellular key metabolites of the Embden-Meyerhof-Parnas (EMP) pathway were measured to evaluate the metabolic perturbation during the upshift. Fructose 1,6-diphosphate (FDP) and dihydroxyacetone phosphate (DHAP) increased rapidly after the upshift, while glyceraldehyde 3-phosphate decreased. It is concluded that this imbalance at the branch-point of FDP induces the methylglyoxal (MG) pathway, a low-energy-yielding bypass of the lower EMP pathway, through the increasing level of DHAP. MG pathway activation after the upshift was simulated by restricting anabolic rates using a stoichiometry-based metabolic model. The metabolic model predicted that low-energy-yielding catabolic pathways are utilized preferentially in the transient after the upshift. Upon severe dilution rate upshifts, an oscillatory behaviour occurred, apparent through long-term oscillations of respiratory activity, which started when the cytotoxic compound MG reached a threshold concentration of 1.5 mg l(-1) in the medium.
Bacterial Proteins↗
Proton transport in maize tonoplasts supported by fructose-1,6-bisphosphate cleavage. Pyrophosphate-dependent phosphofructokinase as a pyrophosphate-regenerating system.
The energy derived from pyrophosphate (PPi) hydrolysis is used to pump protons across the tonoplast membrane, thus forming a proton gradient. In a plant's cytosol, the concentration of PPi varies between 10 and 800 microm, and the PPi concentration needed for one-half maximal activity of the maize (Zea mays) root tonoplast H+-pyrophosphatase is 30 microm. In this report, we show that the H+-pyrophosphatase of maize root vacuoles is able to hydrolyze PPi (Reaction 2) formed by Reaction 1, which is catalyzed by PPi-dependent phosphofructokinase (PFP): Fructose-1,6-bisphosphate (F1,6BP) + Pi <--> PPi +Fructose-6-phosphate (F6 P) (reaction 1) PPi --> 2 Pi (reaction 2) H+cyt --> H+vac (reaction 3) F1,6BP + H+cyt <--> H+vac + F6P + Pi (reaction 4) During the steady state, one-half of the inorganic phosphate released (Reaction 4) is ultimately derived from F1,6BP, whereas PFP continuously regenerates the pyrophosphate (PPi) hydrolyzed. A proton gradient (DeltapH) can be built up in tonoplast vesicles using PFP as a PPi-regenerating system. The Delta pH formed by the H+-pyrophosphatase can be dissipated by addition of 20 mm F6P, which drives Reaction 1 to the left and decreases the PPi available for the H+-pyrophosphatase. The maximal Delta pH attained by the pyrophosphatase coupled to the PFP reaction can be maintained by PFP activities far below those found in higher plants tissues.
Biological Transport↗