Fructose phosphates

Following Its formation D fructose 6 phosphate is converted to its corresponding 1 6 phosphate diester which is then cleaved to two 3 carbon fragments under the mflu ence of the enzyme aldolase... 

Fructose-6-phosphate [643-13-0] M 260.1, [a]o 2.5 (c 3, H2O), pK 5.84. Crystd as the barium salt from water by adding four volumes of EtOH. The barium can be removed by passage through the H" " form of a cation exchange resin and the free acid collected by freeze-drying. 

Figure 6.24 The function of the enzyme phosphofructokinase. (a) Phosphofructokinase is a key enzyme in the gycolytic pathway, the breakdown of glucose to pyruvate. One of the end products in this pathway, phosphoenolpyruvate, is an allosteric feedback inhibitor to this enzyme and ADP is an activator, (b) Phosphofructokinase catalyzes the phosphorylation by ATP of fructose-6-phosphate to give fructose-1,6-bisphosphate. (c) Phosphoglycolate, which has a structure similar to phosphoenolpyruvate, is also an inhibitor of the enzyme.

Fructose-6-phosphate + ATP. fructose-1,6-bisphosphate + ADP + Fructose-1,6-bisphosphate dihydroxyacetoiie-P + glyceraldehyde-3-P Dihydroxyacetoiie-P . glyceraldehyde-3-P ... 

FIGURE 19.9 Fructose-2,6-bisphosphate activates phosphofructokinase, iucreasiug the affinity of the enzyme for fructose-6-phosphate and restoring the hyperbolic dependence of enzyme activity on substrate. 

Fructose-6-phosphate generated in this way enters the glycolytic pathway directly in step 3, the second priming reaction. This is the principal means for channeling fructose into glycolysis in adipose tissue, which contains high levels of fructose. 

Another simple sugar that enters glycolysis at the same point as fructose is mannose, which occurs in many glycoproteins, glycolipids, and polysaccharides (Chapter 7). Mannose is also phosphorylated from ATP by hexokinase, and the mannose-6-phosphate thus produced is converted to fructose-6-phosphate by phosphomannoisomerase. 

The hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate (Eigure 23.7), like all phosphate ester hydrolyses, is a thermodynamically favorable (exergonic) reaction under standard-state conditions (AG° = —16.7 kj/mol). Under physiological conditions in the liver, the reaction is also exergonic (AG = —8.6 kJ/mol). Fructose-1,6-bisphosphatase is an allosterically regulated enzyme. Citrate stimulates bisphosphatase activity, hut fructose-2,6-bisphosphate is a potent allosteric inhibitor. / MP also inhibits the bisphosphatase the inhibition by / MP is enhanced by fructose-2,6-bisphosphate. 

If fructose-1,6-bisphosphatase and phosphofructokinase acted simultaneously, they would constitute a substrate cycle in which fructose-1,6-bisphosphate and fructose-6-phosphate became interconverted with net consumption of ATP ... 

N/ JDPH is considerably greater than the need for ribose-5-phosphate. The next three steps thus return some of the five-carbon units to glyceraldehyde-3-phos-phate and fructose-6-phosphate, which can enter the glycolytic pathway. The advantage of this is that the cell has met its needs for N/VDPH and ribose-5-phosphate in a single pathway, yet at the same time it can return the excess carbon metabolites to glycolysis. 

The transaldolase functions primarily to make a useful glycolytic substrate from the sedoheptulose-7-phosphate produced by the first transketolase reaction. This reaction (Figure 23.35) is quite similar to the aldolase reaction of glycolysis, involving formation of a Schiff base intermediate between the sedohep-tulose-7-phosphate and an active-site lysine residue (Figure 23.36). Elimination of the erythrose-4-phosphate product leaves an enamine of dihydroxyacetone, which remains stable at the active site (without imine hydrolysis) until the other substrate comes into position. Attack of the enamine carbanion at the carbonyl carbon of glyceraldehyde-3-phosphate is followed by hydrolysis of the Schiff base (imine) to yield the product fructose-6-phosphate. 

One of the later steps in glucose biosynthesis is the isomerization of fructose 6-phosphate to glucose 6-phosphate. Propose a mechanism, using acid or base catalysis as needed. 

Mannose, one of the eight essential monosaccharides (Section 25.7), is biosynthesized as its 6-phosphate derivative from fructose 6-phosphate. No enzyme cofactor is required. Propose a mechanism. 

Glucose 6-phosphate is isomerized to fructose 6-phosphate by ring opening followed by a keto-enol tautomerization. 

Fructose 6-phosphate is phosphorylated by reaction with ATP to yield fructose 1,6-bisphosphate. 

Figure 29.8 Mechanism of step 2 in glycolysis, the isomerization of glucose 6-phosphate to fructose 6-phosphate.

Step 3 of Figure 29.7 Phosphorylation Fructose 6-phosphate is converted in step 3 to fructose 1,6-bisphosphate (FBP) by a phosphofmctokinase-catalyzed reaction with ATP (recall that the prefix bis- means two). The mechanism is similar to that in step 1, with Mg2+ ion again required as cofactor. Interestingly, the product of step 2 is the tv anomer of fructose 6-phosphate, but it is the (3 anomer that is phos-phorylated in step 3, implying that the two anomers equilibrate rapidly through the open-chain form. The result of step 3 is a molecule ready to be split into the two three-carbon intermediates that will ultimately become two molecules of pyruvate. 

Hydrolysis of the C1 phosphate group occurs, giving fructose 6-phosphate. . ... 

One of the steps in the pentose phosphate pathway for glucose catabolism is the reaction of sedoheptulose 7-phosphate with glyceraldehyde 3-pho phate in the presence of a transaldolase to yield erythrose 4-phosphate and fructose 6-phosphate. 

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