Genomes and Genes
Summary: Diphosphoric acid esters of fructose. The fructose-1,6- diphosphate isomer is most prevalent. It is an important intermediate in the glycolysis process.
- Riedel B, Gal J, Ellis G, Marangos P, Fox A, Royston D. Myocardial protection using fructose-1,6-diphosphate during coronary artery bypass graft surgery: a randomized, placebo-controlled clinical trial. Anesth Analg. 2004;98:20-9, table of contents pubmed..Preischemic provision of FDP significantly improved cardiac function and reduced perioperative ischemic injury. These myocardial protective effects may improve patient outcome after cardiac surgery. ..
- Leite T, Coelho R, Da Silva D, Coelho W, Marinho Carvalho M, Sola Penna M. Lactate downregulates the glycolytic enzymes hexokinase and phosphofructokinase in diverse tissues from mice. FEBS Lett. 2011;585:92-8 pubmed publisher..PK activity was not affected by lactate. The activity of HK and PFK is directly related to glucose metabolism. Thus, it is conceivable that lactate exposure can induce inhibition of glucose consumption in tissues. ..
- Hua D, Zhuang X, Ye J, Wilson D, Chiang B, Chien S. Using fructose-1,6-diphosphate during hypothermic rabbit-heart preservation: a high-energy phosphate study. J Heart Lung Transplant. 2003;22:574-82 pubmed..This difference was especially prominent in the left and right ventricles. The protective effect of FDP during hypothermic heart preservation deserves further study. ..
- Galzigna L, Rizzoli V, Bianchi M, Rigobello M, Scuri R. Some effects of fructose-1,6-diphosphate on rat myocardial tissue related to a membrane-stabilizing action. Cell Biochem Funct. 1989;7:91-6 pubmed
- Xu Y, Zhao X, Glass D, Absalan F, Perlman D, Broach J, et al. Regulation of yeast pyruvate kinase by ultrasensitive allostery independent of phosphorylation. Mol Cell. 2012;48:52-62 pubmed publisher..Thus, while yeast pyruvate kinase is covalently modified in response to glucose availability, its activity is controlled almost exclusively by ultrasensitive allostery. ..
- Tenenbaum H, Palangio K. Phosphoethanolamine- and fructose 1,6-diphosphate-induced calcium uptake in bone formed in vitro. Bone Miner. 1987;2:201-10 pubmed..The data demonstrate that certain biologically available organic phosphates can induce mineralization and modulate bone metabolism in vitro. ..
- Ma B, Zhang Q, Wang G, Wu Z, Shaw J, Hu Y, et al. Synthesis and pharmacokinetics of strontium fructose 1,6-diphosphate (Sr-FDP) as a potential anti-osteoporosis agent in intact and ovariectomized rats. J Inorg Biochem. 2011;105:563-8 pubmed publisher..The C(max) and AUC(0-?) of Sr-FDP in ovariectomized rats were significantly decreased compared to those in intact rats, and this trend was ameliorated by using 17-beta-estradiol (E(2)) treatment in the ovariectomized rats...
- Bensaad K, Tsuruta A, Selak M, Vidal M, Nakano K, Bartrons R, et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 2006;126:107-20 pubmed..The decrease of intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic damage. ..
- Hitosugi T, Kang S, Vander Heiden M, Chung T, Elf S, Lythgoe K, et al. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal. 2009;2:ra73 pubmed publisher..Our findings suggest that tyrosine phosphorylation regulates PKM2 to provide a metabolic advantage to tumor cells, thereby promoting tumor growth. ..
- Kim T, Keum J, Oh I, Choi C, Kim H, Kim D. An economical and highly productive cell-free protein synthesis system utilizing fructose-1,6-bisphosphate as an energy source. J Biotechnol. 2007;130:389-93 pubmed
- MacDonald M, Al Masri H, Jumelle Laclau M, Cruz M. Oscillations in activities of enzymes in pancreatic islet subcellular fractions induced by physiological concentrations of effectors. Diabetes. 1997;46:1996-2001 pubmed..If this is the case, pacemaker activity may result from complex effects distributed across multiple regulatory sites in both the cytosol and mitochondria, rather than from a single enzyme acting as a primary pacemaker. ..
- Sud V, Lindley S, McDaniel O, Freeland A, Zhang F, Dorsett Martin W, et al. Evaluation of fructose 1,6 diphosphate for salvage of ischemic gracilis flaps in rats. J Reconstr Microsurg. 2005;21:191-6 pubmed..control at the 2.5-hr ischemia period. Further experiments with different modes of FDP administration should be carried out to identify more effective means of amelioration of flap ischemia. ..
- Joshi G, Zianni M, Bobst C, Tabita F. Further unraveling the regulatory twist by elucidating metabolic coinducer-mediated CbbR-cbbI promoter interactions in Rhodopseudomonas palustris CGA010. J Bacteriol. 2012;194:1350-60 pubmed publisher..These in vitro studies suggest that cellular signals such as fluctuating metabolite concentrations are perceived by and transduced to the cbbLS promoter via the master regulator CbbR. ..
- Pawlyk A, Pettigrew D. Subcloning, expression, purification, and characterization of Haemophilus influenzae glycerol kinase. Protein Expr Purif. 2001;22:52-9 pubmed..The possibility of utilizing mutagenesis studies to exploit the high degree of similarity of these two enzymes to elucidate the mechanism of allosteric regulation by IIA(Glc) is discussed. ..
- Francois J, Van Schaftigen E, Hers H. Characterization of phosphofructokinase 2 and of enzymes involved in the degradation of fructose 2,6-bisphosphate in yeast. Eur J Biochem. 1988;171:599-608 pubmed..They have a low affinity for fructose 2,6-bisphosphate (Km greater than 50 microM), are most active at pH 6 and are deeply inhibited by inorganic phosphate and various phosphate esters. ..
- Obach M, Navarro Sabate A, Caro J, Kong X, Duran J, Gomez M, et al. 6-Phosphofructo-2-kinase (pfkfb3) gene promoter contains hypoxia-inducible factor-1 binding sites necessary for transactivation in response to hypoxia. J Biol Chem. 2004;279:53562-70 pubmed..Altogether, these results demonstrate that pfkfb3 is a hypoxia-inducible gene that is stimulated through HIF interaction with the consensus HRE site in its promoter region...
- Holness M, Cook E, Sugden M. Regulation of hepatic fructose 2,6-bisphosphate concentrations and lipogenesis after re-feeding in euthyroid and hyperthyroid rats. A regulatory role for glycogenesis. Biochem J. 1988;252:357-62 pubmed..The response of Fru-2,6-P2 to changes in the glycogenic rate was modified by hyperthyroidism, although a negative correlation was again observed. ..
- Lee Y, Burlet E, Galiano F, Circu M, Aw T, Williams B, et al. Phosphate and succinate use different mechanisms to inhibit sugar-induced cell death in yeast: insight into the Crabtree effect. J Biol Chem. 2011;286:20267-74 pubmed publisher..We propose that succinate depletes matrix phosphate, which in turn inhibits respiration and ATP synthesis. In sum, restoring the Crabtree effect, whether with phosphate or succinate, protects cells from SICD. ..
- Gallego C, Bartrons R, Carreras J. Fructose 2,6-bisphosphate and glucose 1,6-bisphosphate in rabbit erythroid cells during differentiation. FEBS Lett. 1987;222:167-70 pubmed..The enzymatic activities involved in glucose 1,6-bisphosphate metabolism also decrease, but the levels of aldohexose 1,6-bisphosphates remain essentially constant during differentiation of erythroid cells. ..
- Yu P, Pettigrew D. Linkage between fructose 1,6-bisphosphate binding and the dimer-tetramer equilibrium of Escherichia coli glycerol kinase: critical behavior arising from change of ligand stoichiometry. Biochemistry. 2003;42:4243-52 pubmed..5) is due to the approximately 4000-fold higher affinity of the tetramer for FBP rather than to positive coupling between the two FBP sites. ..
- Oh E, Lu M, Park C, Oh H, Lee S, Lee J. Dynamic modeling of lactic acid fermentation metabolism with Lactococcus lactis. J Microbiol Biotechnol. 2011;21:162-9 pubmed..Hexose transporter was the strongest effector on the flux through L-lactate dehydrogenase. The concentration control coefficient (CCC) showed similar results to the flux control coefficient (FCC). ..
- Ding Y, Wang S, Zhang M, Guo Y, Yang Y, Weng S, et al. Fructose-1,6-diphosphate inhibits seizure acquisition in fast hippocampal kindling. Neurosci Lett. 2010;477:33-6 pubmed publisher..Our data demonstrates that FDP has a significant antiepileptogenic effect in kindling seizures and that it may be a potential antiepileptic drug in the future. ..
- Malcovati M, Valentini G. AMP- and fructose 1,6-bisphosphate-activated pyruvate kinases from Escherichia coli. Methods Enzymol. 1982;90 Pt E:170-9 pubmed
- Zorrilla S, Doan T, Alfonso C, Margeat E, Ortega A, Rivas G, et al. Inducer-modulated cooperative binding of the tetrameric CggR repressor to operator DNA. Biophys J. 2007;92:3215-27 pubmed..This bimodal response suggests the existence of two sugar-binding sites in the repressor, a high affinity site at which FBP acts as a structural co-factor and a low affinity site underlying the molecular mechanism of gapA induction. ..
- Guerrero Mendiola C, García Trejo J, Encalada R, Saavedra E, Ramirez Silva L. The contribution of two isozymes to the pyruvate kinase activity of Vibrio cholerae: One K+-dependent constitutively active and another K+-independent with essential allosteric activation. PLoS ONE. 2017;12:e0178673 pubmed publisher..In addition, Western blot analysis indicated that both enzymes were co-expressed. Therefore, it is concluded that VcIPK and VcIIPK contribute to the activity of pyruvate kinase in this ?-proteobacterium. ..
- Wooll J, Friesen R, White M, Watowich S, Fox R, Lee J, et al. Structural and functional linkages between subunit interfaces in mammalian pyruvate kinase. J Mol Biol. 2001;312:525-40 pubmed..These results identify the structural linkages between the Y and Z interfaces in regulating the interconversion of conformational states of rabbit M1-PK. ..
- Fernandez De Mattos S, Alemany V, Aligue R, Tauler A. Increase in Fru-2,6-P(2) levels results in altered cell division in Schizosaccharomyces pombe. Biochim Biophys Acta. 2008;1783:144-52 pubmed..As the key regulators of the cell cycle checkpoints are conserved throughout evolution, these results may help to understand the experimental evidences obtained by manipulation of Fru-2,6-P2 levels in mammalian cells. ..
- Dziewulska Szwajkowska D, Dzugaj A. Kinetic properties of Pelophylax esculentus muscle FBPase. Comp Biochem Physiol B Biochem Mol Biol. 2010;157:294-300 pubmed publisher..In the presence of 0.05-0.5 microM of AMP, K(i) for Fru-2,6P(2) is 92 and 28 nM. I(0.5) for AMP for P. esculentus muscle FBPase is 55 times lower than the corresponding value for P. esculentus liver isozyme. ..
- Sola Penna M, Da Silva D, Coelho W, Marinho Carvalho M, Zancan P. Regulation of mammalian muscle type 6-phosphofructo-1-kinase and its implication for the control of the metabolism. IUBMB Life. 2010;62:791-6 pubmed publisher..The present review integrates recent findings regarding the regulatory aspects of muscle type PFK and discusses their relation to the control of metabolism. ..
- Comino N, Cifuente J, Marina A, Orrantia A, Eguskiza A, Guerin M. Mechanistic insights into the allosteric regulation of bacterial ADP-glucose pyrophosphorylases. J Biol Chem. 2017;292:6255-6268 pubmed publisher..The information reported herein provides exciting possibilities for industrial/biotechnological applications. ..
- Alva N, Carbonell T, Roig T, Bermudez J, Palomeque J. Fructose 1,6 biphosphate administration to rats prevents metabolic acidosis and oxidative stress induced by deep hypothermia and rewarming. Eur J Pharmacol. 2011;659:259-64 pubmed publisher..In addition, we propose that the reduction in extracellular acidosis may be due to improved tissue perfusion during rewarming and that nitric oxide may play a central role. ..
- Martin Sanz P, Cascales M, Bosca L. Fructose 2,6-bisphosphate in isolated foetal hepatocytes. FEBS Lett. 1987;225:37-42 pubmed..These results suggest that an isoenzyme of 6-phosphofructo-2-kinase in foetal hepatocytes different from that of adult hepatocytes may be present. ..
- Kessler R, Schellenberger W, Nissler K, Hofmann E. Binding of fructose 2,6-bisphosphate to yeast phosphofructokinase. Biomed Biochim Acta. 1988;47:221-5 pubmed..Fru-1,6-P2 decreases the affinity of yeast phosphofructokinase to Fru-2,6-P2. The data can be described by assuming either competition of Fru-2,6-P2 and Fru-1,6-P2 for the same binding site or conformationally mediated interactions. ..
- Sola A, De Oca J, Alfaro V, Xaus C, Jaurrieta E, Hotter G. Protective effects of exogenous fructose-1,6-biphosphate during small bowel transplantation in rats. Surgery. 2004;135:518-26 pubmed
- Andralojc P, Keys A, Kossmann J, Parry M. Elucidating the biosynthesis of 2-carboxyarabinitol 1-phosphate through reduced expression of chloroplastic fructose 1,6-bisphosphate phosphatase and radiotracer studies with 14CO2. Proc Natl Acad Sci U S A. 2002;99:4742-7 pubmed..As shown previously, 14C assimilated by photosynthesis was also incorporated into 2-carboxyarabinitol 1-phosphate during subsequent darkness. ..
- Vasta V, Bruni P, Farnararo M. Mechanism of thrombin-induced rise in platelet fructose 2,6-bisphosphate content. Studies using phorbol myristate acetate, dioctanoylglycerol and ionophore A23187. Biochem J. 1987;244:547-51 pubmed..This study suggests that protein kinase C activation and Ca2+ mobilization are both involved in the activation of glycolysis by thrombin. ..
- Tornheim K. Activation of muscle phosphofructokinase by fructose 2,6-bisphosphate and fructose 1,6-bisphosphate is differently affected by other regulatory metabolites. J Biol Chem. 1985;260:7985-9 pubmed..These results are consistent with competition of the two fructose bisphosphates for the same binding site, but indicate that the conformational changes produced by their binding are different. ..
- Galinier A, Deutscher J, Martin Verstraete I. Phosphorylation of either crh or HPr mediates binding of CcpA to the bacillus subtilis xyn cre and catabolite repression of the xyn operon. J Mol Biol. 1999;286:307-14 pubmed..Fructose 1,6-bisphosphate was found to strongly enhance binding of the P-Ser-HPr/CcpA and P-Ser-Crh/CcpA complexes to the xyn cre, but had no effect on binding of CcpA alone. ..
- Ikemoto A, Ueda T. Identification of a nerve ending-enriched 29-kDa protein, labeled with [3-32P]1,3-bisphosphoglycerate, as monophosphoglycerate mutase: inhibition by fructose-2,6-bisphosphate via enhancement of dephosphorylation. J Neurochem. 2003;85:1382-93 pubmed..The significance of these findings is discussed. ..
- Chen Y, Jin X, Tang R, Huang W, Tao Q, Wang B. [Effect of fructose-1,6-diphosphate and dexamethasone on ischemia/reperfusion injury after hemorrhagic shock in rabbits]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2004;16:29-32 pubmed..FDP given during ischemia and DXM could effectively protect the myocardium from reperfusion injury following hemorrhagic shock. ..
- Duran J, Obach M, Navarro Sabate A, Manzano A, Gomez M, Rosa J, et al. Pfkfb3 is transcriptionally upregulated in diabetic mouse liver through proliferative signals. FEBS J. 2009;276:4555-68 pubmed publisher..These results indicate that fructose-2,6-bisphosphate is essential to the maintenance of the glycolytic flux necessary for providing energy and biosynthetic precursors to dividing cells. ..
- Nava S, Fuccella L, Viglianti B. Physiological effects of intravenous fructose 1.6-diphosphate on diaphragmatic function in malnourished patients with COPD. Monaldi Arch Chest Dis. 2004;61:203-8 pubmed
- Zancan P, Almeida F, Faber Barata J, Dellias J, Sola Penna M. Fructose-2,6-bisphosphate counteracts guanidinium chloride-, thermal-, and ATP-induced dissociation of skeletal muscle key glycolytic enzyme 6-phosphofructo-1-kinase: A structural mechanism for PFK allosteric regulation. Arch Biochem Biophys. 2007;467:275-82 pubmed..This conclusion leads to important information about the molecular mechanism by which PFK is regulated by these modulators. ..
- Choe J, Nelson S, Arienti K, Axe F, Collins T, Jones T, et al. Inhibition of fructose-1,6-bisphosphatase by a new class of allosteric effectors. J Biol Chem. 2003;278:51176-83 pubmed..Moreover, the inhibitor could mimic an unknown natural effector of fructose-1,6-bisphosphatase, as it interacts strongly with a conserved residue of undetermined functional significance. ..
- Hines J, Chen X, Nix J, Fromm H, Honzatko R. Structures of mammalian and bacterial fructose-1,6-bisphosphatase reveal the basis for synergism in AMP/fructose 2,6-bisphosphate inhibition. J Biol Chem. 2007;282:36121-31 pubmed..Conceivably, Type I FBPases from all eukaryotes may undergo similar global conformational changes in response to Fru-2,6-P(2) ligation. ..
- Wu C, Okar D, Newgard C, Lange A. Increasing fructose 2,6-bisphosphate overcomes hepatic insulin resistance of type 2 diabetes. Am J Physiol Endocrinol Metab. 2002;282:E38-45 pubmed..These results clearly indicate that increasing hepatic fructose 2,6-bisphosphate overcomes the impairment of insulin in suppressing hepatic glucose production, and it provides a potential therapy for type 2 diabetes. ..
- Bali M, Thomas S. A modelling study of feedforward activation in human erythrocyte glycolysis. C R Acad Sci III. 2001;324:185-99 pubmed
- Skalecki K, Rakus D, Wisniewski J, Kolodziej J, Dzugaj A. cDNA sequence and kinetic properties of human lung fructose(1, 6)bisphosphatase. Arch Biochem Biophys. 1999;365:1-9 pubmed..The synergistic effect of AMP and Fru(2,6)P2 on the lung and liver Fru(1,6)Pase was also observed. In the presence of AMP the corresponding values of Ki for Fru(2,6)P2 were 16 microM for the lung and 10 microM for the liver enzyme. ..
- Feng L, Sun Y, Deng H, Li D, Wan J, Wang X, et al. Structural and biochemical characterization of fructose-1,6/sedoheptulose-1,7-bisphosphatase from the cyanobacterium Synechocystis strain 6803. FEBS J. 2014;281:916-26 pubmed publisher..Our studies provide insight into the evolution of this enzyme family, and may help in the design of inhibitors aimed at preventing toxic cyanobacterial blooms. ..
- Schumacher M, Seidel G, Hillen W, Brennan R. Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose 6-phosphate and fructose 1,6-bisphosphate. J Mol Biol. 2007;368:1042-50 pubmed
- Seidel G, Diel M, Fuchsbauer N, Hillen W. Quantitative interdependence of coeffectors, CcpA and cre in carbon catabolite regulation of Bacillus subtilis. FEBS J. 2005;272:2566-77 pubmed..Maximal HPrSerP-CcpA-cre complex formation in the presence of 10 mm FBP requires about 10-fold less HPrSerP. These data suggest a specific role for FBP and Glc6-P in enhancing only HPrSerP-mediated CCR. ..
- Okar D, Manzano A, Navarro Sabate A, Riera L, Bartrons R, Lange A. PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate. Trends Biochem Sci. 2001;26:30-5 pubmed..Moreover, the metabolic role of fructose-2,6-bisphosphate has great potential in the treatment of diabetes. ..
- Novellasdemunt L, Tato I, Navarro Sabate A, Ruiz Meana M, Méndez Lucas A, Perales J, et al. Akt-dependent activation of the heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB2) isoenzyme by amino acids. J Biol Chem. 2013;288:10640-51 pubmed publisher..Taken together, these results demonstrate that amino acids stimulate Fru-2,6-P2 synthesis by Akt-dependent PFKFB2 phosphorylation and activation and show how signaling and metabolism are inextricably linked. ..