Of fructose 1,6-diphosphate

The active site also facilitates the ketone-hemiketal interconversion, so that the product liberated is the hemiketal form of fructose 1,6-diphosphate. 

The ozone treatment had no significant effect on the vitro NR activity, indicating that it did not inactivate the NR protein (Table III), Leaf extracts that would couple the oxidation of fructose-1, 6-diphosphate to nitrate reduction were prepared from leaves exposed to either 0 or 980 yg/m ozone ( ), Ozone depressed the in vitro coupled NR activity 58% (Table III), indicating that the observed ozone depression of nitrate reduction in the vivo leaf disk assay resulted from a depression in the rate of NADH formation by GPD,... 

Figure 10.4 The abolition of positive cooperativity on the binding of allosteric effectors to some enzymes. Note the dramatic increases in activity at low substrate concentrations on the addition of adenosine monophosphate to isocitrate dehydrogenase, of deoxycytosine diphosphate to deoxythymidine kinase, and of fructose 1,6-diphosphate to pyruvate kinase this shows how the activity may be switched on by an allosteric effector (PEP = phosphoenolpyruvate). [From J. A. Hathaway and D. E. Atkinson, J. Biol. Chem. 238,2875 (1963) R. Okazaki and A. Kornbcrg, J. Biol. Chem. 239,275 (1964) R. Haeckel, B. Hess, W. Lauterhom, and K.-H. Wurster, Hoppe-Seyler s Z. Physiol. Chem. 349, 699 (1968).]...

At this stage the enzyme aldolase catalyzes the aldol cleavage of fructose 1,6-diphosphate. One product is glyceraldehyde 3-phosphate and the other is... 

The presence in mammalian liver of a specific phosphatase which catalyzes the hydrolysis of fructose 1,6-diphosphate (1) was first reported by Gomori in 1943 ( ). He succeeded in separating the enzyme from other phosphatases present in mammalian tissues and thus clarified much of the confusion which had previously existed regarding the specificity of these phosphatases. The specific fructosediphosphatase (FDPase) was shown to require a divalent cation such as Mg2+ and to be inactive at acid or neutral pH. It was present in the livers and kidneys of a number of mammalian species. 

The hydrolysis of fructose 1,6-diphosphate occurs at the oxygen-phosphorus linkage of the substrate, leading to the formation of l80-labeled inorganic phosphate when the hydrolysis is carried out in Ha180. No evidence for an enzyme-phosphate intermediate could be obtained 22). 

The form of fructose 1,6-diphosphate which is hydrolyzed appears to be the furanoside (Fig. 3), based on the observation of Bencovic and... 

Carbon-carbon bond-forming reactions are some of the most important transformations in organic chemistry. Sobolov et al. [33] reported that CLCs of fructose 1,6-diphosphate aldolase from rabbit muscle are much more stable than the soluble enzyme. The synthetic potential of these CLCs was demonstrated by the preparation of a series of compounds shown in Fig. 10. 

The formation of the Acp after cleavage of fructose 1,6-diphosphate with aldolase (No. 10) corroborates the suggestion that distinct metabolites of the glycolytic pathway are precursors of Acp. 

A reaction involved in the metabolism of sugars is the splitting of fructose- 1,6-diphosphate to give glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. In the living system, this retro-aldol is catalyzed by an enzyme called aldolase however, it can also be catalyzed by a mild base. Propose a mechanism for the base-catalyzed reaction. 

Proton transfers allow this inline to be converted into an enamine, which acts as the nucleophile in the aldol reaction. Stereochemical control (it s a syn aldol) comes from the way in which the two molecules are held by the enzyme as they combine. The product is the imine, which is hydrolysed to the open-chain form of fructose-1,6-diphosphate. 

In vivo, six known DHAP-dependent aldolases are known to catalyze the reversible enanotioselective aldol addition of dihydroxyacetone phosphate to an acceptor aldehyde. The group is comprised of fructose 1,6-diphosphate (FDP) aldolase (EC 4.1.2.13), L-fuculose 1-phosphate (Fuc 1-P) aldolase (EC 4.1.2.17), tagatose 1,6-diphosphate (TDP) aldolase (EC 4.1.2.2), ketotetrose phosphate aldolase (EC 4.1.2.2), L-rhamnulose 1-phosphate (Rha 1-P) aldolase (EC 4.1.2.19), and phospho-5-keto-2-deoxygluconate aldolase (EC 4.1.2.29). The in vivo catalyzed reactions of this group are shown in Scheme 5.3. 

Z8. Zierler, K. L., Levy, R. I., and Andres, R., Dissimilation of glucose-l-phosphate and of fructose-1,6-diphosphate by isolated rat diaphragm and by cell-free effluent from rat diaphragm. Bull. Johns Hopkins Hosp. 92, 7 (1953). 

Bischofberger, N, Waldmann, H, Saito, T, Simon, E S, Lees, W, Bednarski, M D, Whitesides, G M, Synthesis of analogues of 1,3-dihydroxyacetone phosphate and glyceraldehyde 3-phosphate for use in studies of fructose-1,6-diphosphate aldolase, J. Org. Chem., 53, 3457-3465, 1988. 

Ehringer W, Niu W, Chiang B, Wang OL, Gordon L, Chien S (2000) Membrane permeability of fructose-1, 6-diphosphate in lipid... 

Ehringer W, Su S, Chiang B, Stillwell W, Chien S (2002) The membrane destabilizing effects of fructose-1, 6-diphosphate on membrane bilayers. Lipids 37 885-892... 

Ehringer WD, Chiang B, ChienS (2001) The uptake and metabolism of fructose-1, 6-diphosphate in rat cardiomyocytes. Mol Cell Biochem 221 33—10... 

Because LD is present in excess, the rate of NADH oxidation is limited by the activity of PK. The reaction rate is measured by the rate of decrease in absorbance at 340 nm. Assays are performed at low substrate concentration with and without the addition of fructose-1,6-diphosphate, because some PK variants associated with hemolysis have atypical reaction kinetics (and thus may exhibit normal activity at high substrate concentrations but lower than normal activity at lower substrate concentrations) or may show absence of enhancement by fructose-1,6-diphosphate, the allosteric activator of PK. 

Aldolases hold potential for convergent synthesis of fluorocarbohydrates. There have been more than 20 aldolases isolated, eight of which have been explored for organic synthesis. This presentation describes the application of fructose-1,6-diphosphate aldolase, 2-deoxynbose-5-phosphate aldolase and sialic acid aldolase to the synthesis of fluorosugars. 

The enzyme aldolase catalyzes the breakdown of fructose-1, 6-diphosphate and the reverse reaction... 

In our study on the substrate specificity of FDP aldolase, the compound 3-deoxy-3-fluorohydroxyacetone-l-phosphate was found not a substrate for the enzyme it was an inhibitor for the enzymatic cleavage of fructose-1, 6-diphosphate. The was determined to be 3 mM (Figure 4). When sodium borohydride was added to the mixture of aldolase and 3-deoxy-3-fluorohydroxyacetone-l-phosphate, no inactivation of aldolase was observed, indicating that a Schiff base is not formed. The Schiff base intermediate in the mixture of DHAP and aldolase has previously been trapped by reduction with sodium borohydride to inactivate the enzyme (8). The inhibitor may be useful for study of the active site of the enzyme. 

Synthesis of Fructose 1,6-Diphosphate. Production of FDP is another example of the use of our ATP regeneration system. FDP is used as an intravenous therapeutic agent. It is used in resuscitation, total parenteral nutrition, and cardiology. An Italian company produces more than 20 tons of FDP per year by fermentation. The fermentation process... 

Activation by fructose-1, 6-diphosphate offers an attractive possibility for regulation in view of the long-established relationship between glucose utilization and lipogenesis in a number of tissues [87,98,100, 101,244]. The levels of fructose-1, 6-diphosphate are known [245] to vary in the same direction as the rate of fatty acid biosynthesis for example, fructose-1, 6-diphosphate concentration in liver is lower in the fasted and diabetic state, conditions in which fatty acid synthesis is depressed. Further work will be necessary to determine whether activation of the synthetase by sugar phosphates has physiological significance. 

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