Fructose 6-phosphate phosphorylation

Fig. 115 The dependence of the rate of fructose 6-phosphate phosphorylation by phosphofructokinase on the presence of low and high concentrations of ATP.

Glucose and fructose are phosphorylated in the presence of adenosine triphosphate (ATP) in a reaction is catalysed by hexokinase (HK) producing respectively, glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) ... 

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. 

Fructose is phosphorylated by ATP to form fructose 1-phosphate. The enzyme is fructokinase. 

Fructose is phosphorylated primarily in the liver via fructokinase to form fructose-1-phosphate. Fructose can also be phosphorylated by the various hexokinases that catalyze formation of fructose-6-phosphate. However, the Km values of these enzymes for fructose are extremely high, whereas the Km values for glucose are orders of magnitude lower. Therefore, these hexokinases do not catalyze appreciable phosphorylation of fructose, especially in the presence of 5 mM glucose, the normal concentration in blood (Fig. 12.7). 

Fructose metabolism in muscle is illustrated in Fig. 22.2. Fructose is phosphorylated by hcxokina.sc to fructose 6-phosphatc. The fructose 6-phosphate is then used for glycogenesis or, when the glycogen reserves are fuU, energy metabolism via glycolysis. 

Efficient utilization of the fructose requires phosphorylation of the glyceraldehyde. Tracer experiments show that the carbon 1 of fructose appears as both carbons 1 and 6 of glucose. This is the result of triose phosphate isomerization followed by (conventional) aldolase condensation to hexose diphosphate. The conversion of fructose diphosphate to glucose-6-phosphate requires a phosphatase and an isomerase, as discussed in the pentose phosphate pathway. 

In the phosphorylation of fructose by inorganic phosphate and alkaline phosphatase, the major ester formed is stated to be fructose-l-phosphate. Meyerhof and Green have concluded that the 1-phosphate bond possesses less energy than the 6-phosphate bond. Alkaline phosphatase also trans-phosphorylates from creatine phosphate to form the fructose phosphates. ... 

Fructose is metabolized by both fructose hexokinase and PTS (Tonouchi et al. 1996). Fructose is phosphorylated to F6P by hexokinase or to fructose-1-phosphate (FIP) via PTS. F6P is then converted by phosphoglucomutase to G6P, which can subsequently be used for cellulose synthesis or metabolized through the... 

Fructose phosphates are intermediates in the breakdown of glucose according to the Embden-Meyerhof pathway, but free fructose is broken down in a different fashion. At first it is phosphorylated by a fructokinase and ATP to produce/ructose... 

D- rythrose 4-phosphate is a normal intermediate in plant and animal metabolism and is formed by the action of transaldolase and transketolase. An enzyme from acetobacter forms acetyl phosphate and D-erythrose phosphate from fructose 6-phosphate and inorganic phosphate . Phosphorylation of D-erythrose with a bacterial enzyme and ATP or with Jteferenees p. 140... 

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.

Phosphate esters of glucose, fructose, and other monosaccharides are important metabolic intermediates, and the ribose moiety of nucleotides such as ATP and GTP is phosphorylated at the 5 -position (Figure 7.13). 

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. 

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

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. 

Transfer of the phosphoryl group to ADP in step 10 then generates ATP and gives enolpyruvate, which undergoes tautomerization to pyruvate. The reaction is catalyzed by pyruvate kinase and requires that a molecule of fructose 1,6-bis-phosphate also be present, as well as 2 equivalents of Mg2+. One Mg2+ ion coordinates to ADP, and the other increases the acidity of a water molecule necessary for protonation of the enolate ion. 

Functionally related to FruA is the novel class I fructose 6-phosphate aldolase (FSA) from E. coli, which catalyzes the reversible cleavage of fructose 6-phosphate (30) to give dihydroxyacetone (31) and d-(18) [90]. It is the only known enzyme that does not require the expensive phosphorylated nucleophile DHAP for synthetic purpose. 

This reaction is followed by another phosphorylation with ATP catalyzed by the enzyme phosphofructoki-nase (phosphofructokinase-1), forming fructose 1,6-bisphosphate. The phosphofructokinase reaction may be considered to be functionally irreversible under physiologic conditions it is both inducible and subject to allosteric regulation and has a major role in regulating the rate of glycolysis. Fructose 1,6-bisphosphate is cleaved by aldolase (fructose 1,6-bisphosphate aldolase) into two triose phosphates, glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate are inter-converted by the enzyme phosphotriose isomerase. 

Fructose 2,6-bisphosphate is formed by phosphorylation of fructose 6-phosphate by phosphofructoki-nase-2. The same enzyme protein is also responsible for its breakdown, since it has fructose-2,6-hisphos-phatase activity. This hifrmctional enzyme is under the allosteric control of fructose 6-phosphate, which stimulates the kinase and inhibits the phosphatase. Hence, when glucose is abundant, the concentration of fructose 2,6-bisphosphate increases, stimulating glycolysis by activating phosphofructokinase-1 and inhibiting... 

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