Fructose 1,6-bisphosphate, cleavage

Although the aldolase reaction has a strongly positive standard free-energy change in the direction of fructose 1,6-bisphosphate cleavage, at the lower concentrations of reactants present in cells, the actual free-energy change is small and the aldolase reaction is readily reversible. We shall see later that aldolase acts in the re-... 

Reaction 4 Cleavage of Fructose-1,6-bisP by Fructose Bisphosphate Aldolase... 

A good example of such a cleavage is the fructose bisphosphate aldolase reaction (see Chapter 19, Figure 19.14a). 

Reaction 2 of Fig. 17-7 is a simple isomerization that moves the carbonyl group to C-2 so that (1 cleavage to two three-carbon fragments can occur. Before cleavage a second phosphorylation (reaction 3) takes place to form fructose 1,6-bisphosphate. This ensures that when fructose bisphosphate is cleaved by aldolase each of the two halves will have a phosphate handle. This second priming reaction (reaction 3) is the first step in the series that is unique to glycolysis. The catalyst for the reaction, phosphofructokinase, is carefully controlled, as discussed in Chapter 11 (see Fig. 11-2). 

In proteins with a symmetric structure, circular permutation can account for the shift of active-site residues over the course of evolution. A very good model of symmetric proteins are the (/Ja)8-barrel enzymes with their typical eightfold symmetry. Circular permutation is characterized by fusion of the N and C termini in a protein ancestor followed by cleavage of the backbone at an equivalent locus around the circular structure. Both fructose-bisphosphate aldolase class I and transaldolase belong to the aldolase superfamily of (a/J)8-symmetric barrel proteins both feature a catalytic lysine residue required to form the Schiff base intermediate with the substrate in the first step of the reaction (Chapter 9, Section 9.6.2). In most family members, the catalytic lysine residue is located on strand 6 of the barrel, but in transaldolase it is not only located on strand 4 but optimal sequence and structure alignment with aldolase class I necessitates rotation of the structure and thus circular permutation of the jS-barrel strands (Jia, 1996). 

D fructose bisphosphate aldolase none aldol cleavage... 

FIGURE 19.13 (a) A mechanism for the fructose-l,6-bisphosphate aldolase reaction. The Schlff base formed between the substrate carbonyl and an active-site lysine acts as an electron sink, Increasing the acidity of the /3-hydroxyl group and facilitating cleavage as shown. (B) In class II aldolases, an active-site Zn stabilizes the enolate Intermediate, leading to polarization of the substrate carbonyl group. 

Step 4 of Figure 29.7 Cleavage Fructose 1,6-bisphosphate is cleaved in step 4 into two 3-carbon pieces, dihydroxyacetone phosphate (DHAP) and glyceraldehvde 3-phosphate (GAP). The bond between C3 and C4 of fructose 1,6-bisphosphate... 

Figure 29.9 Mechanism of step 4 in Figure 29.7, the cleavage of fructose 1,6-bisphosphate to yield glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.

Cleavage of Fructose 1,6-Bisphosphate The enzyme fructose 1,6-bisphosphate aldolase, often called simply aldolase, catalyzes a reversible aldol condensation (p. 485). Fructose 1,6-bisphosphate is cleaved to yield two different triose phosphates, glyceraldehyde 3-phosphate, an aldose, and dihydroxyacetone phosphate, a lcetose ... 

Triose phosphate isomerase interconverts dihydroxyacetone phosphate and glyceraldehyde 3-phosphate (see Figure 8.16). Dihydroxyacetone phosphate must be isomerized to glyceraldehyde 3-phosphate for further metabolism by the glycolytic pathway. This isomerization results in the net production of two molecules of glyceraldehyde 3-phosphate from the cleavage products of fructose 1,6-bisphosphate. 

Write a step-by-step sequence showing the chemical mechanisms involved in the action of a type I aldolase that catalyzes cleavage of fructose 1,6-bisphosphate. The enzyme is inactivated by sodium borohydride in the presence of the substrate. Explain this inactivation. 

Some lactic acid bacteria of the genus Lactobacillus, as well as Leuconostoc mesenteroides and Zymomonas mobilis, carry out the heterolactic fermentation (Eq. 17-33) which is based on the reactions of the pentose phosphate pathway. These organisms lack aldolase, the key enzyme necessary for cleavage of fructose 1,6-bisphosphate to the triose phosphates. Glucose is converted to ribulose 5-P using the oxidative reactions of the pentose phosphate pathway. The ribulose-phosphate is cleaved by phosphoketolase (Eq. 14-23) to acetyl-phosphate and glyceraldehyde 3-phosphate, which are converted to ethanol and lactate, respectively. The overall yield is only one ATP per glucose fermented. 

The metabolic pool that consists of fructose-1,6-bisphosphate and the two triose phosphates—glyceralde-hyde-3-phosphate and dihydroxyacetone phosphate (DHAP)—is somewhat different from the other two pools of intermediates in glycolysis because of the nature of the chemical relationships between these compounds. In the other pools the relative concentrations of the component compounds at equilibrium are independent of the absolute concentrations. Because of the cleavage of one substrate into two products, the relative concentrations of fructose-1,6-bisphosphate and the triose phosphates are functions of the actual concentrations. For such reactions, the relative concentrations of the split products must increase with dilution. (For the reaction A v B + C, the equilibrium constant is equal to [B][C]/[A], If the concentration of A decreases, for example, by a factor of 4, equilibrium is... 

Cleavage of fructose-l,6-bisphosphate, an aldolase-catalyzed reaction. The aldolase reaction entails a reversal of the familiar aldol condensation. The first step involves abstraction of the hydrogen of the C-4 hydroxyl group, followed by elimination of an enolate anion. 

While the lyases that transfer a pyruvate unit form only a single stereogenic center, the group of dihydroxyacetone-phosphate-(DHAP, 41)-dependent aldolases create two new asymmetric centers, one each at the termini of the new C-C bond. A particular advantage for synthetic endeavors is the fact that Nature has evolved a full set of four stereochemically-complementary aldolases [189] (Scheme 6) for the retro-aldol cleavage of diastereoisomeric ketose 1-phosphates— D-fructose 1,6-bisphosphate (42 FruA), D-tagatose 1,6-bisphosphate (43 TagA), L-fuculose 1-phosphate (44 FucA), and L-rhamnulose 1-phosphate (45) aldolase (RhuA). In the direction of synthesis this formally allows the... 

Step 4. Cleavage of Fructose-1,6-Bisphosphate into Three-Carbon Phosphates The reaction is... 

Step 4 is the cleavage of a-D-fructose 1,6-bisphosphate. The reaction, which is reversible, is catalyzed by fructose-1,6-bisphosphate aldolase this enzyme is usually referred to simply as aldolase. 

Cleavage of fructose 1,6-bisphosphate occurs by a reverse aldol reaction. 

The use of aldolases and transketolase has opened the way to many highly multifunctional organic compounds [1]. In organic synthesis, the most widely used dihydroxyacetonephosphate (DHAP) aldolase is the commercially available fruc-tose-1,6-bisphosphate aldolase from rabbit muscle (FruA). This enzyme is a key enzyme of the glycolytic pathway, reversibly catalyzing the cleavage of fructose-... 

Fructose-6-phosphate formed from the isomerization discussed above is further phos-phorylated during glycolysis to fructose-1,6-diphosphate (108), which is then cleaved by fructose-1,6-bisphosphate aldolase to afford dihydroxy acetone phosphate (109) and glyceraldehyde-3-phosphate (110). This cleavage reaction is the reverse of an aldol condensation discussed in Section II.C and during gluconeogenesis. In the latter case, fructose-1,6-bisphosphate aldolase catalyzes the reverse reaction herein via aldol condensation of the ketose 109 and the aldose 110 to form linear fructose-1,6-bisphosphate (108) . 

Fructose 1,6-bisphosphate dihydroxyacetone phosphate + glyceraldehyde 3-phosphate Aldolase Aldol cleavage +5.7 (+23.8) -0.3 (-1.3)... 

Whilst the majority of investigations into halophilic hexose metabolism has been concerned with the catabolism of glucose, it has been recently reported [104,105] that Haloarcula vallismortis catabolises fructose via a modified Embden-Meyerhof pathway. Fructose is phosphorylated to fructose 1-phosphate via a ketokinase, and is then converted to fructose 1,6-bisphosphate via 1-phosphofructokinase. Aldol cleavage generates dihydroxyacetone-phosphate and glyceraldehyde 3-phosphate, both of which can be further metabolised via the glycolytic sequence described earlier. It remains to be established whether other halophilic archaebacteria can also catabolise fructose in this manner. 

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